H A N D B O O K O F OBESITY T R E A T M E N T
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Edited b y
Thomas A. Wadden A l b e r t J. S t u n k a r d
The Guilford Press N e w York London
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© 2002 The Guilford Press A Division of Guilford Publications, Inc. 72 Spring Street, N e w York, N Y 10012 www.guilford.com All rights reserved Paperback edition 2004 No part of this book may be reproduced, translated, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher. Printed in the United States of America This book is printed on acid-free paper. Last digit is print number: 9 8 7 6 5 4 3
Library of Congress Cataloging-in-Publication Data Handbook of obesity treatment / edited by Thomas A. Wadden, Albert J. Stunkard. p. cm. Updated ed. The 2nd ed. was previously published as: Obesity : theory and therapy. Includes bibliographical references and index. ISBN 1-57230-722-6 (he.) ISBN 1-59385-094-8 (pbk.) 1. Obesity. I. Wadden, Thomas A. II. Stunkard, Albert J., 1922- III. Obesity. RC628 .032 2001 616.3'98—dc21
2001040507
For David, Michael, a n d Steven a n d for Elana with deepest love a n d affection
A b o u t
the
Editors
T h o m a s A. W a d d e n , P h D , is Professor of Psychology at the University of Pennsylvania School of Medicine, where he also is Director of the Weight and Eating Disorders Program. H e received his A B from Brown University and his doctorate in clinical psychology from the University of North Carohna at Chapel Hdl. Dr. W a d d e n has published over 150 scientific papers and is the coeditor of two books. H e has investigated the treatment of obesity by several methods, including behavior modification, very-low-calorie diets, exercise, pharmacotherapy, and surgery. H e serves on the National Task Force for the Prevention and Treatment of Obesity and on the Council of the North American Association for the Study of Obesity. Albert J. Stunkard, MD, is Professor of Psychiatry at the University of Pennsylvania School of Medicine where, in 1957, he founded the Obesity Research Group (now the Weight and Eating Disorders Program). H e received his BS from Yale University and his M D from Columbia University. Dr. Stunkard is the author of nearly 400 publications, primarily in the field of obesity, and his research has been supported for 4 0 years by the National Institutes of Health. H e is a m e m b e r of the Institute of Medicine and serves on the editorial boards of seven journals in the fields of nutrition and behavioral medicine.
VI
Contributors
Drew A. Anderson, PhD, Department of Psychology, State University of N e w York at Albany, Albany, N Y Louis J. Aronne, M D , Department of Medicine, Weill College of Cornell University, N e w York, N Y Richard L. Atkinson, M D , Department of Medicine and Nutritional Sciences and Beers-Murphy Clinical Nutrition Center, University of Wisconsin, Madison, W I Joaquin Barnoya, M D , Department of Nutrition, Harvard School of Public Health, Boston, M A Robert L Berkowitz, M D , Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, P A Steven N . Blair, P E D , The Cooper Institute, Dallas, T X George A. Bray, M D , Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, L A Kelly D. Brownell, PhD, Department of Psychology, Yale University, N e w Haven, C T Streamson C. Chua, Jr., M D , PhD, Division of Molecular Genetics, Department of Pediatrics, Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, N e w York, N Y Graham A. Colditz, M D , DrPH, Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, M A Zafra Cooper, DPhil, DipClinPsych, Department of Psychiatry, Oxford University, Oxford, England Joyce A. Corsica, PhD, Department of Clinical and Health Psychology, University of Florida, Gainesville, FL Eric J. D e Maria, M D , Department of Surgery, Medical College of Virginia at Virginia C o m m o n wealth University, Richmond, V A Johanna Dwyer, DSc, R D , Jean Mayer H u m a n Nutrition Center on Aging and Tufts University Schools of Medicine and Nutrition, Boston, M A ; Frances Stern Nutrition Center, N e w England Medical Center, Boston, M A Leonard H . Epstein, PhD, Department of Pediatrics, State University of N e w York at Buffalo, Buffalo,
NY Christopher G. Fairburn, D M , FRCPsych, Department of Psychiatry, Oxford University, Oxford, England Alison E. Field, ScD, Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, M A Gary D. Foster, PhD, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, P A Gary S. Goldfield, PhD, Department of Psychology, State University of N e w York at Buffalo, Buffalo,
NY Edward W . Gregg, PhD, Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Adanta, G A Katherine Batde Horgen, PhD, Department of Psychology, Yale University, N e w Haven, C T
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Contributors
Robert W. Jeffery, PhD, Division of Epidemiology, University of Minnesota, Minneapolis, MN Carol Johnson, M A , Largely Positive, Incorporated, Milwaukee, W I John M . Kellum, M D , Department of Surgery, Medical College of Virginia at Virginia C o m m o n wealth University, Richmond, V A Shiriki K. Kumanyika, PhD, M P H , R D , Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, P A Rifat Latifi, M D , Department of Surgery, Medical College of Virginia at Virginia Commonwealth University, Richmond, V A Elizabeth A. Leermakers, PhD, The Cooper Institute, Dallas, T X Rudolph L. Leibel, M D , Division of Molecular Genetics, Department of Pediatrics, N a o m i Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, N e w York, N Y Brian G. McGuckin, E d M , Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, P A Kathleen Melanson, PhD, R D , L D , Department of Nutrition and Food Sciences, University of Rhode Island, Kingston, Rl Suzette Osei, M D , PhD, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, P A Michael G. Perri, PhD, Department of Clinical and Health Psychology, University of Florida, Gainesville, FL Suzanne Phelan, PhD, Weight Control and Diabetes Research Center, Miriam Hospital, and Department of Psychiatry and H u m a n Behavior, Brown University Medical School, Providence, R L R. Arlen Price, PhD, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA Eric Ravussin, PhD, Pennington Biomedical Research Institute, Baton Rouge, L A HoUie A. Raynor, M S , R D , Department of Psychology, State University of N e w York at Buffalo, Buffalo, N Y David B. Sarwer, PhD, Departments of Psychiatry and Surgery and The Edwin and Fannie Gray Hall Center for H u m a n Appearance, University of Pennsylvania School of Medicine, Philadelphia, P A Kathryn H. Schmitz, PhD, M P H , Division of Epidemiology, University of Minnesota, Minneapolis,
MN Albert J. Stunkard, M D , Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, P A Harvey J. Sugerman, M D , Department of Surgery, Medical College of Virginia at Virginia C o m m o n wealth University, Richmond, V A P. A. Tataranni, M D , National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Tucson, A Z J. Kevin Thompson, PhD, Department of Psychology, University of South Florida, Tampa, FL Thomas A. Wadden, PhD, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, P A Shirley S. W a n g , Department of Psychology, Yale University, N e w Haven, C T David F. Williamson, PhD, Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, G A Rena R. Wing, PhD, Weight Control and Diabetes Research Center, Miriam Hospital, and Department of Psychiatry and H u m a n Behavior, Brown University Medical School, Providence, Rl Leslie G. Womble, PhD, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, P A
Preface
The past decade has witnessed unprecedented interest in the topic of obesity. T h e discovery in 1994 of the ob/ob gene and its protein product, leptin, will long remain a watershed mark in the history of obesity research, revealing as it did key mechanisms of body weight regulation. This discovery came at an opportune time, for other research completed the same year revealed that the United States w a s experiencing an epidemic of obesity. Fully 5 5 % of adults were found to be either overweight or obese. Data from 1999 found that the prevalence had increased to 6 1 % , placing overweight/obesity a m o n g our nation's most pressing public health problems. Regrettably, this problem is shared with growing numbers of developed nations—a fact that has led the World Health Organization to declare obesity a "global epidemic." This volume seeks to improve the treatment of obesity by providing practitioners with a thorough review of its assessment and of therapies available to manage it. Particular attention is paid to identifying the most appropriate intervention for a given individual. T h e book also seeks to illuminate the causes of the obesity epidemic, with the ultimate goal of identifying innovative strategies to prevent the development of this disorder in both children and adults.
PLAN OF THE B O O K This volume is divided into six parts. We hope that all will be of interest to the reader; however, researchers probably will be drawn particularly to the first two parts, and practitioners to the latter four. T h e parts are as follows: • Part I. Prevalence, Consequences, and Etiology of Obesity. The opening chapter by Field and colleagues chronicles the growth of the nation's obesity epidemic and the very significant health and economic burden that it imposes. T h e three chapters that follow describe basic mechanisms of body weight regulation and the remarkable advances in this field in the past decade. A s C h u a and Liebel reveal in Chapter 2, our understanding of the neural and hormonal factors that regulate appetite has progressed well beyond leptin. Tataranni and Ravussin provide a more general overview in Chapter 3 of the regulation of energy intake and expenditure, as well as of body composition. Price, in Chapter 4, discusses advances in the genetics of obesity; he makes it clear that most cases of h u m a n obesity are likely to involve the interaction of multiple genes, which have yet to be identified. Only a handful of obese individuals, for example, suffer from a defect in the ob/ob gene. In Chapter 5, Horgen and Brownell argue convincingly that the obesity epidemic is the product of a "toxic environment" that explicitly encourages the consumption of super-sized portions, while implicitly discouraging physical activity. Stunkard concludes this part in Chapter 6 by discussing t w o
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groups who appear to be most adversely affected by this environment: those who suffer from binge-eating disorder, and those with the newly defined night-eating syndrome. • Part II. Health Consequences of Weight Reduction. Before the assessment and treatment of obesity are considered, the two chapters in this part evaluate the health consequences of weight loss. This is an important issue, given recent concerns that weight loss, as well as cycles of weight loss and regain, m a y be associated with an increased risk of health complications. Gregg and Williamson, however, conclude in Chapter 7 that intentional weight loss (as contrasted to unintentional loss) appears to be associated with decreased risks of morbidity and mortality. W a d d e n and colleagues similarly conclude in Chapter 8 that weight reduction is associated with improvements in m o o d and quality of life, and that dieting (i.e., caloric restriction) in obese adults is not associated with the development of eating disorders. Thus obese adults should not be dissuaded from attempting to lose weight because of fears about adverse health consequences. • Part III. Assessment of the Obese Adult. Obesity is easily diagnosed, usually by sight alone. In Chapter 9, however, Atkinson provides a thorough description of the history and physical examination that should be conducted on overweight or obese individuals. This assessment is critical for identifying health complications of obesity, and thus the medical need for weight reduction. W a d d e n and Phelan discuss the behavioral evaluation of the obese individual in Chapter 10; this includes assessing eating and activity habits, psychosocial status, and readiness for weight loss. This assessment is aided by the patient's completion of a questionnaire that is included as an appendix to the chapter. • Part IV. Treatment of Adult Obesity. A n expert panel convened in 1998 by the N a tional Heart, Lung, and Blood Institute completed an exhaustive review of the safety and efficacy of treatments for obesity. The contributions in this part of the book build upon this foundation. W a d d e n and Osei present an algorithm in Chapter 11 that will assist health care providers in selecting an appropriate therapy, based on the patient's body mass index (BMI) and risk of health complications. A s a rule, patients with a B M I < 30 kg/m^ are most appropriately treated by a program of diet, exercise, and behavior modification. In Chapter 12, Melanson and D w y e r discuss the characteristics of a well-balanced reducing diet, in addition to identifying the potential liabilities of several "best-selling" approaches. Exercise is a critical component of long-term weight control, as reiterated by Blair and Leermakers in Chapter 13. These authors, however, highlight n e w findings that exercise is important for improving cardiovascular health, independently of its effects on body weight, and that health benefits can be obtained with relatively modest levels of physical activity. In Chapter 14, on behavioral weight control. W i n g reviews the efficacy of a comprehensive program that combines diet, exercise, and behavior modification. She also describes efforts over the past decade to improve both the induction and maintenance of weight loss; promising methods include the use of social support and the long-term provision of meal replacement products. Padents with a B M I > 30 kg/m^ are usually at greater risk of weight-related health complications and often have failed to reduce their weight with the interventions previously described. These individuals are candidates for pharmacological therapy, as described in Chapter 15 by Bray, w h o thoroughly reviews the medications that are currently available and those that m a y c o m e to market in future years. Patients with a B M I > 4 0 kg/m^ w h o do not achieve a satisfactory outcome with behavioral or pharmacological approaches are eligible for bariatric surgery, which is described by Latifi and colleagues in Chapter 16. Surgical intervention is clearly associated with greater iatrogenic risks than the aforementioned therapies but is also associated with the best long-term results. T h e central challenge for all obesity therapies, that of maintaining weight loss, is discussed by Perri and Corsica in Chapter 17.
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• Part V. Treatment of Adult Obesity: Additional Approaches and Resources. The interventions described in Part IV have been extensively evaluated, and their safety and efficacy have been described. Overweight and obese individuals, however, are treated by a variety of other approaches. In some cases, they do not have access to the aforementioned therapies; in other cases, patients m a y seek therapies that address psychosocial issues, in addition to their weight. Part V thus highlights other treatments available. Primary care physicians can play an important role in the management of obesity, either by providing treatment directly or by referring patients to an appropriate program. In Chapter 18, Aronne describes the barriers that physicians frequently encounter in treating obesity, and provides suggestions for overcoming them. For practitioners unable to provide diet and exercise counseling in the office, referral to a self-help or commercial program m a y be considered. W o m b l e and colleagues review criteria proposed by the Federal Trade C o m mission for evaluating commercial programs, and describe the treatment components of several popular approaches, in Chapter 19. The five chapters that follow examine methods of adapting treatment to patients' individual needs, as well as addressing concerns beyond weight reduction. In Chapter 20, K u manyika reviews findings that African Americans lose significantly less weight than whites w h e n treated by a behavioral intervention. She explores cultural factors that m a y influence outcome, and proposes innovative ways to improve treatment in minority group members. Complaints of body image dissatisfaction are pervasive a m o n g overweight and obese individuals and are a n e w focus of behavioral treatment, as described by Sarwer and T h o m p s o n in Chapter 21. Cooper and Fairburn argue even more strongly in Chapter 2 2 that the failure to achieve their desired body image is what causes patients to regain lost weight. These authors propose adding a more intensive cognitive component to behavioral weight control therapy, to address body image dissatisfaction and unrealistic weight loss expectations. In Chapter 23, Johnson discusses the importance of improving not only body image but feelings of self-worth. She provides physicians with practical suggestions for improving their care of overweight patients, and encourages obese individuals to confront the weightrelated prejudice and discrimination that can rob them of self-esteem. Efforts to improve body image and self-esteem in obese individuals have frequently been combined with programs that discourage participants from dieting (i.e., restricting calorie intake), in favor of eating in response to the body's natural hunger and satiety cues. In Chapter 24, Foster and M c G u c k i n review the effects of these nondieting approaches on body weight, psychological functioning, and physical health. • Part VI. Childhood Obesity and Obesity Prevention. This volume focuses principally on the treatment of adult obesity. This is consistent with the exceptionally high prevalence of overweight and obesity in U.S. m e n and w o m e n . Although researchers and practitioners must continue to search for more effective treatments for adult obesity, such efforts alone will not be adequate to halt and ultimately reverse the epidemic of obesity. M o r e effective methods are needed to manage obesity in children and adolescents, in order to spare them the health complications that will beset them in adulthood. O f even more pressing concern, however, is the need to prevent the development of obesity in both children and adults. These issues are the topics of the volume's final three chapters. The prevention and treatment of obesity in children require the identification of risk factors for this condition, which are reviewed by Berkowitz and Stunkard in Chapter 25. O n e of the review's principal conclusions is that children w h o become obese do not have low resting energy requirements, contrary to a recent hypothesis. In Chapter 26, Goldfield and colleagues describe behavioral interventions for obese children. The finding that children remain significantly less overweight fully 10 years after receiving treatment stands in sharp contrast to the results of treatment with adults and makes a strong argument for ear-
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Preface
ly intervention. Schmitz and Jeffery, in Chapter 27, tackle the challenge of preventing obesity; they review the results of school, workplace, and community interventions. Although some promising findings are reported, the chapter makes clear that efforts in this area must be increased m a n y times over if w e are to reverse the epidemic of obesity.
ACKNOWLEDGMENTS We are grateful to have received contributions from an outstanding group of investigators, w h o are the world's experts in their areas of study. W e are fortunate to count m a n y of them a m o n g our closest friends and colleagues. All have our deepest thanks and appreciation. Jim Nageotte, senior editor at T h e Guilford Press, provided invaluable counsel on all aspects of the book, from framing the big picture to addressing the smallest details. W e thank him, as w e do Laura Specht Patchkofsky and Marie Sprayberry (whose editorial expertise and superb copy editing, respectively, contributed to the uniformly high quality of all the chapters). W e also thank Seymour Weingarten, editor-in-chief at T h e Guilford Press, for making this work possible. This book would not have been completed without the superb editorial assistance of Shirley W a n g , our unit's former research coordinator, w h o is n o w pursing her doctorate in clinical psychology. She, with the able assistance of Rebecca Rothman, read multiple drafts of chapters, tracked d o w n missing references and figures, and maintained exceptionally good h u m o r throughout the production of the book. W e also thank Jane Seagrave and John Kennedy for their generous assistance with these efforts. O u r research on obesity has been supported for m a n y years by the National Institutes of Health, to which w e are grateful. Preparation of the individual chapters that w e contributed w a s supported in part by Grant Nos. D K - 5 6 1 1 4 and D K - 5 6 1 2 4 (to T h o m a s A. W a d d e n ) and by Grant Nos. DK-56735 and M H - 5 6 2 5 1 (to Albert J. Stunkard). A n d finally, w e thank our wives for their love, support, and understanding. They ultimately have contributed to this volume, as they do to all significant events in our lives.
Thomas A. Wadden Albert J. Stunkard
C o n t e n t s
PART I. PREVALENCE, CONSEQUENCES, A N D ETIOLOGY OF OBESITY 1. Epidemiology and Health and Economic Consequences of Obesity 3 Alison E. Field, Joaquin Barnoya, and Graham A. Colditz 2. Body Weight Regulation: Neural, Endocrine, and Autocrine Mechanisms 19 Streamson C. Chua, Jr., and Rudolph L. Leibel 3. Energy Metabohsm and Obesity 42 P. A. Tataranni and Eric Ravussin 4. Genetics and Common Obesities: Background, Current Status, Strategies, 73 and Future Prospects R. Arlen Price 5. Confronting the Toxic Environment: Environmental Public Health Actions 95 in a World Crisis Katherine Battle Horgen and Kelly D. Brownell 6. Binge-Eating Disorder and Night-Eating Syndrome 107 Albert J. Stunkard
PART II. HEALTH CONSEQUENCES OF WEIGHT REDUCTION
7. The Relationship of Intentional Weight Loss to Disease Incidence and Mortality 125 Edward W . Gregg and David F. Williamson 8. Psychosocial Consequences of Obesity and Weight Loss 144 Thomas A. Wadden, Leslie G. Womble, Albert J. Stunkard, and Drew A. Anderson
PART III. ASSESSMENT OF THE OBESE ADULT 9. Medical Evaluation of the Obese Padent 173 Richard L. Atkinson xiii
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10. Behavioral Assessment of the Obese Patient 186 Thomas A. Wadden and Suzanne Phelan
PART IV. TREATMENT OF ADULT OBESITY 11. The Treatment of Obesity: An Overview 229 Thomas A. Wadden and Suzette Osei 12. Popular Diets for Treatment of Overweight and Obesity 249 Kathleen Melanson and Johanna Dwyer 13. Exercise and Weight Management 283 Steven N. Blair and Elizabeth A. Leermakers 14. Behavioral Weight Control 301 Rena R. Wing 15. Drug Treatment of Obesity 317 George A. Bray 16. Surgical Treatment of Obesity 339 Rifat Latifi, John M . Kellum, Eric J. D e Maria, and Harvey J. Sugerman 17. Improving the Maintenance of Weight Lost in Behavioral Treatment of Obesity 357 Michael G. Perri and Joyce A. Corsica
PARTV. TREATMENT OF ADULT OBESITY: ADDITIONAL A P P R O A C H E S A N D R E S O U R C E S 18. Treatment of Obesity in the Primary Care Setting 383 Louis J. Aronne 19. Commercial and Self-Help Weight Loss Programs 395 Leslie G. Womble, Shirley S. Wang, and Thomas A. Wadden 20. Obesity Treatment in Minorities 416 Shiriki K. Kumanyika 21. Obesity and Body Image Disturbance 447 David B. Sarwer and J. Kevin Thompson 11. Cognitive-Behavioral Treatment of Obesity 465 Zafra Cooper and Christopher G. Fairburn 23. Obesity, Weight Management, and Self-Esteem 480 Carol Johnson 24. Nondieting Approaches: Principles, Practices, and Evidence 494 Gary D. Foster and Brian G. McGuckin
Contents PART VI. CHILDHOOD OBESITY AND OBESITY PREVENTION 25. Development of Childhood Obesity 515 Robert I. Berkowitz and Albert J. Stunkard 26. Treatment of Pediatric Obesity 532 Gary S. Goldfield, Hollie A. Raynor, and Leonard H. Epstein 17. Prevention of Obesity 556 Kathryn H. Schmitz and Robert W . Jeffery Author Index 595 Subject Index 617
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PARTI
PREVALENCE, CONSEQUENCES, A N D
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A L I S O N E. FIELD JOAQUIN BARNOYA G R A H A M A. C O L D I T Z
Obesity is a serious public health problem in the United States. The prevalence of obesity has increased sharply a m o n g children and adults over the past three decades. According to the third National Health and Nutrition Examination Survey ( N H A N E S III), 3 2 % of adults in the United States are overweight, and an additional 2 2 . 5 % are obese (Flegal, CaroU, Kuczmarski, & Johnson, 1998). The prevalences are m u c h higher a m o n g African Americans and Hispanics. Approximately 6 7 % of adult African American and Hispanic w o m e n are overweight or obese, compared with 4 6 % of non-Hispanic white w o m e n . Obesity is also a public health problem in other developed and affluent countries and is n o w spreading to less affluent countries, such as Mexico, BrazU, and Cuba (Popkin, 1994). Although the terms "overweight" and "obesity" are used almost interchangeably in the scientific and lay literature, the two concepts are not identical. "Overweight" refers to weighing more than a standard level for height and age; "obesity" refers to excessive body fat. Overweight individuals m a y have excessive stores of body fat; however, highly active people w h o have substantial muscle mass m a y weigh slightly more than the standard for their height despite low body fat. Thus people m a y be overweight but not over-fat. Obesity has traditionally been classified based on body fat stores, but n o w is frequently defined as weighing substantially more than a standard level for age and height. The assumption has been that individuals w h o weigh m u c h more than the standard for their height are very likely to have excessive body fat stores. This approach to categorizing people works quite well, since it is rare for an athlete to have sufficient muscle mass to be misclassified as obese. In clinical practice, it is obvious that a highly fit individual does not have excessive body fat; thus misclassification is only a potential problem in nonclinical settings. Obesity and higher relative weights in adults are risk factors for cardiovascular disease ( C V D ) (Manson et al., 1990; Rexrode et al., 1997), certain cancers (Huang et al., 1997; Shoff &c N e w c o m b , 1998; Tornberg & Carstensen, 1994), diabetes (Colditz et al., 1990),
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PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY OF OBESITY
and mortality (Manson et al, 1995; Willett, Dietz, & Colditz, 1999). Excessive weight a exacerbates many other chronic diseases, such as hypertension (Witteman et al., 1990), osteoarthritis (Carman, Sowers, Hawthorne, & Weissfeld, 1994; Davis, Ettinger, Neuhaus, & Hauck, 1988), gallstones (Maclure et al., 1989), dyslipidemia, and musculoskeletal problems (Beirman & Hirsch, 1981; Mann, 1974; VanltaUie, 1979). In addition to the physical health problems related to obesity, there are numerous psychological and psychosocial effects (Fine et al., 1999). Because psychological and psychosocial factors ultimately influence health and general well-being, the social impact of obesity is far-reaching.
DEFINITIONS, PREVALENCE, A N D AGE-RELATED C H A N G E S Definitions of Overweight and Obesity Body mass index (BMI), a formula that combines weight and height, is commonly used in epidemiological studies assessing the relationship between weight and disease. In addition, the public health recommendations on body weight are based on BMI, which is computed as weight (in kilograms) divided by height (in meters) squared. The advantage of using B M I instead of weight in pounds or kilograms is that it accounts for height—an essential piece of information when one is evaluating weight. For example, a w o m a n who weighs 145 pounds is overweight if she is 5 feet 4 inches tall, but a healthy weight if she is 5 feet 8 inches tall. The World Health Organization (1998) and the National Heart, Lung, and Blood Institue (NHLBI, 1998) have classified B M I as follows: <18.5 kg/m^ is underweight; 18.5-24.9 kg/m^ is the healthy weight range; 25-29.9 kg/m^ is overweight; and £ 3 0 kg/m^ is obese. As can be seen in Figure 1.1, a woman, who at 5 feet 4 inches and 145 pounds is considered overweight would be considered obese if she weighed 180 pounds.
Prevalence of Overweight and Obesity Currently, approximately 60 million U.S. adults are overweight (Flegal et al., 1998; al Center for Health Statistics, 1996), and the prevalence of both overweight and obesity has been increasing (Kuczmarski, Flegal, Campbell, & Johnson, 1994). The age-adjusted prevalence of obesity increased by 8 % from 1980 to 1994 (Flegal et al., 1998). More than 5 0 % of U.S. adults over 20 years old exceed the healthy weight ranges (i.e., B M I > 25 kg/m^): 59.3% of men and 49.6% of women, or 54.4% of the total U.S. population. In addition, 24.9% of w o m e n andl9.9% of men, or overall 25.4% of adults, are obese (BMI > 30 kg/m2).
Body Weight and Age
Body weight and body composition are a function of genetics, health status, basal met ic factors, dietary intake, physical activity, race, and hormonal factors. The onset (i.e., childhood, adolescence, or adulthood) and duration of obesity, as well as weight change, may have an important impact on health. Changes over time in basal metabolic factors, hormones, dietary intake, and physical activity result in changes in body weight and composition. Although B M I does an adequate job of classifying young- and middle-aged people in terms of body weight, it is less accurate among elderly individuals. Old age is frequently accompanied by a decline in lean body mass and changes in the distribution of body fat. Therefore, when body weight and risk of disease are being assessed among elderly persons, both B M I and waist circumference should be used.
Epidemiology and LHealth and Economic Consequences
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23
D (18.5-24.9) = NORAML WEIGHT n (25-29.9) = OVERWEIGHT n (>30) = OBESE n (si8.5) = UNDERWEIGHT F I G U R E 1.1. B M I chart.
C O N S E Q U E N C E S O F OVERWEIGHT Mortality Excessive weight increases the risk of death, particularly death due to C V D . Although there has been debate about whether the relationship between weight and risk of death is linear or J-shaped, the resuks have consistently s h o w n that aduhs with B M I over 3 0 kg/m^ are at increased risk of death (Manson et al., 1995; Stevens et al., 1998). A m o n g 45- to 75-yearold m e n and w o m e n in the American Cancer Society's Cancer Prevention Study I, the risk of death increased linearly with B M I a m o n g those w h o had never smoked. T h e risk w a s particularly pronounced for death from C V D and a m o n g m e n (Stevens et al, 1998). A m o n g 115,195 w o m e n in the Nurses' Health Study, M a n s o n and colleagues (1995) observed that the risk of death over 16 years of follow-up rose steadily with B M I (see Figure 1.2). Although there w a s evidence of a J-shaped curve in the age-adjusted analysis, there w a s n o evidence of an increased risk of death a m o n g the leanest w o m e n in the group w h o had never smoked. Although mortality is a clearly defined outcome, the results of mortality analyses can
W o m e n Wtio Never S m o k e d (1499 deattis)
All W o m e n (4726 deattis) 2.5
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1.5
cr •o 1.0 0) •55 0.5 TO < 0.0
a. •o 1.0 0) tn 0.5 T3 < 0.0
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Chi for trend = 9.02 P<0.001
.Ol n>'
Cb (% Qi .'v'"' ,^' ,'d''
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•v^Body-Mass Index
Body-Mass Index
Current Smokers (1724 deaths)
Former Smokers (1503 deaths)
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^ S ^ I l l ^ Chi for trend = 5.20 P<0.001
0.0
.!£ C0) C <1) > •^ OJ oc -n m U 3) t) <
2.0 1.5 1.0 ns
0.0
Chi for trend = 2.87 P = 0.004
j^ A
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Body-Mass Index
Body-Mass Index
F I G U R E 1.2. Relative risk of death from all causes, 1976 through 1992, according to body mass index, for all w o m e n , w o m e n w h o never smoked, former smokers, and current smokers. All relative risks have been adjusted for age in 5-year categories. For the total cohort and for current smokers, relative risks have been additionally adjusted for the intensity of smoking (1 to 14, 15 to 24, or > 2 5 cigarettes per day). T h e bars represent 9 5 % confidence intervals. In all cases, the reference category is the w o m e n with a body mass index below 19.0. F r o m M a n s o n et al. (1995). Copyright 1995 by Massachusetts Medical Society. Reprinted by permission.
Epidemiology and Health and Economic Consequences
7
be difficult to interpret. Except for diseases that are almost always fatal regardless ment, mortality is a function of incidence of disease, stage of illness at diagnosis, and the effectiveness of treatment. M a n y forms of C V D are treatable by either pharmacotherapy or intervention (i.e., angioplasty or surgery). Thus the relationship between excess weight and death from C V D does not necessarily translate to the same relationship with the development of C V D .
Morbidity Cardiovascular Disease
CVD is the leading cause of death in the United States, accounting for 45.2% of all de Approximately 58 million persons in the United States have one or more types of C V D ("Missed Opportunities in Preventive Counseling," 1998), including coronary heart disease (CHD), stroke, and hypertension. Heart Disease. Young and middle-aged men and women who are overweight or obese are more hkely than their leaner peers to develop heart disease (see Figure 1.3). R i m m and colleagues (1995) followed 29,122 U.S. men w h o were 40 to 75 years of age. They observed that among the men under 65 years of age, the risk of developing C H D increased with increasing category of BMI. M e n w h o were overweight were almost twice as likely as those with a B M I below 23 kg/m^ to develop C H D (relative risk [RR] = 1.7, 9 5 % confidence interval [CI] = 1.1-2.7), whereas men with a B M I of at least 33 kg/m^ were three times more likely to develop C H D (RR = 3.4, 9 5 % CI = 1.7-7.1) during the 3 years of follow-up. C H D is less c o m m o n among w o m e n than men, particularly before menopause. Nevertheless, associations between excessive weight and C H D have been observed in adult women. Harris, Ballard-Barbasch, Madans, Makue, and Feldman (1993) observed that
Women
^
• • X A
Type 2 diabetes Cholelithiasis Hypertension Coronary heart disease
Men 6-1 5 4
• • X A
Type 2 diabetes Cholelithiasis Hypertension Coronary heart disease
3-1 0) CC
2
T—I—I—1—I— 24 25 — I — 27 28 — I — 30 29 26 21 22 23 Body-Mass Index
—I—I—I—1—I— -I—I—I—I— — I — 29 30 =S21 22 23 24 25 26 27 28 Body-Mass Index
F I G U R E 1.3. Relation between body mass index up to 30 and the relative risk of Type 2 diabetes, hypertension, coronary heart disease, and cholelithiasis. Panel A shows these relations for w o m e n in the Nurses' Health Study, initially 3 0 to 55 years of age, w h o were followed for u p to 18 years. Panel B shows the same relations for m e n in the Health Professionals F o U o w - U p Study, initially 4 0 to 65 years of age, w h o were followed for u p to 10 years. F r o m Willett, Dietz, and Colditz (1999). Copyright 1999 by Massachusetts Medical Society. Reprinted by permission.
8
PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY OF OBESITY
among 1,259 white women in NHANES I, those who were overweight (BMI > 29 kg/m-^) and had fairly stable weights had a threefold increased risk (RR = 2.7, 9 5 % CI = 1.7-4.4) of developing C H D . In addition, independent of overall adiposity (as measured by BMI), w o m e n with a large waist circumference (38 inches) or waist-to-hip ratio ( W H R > 0.88) were approximately three times more likely than their peers to develop C H D over an 8-year period (Rexrode et al., 1998). Overweight w o m e n are also at increased risk of ischemic stroke. Among 116,759 w o m e n aged 30 to 55 years in the Nurses' Health Study, women with B M I over 29 kg/m^ were approximately twice as likely as w o m e n with B M I under 21 kg/m^ to have an ischemic stroke during 16 years of follow-up (Rexrode et al., 1997). Not only are obese adults more likely to develop C H D , but they are also more likely to die from it. During 12 years of follow-up of 48,287 Dutch men and w o m e n aged 30 to 54 , Seidell, Verschuren, van Leer, and Kromhout (1996) observed that men and w o m e n who were obese (i.e., B M I > 30 kg/m^) were three times more hkely than their nonoverweight peers (BMI < 25 kg/m^) to die from C H D . Moreover, the authors estimated that 2 0 % - 3 0 % of the C H D mortality could be attributed to being overweight. Excessive weight earlier in life is also predictive of C H D mortality. Must, Jacques, Dallal, Bajema, and Dietz (1992) followed 508 adolescents w h o participated in the Harvard Growth Study of 1922 to 1935. The adolescents who were overweight were twice as likely as their lean peers to die from C H D during adulthood (RR = 2.3, 9 5 % CI = 1.4-4.1). There are several mechanisms through which obesity and weight gain might increase the risk of C H D . Hyperlipidemia is one mechanism. B M I is correlated with triglyceride levels, as well as high-density lipoprotein (HDL) levels. L o w H D L levels are more predictive than high total cholesterol of developing heart disease. Thus obesity increases risk of heart disease in part by increasing total triglycerides and making the ratio of H D L to low-density lipoprotein (LDL) less favorable (Bray, 1996). Hypertension. Approximately 25% of adult Americans have high blood pressure. From 1986 to 1996, the death rate from high blood pressure increased 6.8% (American Heart Association, 2000). Although high blood pressure (i.e., hypertension) is a highly treatable condition, if left untreated its consequences are severe. Hypertension is a strong predictor of more severe C V D . The combination of obesity and hypertension is associated with an increased risk of cardiac failure due to thickening of the ventricular wall and increased heart volume (Alpert & Hashimi, 1993). Both weight (Ascherio et al, 1992; Folsom, Prineas, Kaye, & Soler, 1989; Witteman et al, 1989) and weight gain (Field et al., 1999; Yong, Kuller, Rutan, & Bunker, 1993) are positively associated with the development of hypertension. A m o n g both men and women, there is a linear relation between body weight and blood pressure. Witteman and colleagues (1989) observed that women with a B M I between 26 and 28 kg/m^ were approximately threetimesmore likely then women with a B M I under 23 kg/m^ (RR = 2.8) to develop hypertension over a 4-year period, and women with a B M I of 32 kg/m^ or more were almost six times more likely to develop hypertension. Blood pressure is very sensitive to weight change. A maintained weight loss of 1 0 % - 1 5 % can resuh in a sustained lowering of blood pressure, as well as improving other C H D risk factors (Wing & Jeffrey, 1995). Thus weight loss is recommended to patients with mildly elevated blood pressure or risk factors for developing C V D . Huang and colleagues (1998) observed that among 82,473 w o m e n in the Nurses' Health Study, those who lost at least 10 kg and were able to maintain the loss for at least 2 years were 4 5 % less hkely to develop hypertension (RR = 0.6, 9 5 % CI = 0.4-0.7) than their peers w h o were weightstable. By contrast, w o m e n who gained 10-19.9 kg were twice as likely (RR = 2.2, 9 5 % CI = 2.0-2.4) to develop hypertension. There are several mechanisms through which obesity
Epidemiology and Health and Economic Consequences
9
causes hypertension. Hyperinsulinemia, which is common among overweight and obese individuals, can cause activation of the sympathetic nervous system as well as sodium retention, both of which increase the risk of developing hypertension (Mikhail, Golub, & Tuck, 1999).
Diabetes The incidence of Type 2 diabetes mellitus has risen steadily over the past 30 years. Diabetes is a prevalent and serious disease, affecting approximately 14 million people in the United States (National Institute of Diabetes and Digestive and Kidney Diseases [ N I D D K ] , 2000b). People with diabetes are at substantially elevated risk for blindness, kidney disease, heart disease, stroke, and death. Diabetes is the seventh leading cause of death in the United States ( N I D D K , 2000b) Type 2 diabetes is characterized by peripheral insulin resistance, impaired regulation of hepatic glucose production, and low p-cell function. Excessive weight increases the risk of Type 2 diabetes through insulin resistance (Mahler &c Adler, 1999). Not only are overweight m e n and w o m e n at substantially increased risk for developing Type 2 diabetes (Chan, R i m m , Colditz, Stampfer, & Willett, 1994; Lundgren, Bengtsson, Blohme, Lapidus, & Sjostrom, 1988), but adults at the upper end of the "healthy weight range" (i.e., B M I of 20-24.9 kg/m^) are also at risk because of the strong linear relation between B M I and risk. In addition, even after adjustment for weight, weight gain has been observed to be strongly associated with the risk of developing diabetes (Colditz, Willett, Rotnitsky, & Manson, 1995; Holbrook, Barrett-Connor, & Wingard, 1989). Colditz and colleagues (1995) observed that a m o n g 114,281 female nurses 30 to 55 years of age, even a modest weight gain (5-7.9 kg) since age 18 was associated with a 9 0 % increase in risk of diabetes (RR = 1.9; 9 5 % CI = 1.5-2.3). Moreover, similar results were observed in a parallel study a m o n g m e n (Chan et al., 1994). Independent of weight, location of adiposity has an important role in the development of Type 2 diabetes. Carey and colleagues (1997) observed that w o m e n with a large waist circumference (36.2 inches) were more than five times as likely as their peers with small waists (26.2 inches) to develop Type 2 diabetes, regardless of their overall adiposity (measured by B M I ) . Moreover, a m o n g 15,432 w o m e n , Hartz, Rupley, Kalkhoff, and R i m m (1983) found that the prevalence of diabetes within each weight stratum (nonobese, moderately obese, and severely obese) increased with W H R . A m o n g the nonobese w o m e n , the risk increased in a gradual linear fashion. A m o n g the severely obese w o m e n , the risk increased sharply from approximately 6 % for those with a W H R under 0.72 to 1 6 . 5 % among w o m e n with a W H R over 0.81. Similar associations have been seen in men. Ohlson and colleagues (1985) observed that B M I and W H R were significant independent predictors of developing diabetes over a 13.5-year follow-up of 792 Swedish men. Approximately 1 5 % of the m e n in the highest tertile of both W H R and B M I developed diabetes, compared with only 0 . 5 % of the m e n in the lowest tertile of both factors.
Cancers Excessive weight is associated with the development of numerous types of cancer, including breast (among postmenopausal w o m e n ) , endometrial, gastric, and colon. The racial differences in the prevalence of excessive weight m a y partially explain the elevated rate of certain cancers a m o n g African Americans. Obesity is thought to increase risk of developing cancer primarily through its effect on hormones. However, certain cancers (e.g., renal cell carcinom a ) are related to obesity through other, not well-understood mechanisms.
10
PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY O F OBESITY
Among premenopausal women, those who are overweight are less likely to develop breast cancer (Peacock, White, Daling, Voigt, & Malone, 1999). The decrease in risk m a y be due to a higher prevalence of menstrual irregularities and their associated low estrogen levels in overweight w o m e n . The relation is quite different in postmenopausal w o m e n , a m o n g w h o m obesity is associated with an increased risk of developing breast cancer. Adipose tissue is the primary source of estrogen a m o n g postmenopausal w o m e n w h o do not use hormone replacement therapy. Therefore, it is not surprising that the obesity-related increase in risk is restricted to w o m e n w h o do not use hormone replacement therapy (Huang et al., 1997). Breast cancer is more c o m m o n a m o n g post- than premenopausal w o m e n ; therefore, it is it fair to say that obesity promotes more breast cancers than it prevents. In addition, a m o n g w o m e n diagnosed with breast cancer, obesity is associated with a higher mortality rate (Kyogoku et al., 1990). Overweight w o m e n are more likely than their leaner peers to develop endometrial cancer (Shoff & N e w c o m b , 1998), which is the most c o m m o n gynecological cancer in the United States and the fourth most c o m m o n cancer overall in w o m e n . The increase in risk is strongest in older w o m e n (Tornberg &c Carstensen, 1994). Although the data are quite limited, the results from primarily case-control studies suggest that the risk of ovarian cancer increases with relative weight (Farrow, Weiss, Lyon, & Daling, 1989). In addition to increasing the risk of developing hormone-related cancers, obesity is associated with the development of other types of cancer, such as esophageal, stomach, and colon cancer. Obesity has a k n o w n relationship with gastroesophageal reflux, a risk factor for esophogeal adenocarcinoma (Vaughn, Davis, Fristal, & Thomas, 1995). Obese adults are up to 16 times as likely as lean adults to develop this type of cancer (Lagergren, Bergstrom, & Nyren, 1999). The increasing prevalence of obesity, coupled with the strength of the association between obesity and adenocarcinoma of the gastric cardia, m a y explain w h y the incidence of the tumor has been increasing dramatically in the recent past (Vaughn et al., 1995). Colon cancer is the third most c o m m o n cancer in the United States. A m o n g the 13,420 m e n and w o m e n in the N H A N E S I follow-up study, the risk of colon cancer associated with excess weight was similar in m e n and w o m e n (Ford, 1999). Although other researchers have observed an increase in risk associated with weight only among m e n (Giovannucci et al, 1995; Le Marchang, WUkens, Kolonel, Hankin, & Lyu, 1997), the more recent data show an elevated risk in w o m e n (Martinez et al., 1997). Gallstones Gallstones are a fairly common, often quite painful condition and are most common among overweight adults. Gallstones are believed to form w h e n the bile contains too m u c h cholesterol or bilirubin or not enough bile salts, or w h e n the gallbladder does not empty properly. Stones can range in size, and m a n y of them are asymptomatic; however, if the stones lodge in any of the ducts that carry bile from the liver, problems can arise. The trapped bile in the ducts can lead to inflammation in the gallbladder, the ducts themselves, or the liver. If prolonged, the blockages can have severe consequences affecting the gallbladder, liver, or pancreas. Gallstones that are symptomatic can be very painful. The most c o m m o n course of treatment is laparoscopic surgery to remove the gallbladder (i.e., laparoscopic cholecystectomy). Although gallstones do form in lean aduhs, the relationship a m o n g weight, weight change, and gallstone formation is very strong. Moreover, w o m e n are more hkely than m e n to develop gallstones. A m o n g 16,884 adults in N H A N E S III, the prevalence of gallbladder disease significantly increased with weight status (Must et al., 1999). The relationship was stronger a m o n g w o m e n than men, and stronger in those less than 55 years of age. C o m -
Epidemiology and FHealth and Economic Consequences
11
pared with women in the healthy weight range, overweight women were twice as likely to report gallbladder disease (odds ratio [OR] = 1.9, 9 5 % CI = 1.3-3.0), and w o m e n with a B M I of 40 kg/m^ or over were more than five times as likely to report the diagnosis ( O R = 5.2, 9 5 % CI = 2.9-8.8). The association between body weight and gallbladder disease also has been observed prospectively. Over an 8-year period, 2,122 cases of symptomatic gallstones were diagnosed a m o n g the 90,302 w o m e n in the Nurses' Health Study (Stampfer, Maclure, Colditz, M a n s o n , & Willett, 1992). The risk of developing symptomatic gallstones (that were not removed) and the risk of having a cholecystectomy increased linearly with B M I . W o m e n with a B M I between 25 and 26 kg/m^ were approximately 6 0 % more likely than w o m e n with a B M I under 24 kg/m^ to have a cholecystectomy or develop symptomatic gallstones (RR = 1.6, 9 5 % CI = 1.4-1.9), whereas w o m e n with a B M I of 30-34.9 kg/m^ were more than three times as likely to develop gallstones (RR = 3.5, 9 5 % CI = 3.1-4.0). The most likely mechanism through which obesity increases the risk of developing gallstones is the reduction in the amount of bile salts in bile, which results in more cholesterol. In addition, obesity is associated with decreased gallbladder emptying ( N I D D K , 2000a).
Osteoarthritis Approximately 16 million people in the United States have osteoarthritis (Arthritis Foundation, 2000), a disease that causes the breakdown of cartilage in joints. The hips, knees, and spine are the most c o m m o n sites of osteoarthritis. A s a result of the degeneration of the cartilage, bones that were previously cushioned by cartilage rub together and cause considerable pain. Although the condition has not been as well studied as other chronic diseases, such as C H D and cancer, it does appear that overweight adults are more than twice as likely as their leaner peers to develop osteoarthritis in the hip (Cooper et al., 1998). In addition, excessive weight is associated with the development and course of osteoarthritis of the knee (Cicuttini, Baker, & Spector, 1996; Hart & Spector, 1993; Manninen, Riihimaki, Hehovaara, & Makela, 1996). Excessive weight causes additional strain on the joints and can lead to their degradation.
Benign Prostatic IHyperplasia Prostate enlargement is common among men. Benign prostatic hyperplasia (BPH) rarely causes symptoms a m o n g young men; however, more than 5 0 % of m e n in their 60s and an estimated 9 0 % in their 70s and 80s have some symptoms of B P H (Patient Information Resource, 2000). Surgical treatment (i.e., prostatectomy) is very c o m m o n . A n estimated 350,000 operations are preformed annually in the United States (Patient Information Resource, 2000). A m o n g 25,892 m e n in the Health Professionals' FoUow-Up Study, independent of age, smoking, and B M I , m e n with a large waist circumference (>43 inches vs. <35 inches) were more than twice as likely ( O R = 2.4, 9 5 % CI = 1.4-4.0) to develop B P H and have a prostatectomy (Giovannucci et al., 1994). Centrally located adiposity m a y increase the risk of developing B P H by increasing the estrogen-to-androgen ratio and sympathetic nervous activity.
Mental Health and Lifestyle Outcomes Despite the rapid increase in the prevalence of overweight, there are considerable social consequences of being overweight in a Westernized society that values thinness and fitness. Obese w o m e n are less likely to be hired, more likely to have their performance rated nega-
12
PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY OF OBESITY
tively, and less likely to be promoted (Larkin & Pines, 1979; Roe & Eichwort, 1976). Moreover, among both normal and overweight women, weight gain is associated with poorer well-being (Rumpel, Ingram, Harris, & Madans, 1994). A m o n g approximately 1,000 adults in a weight gain prevention program, 2 2 % of the w o m e n and 1 7 % of the men reported that they had been mistreated because of their weight (Falkner et al., 1999). The prevalence increased across quartiles of BMI, from 5.7% among the leanest quartile to 42.5% among the heaviest participants. Gortmaker, Must, Perrin, Sobol, and Dietz (1993) followed a sample of 16- to 24-year-old people over 8 years. They observed that women w h o were overweight were approximately 2 0 % and overweight men 1 1 % less likely to marry. In addition to the adverse social consequences, overweight individuals are less likely than their leaner peers to be promoted at work (Wadden & Stunkard, 1985). Sonne-Holm and Sorensen (1986) observed that among 3,267 men in Copenhagen at each level of education attainment, the attained level of social class was significantly lower for obese men. Obesity has an impact on many aspects of quality of hfe. The association between quality of life and body weight has been assessed among w o m e n in the Nurses' Health Study. In both cross-sectional (Coakley et al., 1998) and prospective (Fine et al., 1999) analyses using the Medical Outcome Study 36-Item Short-Form Health Survey to measure health-related quality of life, there was a linear association between increasing B M I and decreases in physical functioning and vitality. Moreover, weight change over a 4-year period was associated with changes in quality of life. W o m e n w h o gained more than 20 pounds over the 4 years had significant decreases in physical functioning, whereas weight losses were associated with increases in functioning and vitality.
E C O N O M I C C O S T S O F OBESITY
Disease burden is commonly measured by mortality; however, it is an inadequate measur because it does not account for the morbidity associated with chronic conditions, nor does it capture the impact of lifestyle on health-related quality of life. Economic measures, on the other hand, can summarize this broad range of health effects and account for both nonfatal and fatal conditions. Thus they may provide a more comprehensive summary of the public health impact of such conditions as obesity. Economic costs can be compartmentalized into direct and indirect costs. The direct costs of dlness include the costs of diagnosis and treatment related to any disease (hospital stay, nursing home, medications, physician visits). Indirect costs include the value of lost productivity, including wages lost by people unable to work because of disease and wages forgone due to premature mortality. In the United States, the direct cost of obesity has been estimated to be $70 billion, or 7 % of health care expenditures. In other countries, the costs range from 2 % in France (Levy, Levy, Le Pen, & Basdevant, 1995) and Australia (Segal, Carter, &c Zimmet, 1994) to 4 % of the national health care costs in the Netherlands (SeideU, 1995). The indirect costs of early retirement and increased risk of disability pensions are not insignificant. A m o n g adult w o m e n in Sweden, obese subjects were 1.5 to 1.9 times more likely to take sick leave, and 1 2 % of obese women had disability pensions attributable to obesity (Narbro, Jonsson, Larsson, Wedel, & Sjostrom, 1996). Overall, approximately 1 0 % of sick leave and disability pensions for w o m e n may be related to obesity and obesity-related conditions. Colditz (1999) estimated that the indirect costs attributable to obesity in the United States amounted to at least $48 billion in 1995. However, Colditz noted that because there are adverse health effects associated with overweight below a B M I of 30 (NHLBI 1998U.S. Department of Agriculture and U.S. Department of Health and H u m a n Services,
Epidemiology and F^ealth and Economic Consequences
13
1995), his estimate is the lower bound of the health care cost, since substantial additional costs are incurred a m o n g those w h o are overweight (i.e., a B M I of 25-29.9 kg/m^) but not obese. Gorsky, P a m u k , Williamson, Shaffer, and Koplan (1996) simulated three hypothetical cohorts to estimate the costs of health care according to level of obesity over a 25-year period, discounting future costs at 3 % per year. They estimated that an additional $16 bilhon will be spent over the next 25 years in treating adverse health effects of obesity in middleaged w o m e n . Using an incidence-based approach to cost of illness, T h o m p s o n , Edelsberg, Colditz, Bird, and Oster (1999) estimated the excess costs of health services according to level of obesity. Using a conservative approach that did not include any future weight gain, and starting with N H A N E S III population estimates for B M I , cholesterol, hypertension, and diabetes, they estimated the lifetime future costs per person as comparable to those for smoking. The health care costs that have been estimated to date are underestimations of the true costs, since they do not consider the impact of reduced physical functioning (Coakley et al., 1998; Fontaine, Cheskin, & Barofsky, 1996), the increased risk of infertility a m o n g young w o m e n (Rich-Edwards et al., 1994), or the increased risk of asthma, all of which are directly associated with increasing adiposity. The costs associated with infertility and asthma treatment are substantial and should be included in future analyses of the costs of obesity.
CONCLUSION Obesity is a serious public health problem in the United States and other developed countries, and is becoming a problem in developing countries as well. The prevalence of obesity in both children and adults in the United States, as well as in other Westernized countries, is rising rapidly, so that w e can expect the rates of C V D , diabetes, certain cancers, gallbladder disease, and osteoarthritis to rise over the next several decades. Despite the health risks of obesity and the societal pressures to be thin, most adult Americans are steadily gaining weight. With rare exceptions, obesity is a preventable disease. Prevention of the development of obesity needs to be m a d e a public health priority. In addition, doctors should counsel their patients on the importance of maintaining a healthy weight and help their overweight patients lose weight and maintain the loss. Physical activity is important for maintaining weight losses, as well as preventing excessive weight gain. In addition, the deleterious health effects of excessive weight are at least partially alleviated by being fit (Blair & Brodney, 1999). Thus it is essential that children and adults be encouraged to be active, regardless of their weight. The benefits of weight loss are substantial in terms of reducing the risk of diabetes and hypertension. Although m a n y people m a y be unable to lose and maintain a sufficient amount of weight for them to be happy with their weight and shape, even a modest 1 0 % sustained weight loss can have tremendous benefits for their physical health. Although treatments for C V D and cancer have improved, prevention should be the goal. If the development of obesity could be prevented, a substantial proportion of the burden of C V D , cancer, and gallbladder disease could be avoided.
REFERENCES Alpert, M. A., &C Hashimi, M. W. (1993). Obesity and the heart. American Journal of Medical Science, 306, 117-123.
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PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY O F OBESITV
American Heart Association. (2000). High blood pressure. [Online]. Available: http://www.americanheart.org/statistics/06hghbld.html [2000, January 27]. Arthritis Foundation. (2000). Osteoarthritis [Online]. Available: http://wvirw.arthritis.org/offices/ al/about/osteoarthritis.asp [2000, January 27]. Ascherio, A., R i m m , E. B., Giovannucci, E. L., Colditz, G. A., Rosner, B., Willett, W . C , Sacks, F., & Stampfer, M . J. (1992). A prospective study of nutritional factors and hypertension among U S men. Circulation, 86, 1475-1484. Beirman, E. L., &C Hirsch, J. (1981). Obesity. In R. H. Williams (Ed.), Textbook of endocrinology (pp. 906-921). Philadelphia: W.B. Saunders. Blair, S. N., &c Brodney, S. (1999). Effects of physical inactivity and obesity on morbidity and mortality: Current evidence and research issues. Medical Science in Sports and Exercise, 31 (Suppl.), 646-662. Bray, G. A. (1996). Health hazards of obesity. Endocrinology and Metabolism Clinics of North America, 25, 907-919. Carey, V. J., Walters, E. E., Colditz, G. A., Solomon, C. G., Willett, W . C , Rosner, B. A., Speizer, F. E., &C Manson, J. E. (1997). Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women: The Nurses' Health Study. American Journal of Epidemiology, 145, 614-619. Carman, W . J., Sowers, M., Hawthorne, V. M., & Weissfeld, L. A. (1994). Obesity as a risk factor for osteoarthritis of the hand and wrist: A prospective study. American Journal of Epidemiology, 139, 119-129. Chan, J. M., R i m m , E. B., Colditz, G. A., Stampfer, M . J., & Willett, W . C. (1994). Obesity, fat distribution, and weight gain as a risk factor for clinical diabetes in men. Diabetes Care, 17, 961-969. Cicuttini, F. M., Baker, J. R., & Spector, T. D. (1996). The association of obesity with osteoarthritis of the hand and knee in women: A twin study. Journal of Rheumatology, 23, 1221-1226. Coakley, E. H., Kawachi, I., Manson, J. E., Speizer, F. E., Willett, W . C , & Colditz, G. A. (1998). Lower levels of physical function are associated with higher body mass index among middle-aged and older women. International Journal of Obesity, 22, 958-965. Colditz, G. A. (1999). Economic costs of obesity and inactivity. Medical Science in Sports and Exercise, 31 (Suppl. 11), S663-S667 Colditz, G. A., Willett, W . C , Rotnitsky, A., & Manson, J. E. (1995). Weight gain as a risk factor for clinical diabetes mellitus in women. Annals of Internal Medicine, 122, 4 8 1 ^ 8 6 . Colditz, G. A., Willett, W . C , Stampfer, M . J., Manson, J. E., Arkey, R. A., Hennekens, C. H., & Speizer, F. E. (1990). Weight as a risk factor for clinical diabetes in women. American Journal of Epidemiology, 132, 501-513. Cooper, C , Inskip, H., Croft, P., Campbell, L., Smith, G., McLaren, M., &c Coggon, D. (1998). Individual risk factors for hip osteoarthritis: Obesity, hip injury, and physical activity. American Journal of Epidemiology, 147, 516-522. Davis, M . A., Ettinger, W . H., Neuhaus, J. M., & Hauck, W . W . (1988). Sex differences in osteoarthritis of the knee: The role of obesity. American Journal of Epidemiology 127 1019-1030. Falkner, N . H., French, S. A., Jeffery, R. W., Neumark-Sztainer, D., Sherwood, N . E., &c Morton, N . (1999). Mistreatment due to weight: Prevalence and sources of perceived mistreatment in w o m e n and men. Obesity Research, 7, 572-576. Farrow, D. C , Weiss, N . S., Lyon, J. L., & Daling, J. R. (1989). Association of obesity and ovarian cancer in a case-control study. American Journal of Epidemiology, 129, 1300-1304. Field, A. E., Byers, T., Hunter, D. J., Laird, N . M., Manson, J. E., Williamson, D. P., Se Willett, W . C. (1999). Weight cycling, weight gain, and risk of hypertension in women. American Journal of Epidemiology, 150, 573-579. Fine, J. T., Colditz, G. A., Coakley, E. H., Moseley, G., Manson, J. E., Willett, W . C , & Kawachi, I. (1999). A prospective study of weight change and health-related quality of life in women. Journal of the American Medical Association, 282, 2136-2142. Flegal, K. M., Carol!, M . D., Kuczmarski, R. J., & Johnson, C. L. (1998). Overweight and obesity in the United States: Prevalence and trends, 1960-1994. International Journal of Obesity, 22, 39-47.
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Folsom, A. R., Prineas, R. J., Kaye, S. A., & Soler, J. T. (1989). Body fat disttibution and self-rep ed prevalence of hypertension, heart attack, and heart disease in older women. International Journal of Epidemiology, 18, 361-367. Fontaine, K., Cheskin, L., & Barofsky, I. (1996). Health-related quality of hfe in obese persons seeking treatment. Journal of Family Practice, 43, 265-270. Ford, E. S. (1999). Body mass index and colon cancer in a national sample of aduh U S men and women. American Journal of Epidemiology, 15, 390-398. Giovannucci, E., Ascherio, A., R i m m , E. B., Colditz, G. A., Stampfer, M . J., & Willett, W . C. (1995). Physical activity, obesity, and risk for colon cancer and adenoma in men. Annals of Internal Medicine, 122, 327-334. Giovannucci, E., R i m m , E. B., Chute, C. G., Kawachi, I., Colditz, G. A., Stampfer, M . J., & Willett, W . C. (1994). Obesity and benign prostatic hyperplasia. American Journal of Epidemiology, 140, 989-1002. Gorsky, R., Pamuk, E., Williamson, D. F., Shaffer, P., & Koplan, J. (1996). The 25-year health care costs of w o m e n w h o remain overweight after 40 years of age. American Journal of Preventative Medicine, 12, 388-394. Gortmaker, S. L., Must, A., Perrin, J. M., Sobol, A. M., & Dietz, W . H. (1993). Social and economic consequences of overweight in adolescence and young adulthood. Neuj England Journal of Medicine, 329, 1008-1012. Harris, T. B., Ballard-Barbasch, R., Madans, J., Makue, D. M., & Feldman, J. J. (1993). Overweight, weight loss, and risk of coronary heart disease in older women: The N H A N E S 1 Epidemiologic Follow-Up Study. American Journal of Epidemiology, 137, 1318-1327. Hart, D. J., & Spector, T. D. (1993). The relationship of obesity, fat distribution and osteoarthritis in w o m e n in the general population: The Chingford Study. Journal of Rheumatology, 20, 331-335. Hartz, A. J., Rupley, D. C , Kalkhoff, R. D., &c R i m m , A. A. (1983). Relationship of obesity to diabetes: Influence of obesity level and body fat distribution. Prevention Medicine, 12, 351-357. Holbrook, T. L., Barrett-Conner, E., & Wingard, D. L. (1989). The association of hfetime weight and weight control patterns with diabetes among men and w o m e n in an adult community. International Journal of Obesity, 13, 723-729. Huang, Z., Hankinson, S. E., Colditz, G. A., Stampfer, M . J., Hunter, D. J., Manson, J. E., Hennekens, C. H., Rosner, B., Speizer, F. E., & Willett, W . C. (1997). Dual effects of weight and weight gain on breast cancer risk. Journal of the American Medical Association, 278, 1407-1411. Huang, Z., Willett, W . C , Manson, J. E., Rosner, B., Stampfer, M . J., Speizer, F. E., & Colditz, G. A. (1998). Body weight, weight change, and risk for hypertension in women. Annals of Internal Medicine, 128, 81-88. Kuczmarski, R. J., Flegal, K. M., Campbell, S. M., & Johnson, C. L. (1994). Increasing prevalence of overweight among U S adults: The National Health and Nutrition Examination Surveys, 1960 to 1991. Journal of the American Medical Association, 272, 205-211. Kyogoku, S., Hirohata, T., Takeshita, S., Nomura, Y., Shigematsu, T., & Horie, A. (1990). Survival of breast-cancer patients and body size indicators. International Journal of Cancer, 46, 824-831. Lagergren, J., Bergstrom, R., & Nyren, O. (1999). Association between body mass and adenocarcinom a of the esophagus and gastric cardia. Annals of Internal Medicine, 130, 883-890. Larkin, J., &c Pines, H. (1979). N o fat person need apply. Sociology of Work and Occupations, 6, 312-327. Le Marchand, L., Wilkens, L. R., Kolonel, L. N., Hankin, J. H., & Lyu, L. C. (1997). Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Research, 57, 4787-4794. Levy, E., Levy, P., Le Pen, C , & Basdevant, A. (1995). Economic cost of obesity: The French situation. International Journal of Obesity, 19, 788-792. Lundgren, H., Bengtsson, C , Blohme, G., Lapidus, L., & Sjostrom, L. (1988). Adiposity and adipose tissue distribution in relation to incidence of diabetes in women: Results from a prospective population study in Gothenburg, Sweden. International Journal of Obesity, 13, 413-423. Maclure, K. M., Hayes, K. C , Colditz, G. A., Stampfer, M . J., Speizer, F. E., &c Willett, W . C. (1989).
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Relative weight, diet and risk of symptomatic gallstones in middle-aged women. New England Journal of Medicine, 321, 563-569. Mahler, R. J., &; Adler, M . L. (1999). Chnical review 102. Type 2 diabetes mellitus: Update on diagnosis, pathophysiology, and treatment. Journal of Clinical Endocrinology and Metabolism, 84, 1165-1171. M a n n , G. V. (1974). The influence of obesity on health. N e w England Journal of Medicine, 291, 178-185, 226-232. Manninen, P., Riihimaki, H., Hehovaara, M., & Makela, P. (1996). Overweight, gender and knee osteoarthritis. International Journal of Obesity, 20, 595-597. Manson, J. E., Colditz, G. A., Stampfer, M . J., Willett, W . C , Rosner, B., Manson, R. R., Speizer, F. E., &c Hennekens, C. H. (1990). A prospective study of obesity and risk of coronary heart disease in women. N e w England Journal of Medicine, 322, 882-889. Manson, J. E., Willett, W . C , Stampfer, M . J., Colditz, G. A., Hunter, D. J., Hankinson, S. E., Hennekens, C. H., & Speizer, F. E. (1995). Body weight and mortality among women. N e w England Journal of Medicine, 333, 677-685. Martinez, M . E., Giovannucci, E., Spiegelman, D., Hunter, D. J., Willett, W . C , & Colditz, G. A. (1997). Leisure-time physical activity, body size, and colon cancer in women: Nurses' Health Study research group. Journal of the National Cancer Institute, 89, 948-955. Mikhail, N., Golub, M . S., & Tuck, M . L. (1999). Obesity and hypertension. Progress in Cardiovascular Diseases, 42, 39-58. Missed opportunities in preventive counseling for cardiovascular disease—United States, 1995. (1998, February 13). Morbity and Mortality Weekly Report, 47, 91-95. Must, A., Jacques, P. F., Dallal, G. E., Bajema, C. J., & Dietz, W . H. (1992). Long-term morbidity and mortality of overweight adolescents: A follow-up of the Harvard Growth Study of 1922 to 1935. N e w England Journal of Medicine, 327, 1350-1355. Must, A., Spadano, J., Coakley, E. H., Field, A. E., Colditz, G. A., &c Dietz, W . H. (1999). The disease burden associated with overweight and obesity. Journal of the American Medical Association, 2 82, 1523-1529. Narbro, K., Jonsson, E., Larsson, B., Wedel, H., & Sjostrom, L. (1996). Economic consequences of sick-leave and early retirement on obese Swedish women. International Journal of Obesity, 20, 895-903. National Center for Health Statistics. (1996, June). Monitoring health care in America (Quarterly Fact Sheet). Rockville, M D : Author. National Heart, Lung, and Blood Institute (NHLBI). (1998). Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. Obesity Research, 6, 51S-209S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (2000a). Digestive disorders: Gallstones [Online]. Available: http://www.niddk.nih.gov/health/digest/pubs/gallstns/gallstns.hlm#whatare [2000, January 27]. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (2000b). National Diabetes Information Clearinghouse: Diabetes overview [Online]. Available: http://www.niddk.nih.govhealth/diabetes/pubs/dmover/dmover.html [2000, January 27]. Ohlson, L. O., Larsson, B., Svardsudd, K., Welin, L., Eriksson, H., Wilhelmsen, L., Bjorntorp, P., & Tibblin, G. (1985). The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes, 34, 1055-1058. Patient Information Resource. (2000). Prostate enlargement: Benign prostatic hyperplasia [Online]. Available: http://www.gretmar.com/webdoctor/BPHaAging.html [2000, January 31]. Peacock, S. L., White, E., Daling, J. R., Voigt, L. F., 8c Malone, K. E. (1999). Relation between obesity' and breast cancer in young women. American Journal of Epidemiology, 149, 339-346. Popkin, B. M . (1994). The nutrition transition in low-income countries: A n emerging crisis Nutrition Review, 52, 285-298. Rexrode, K. M., Carey, V. J., Hennekens, C. H., Walters, E. E., Colditz, G. A., Stampfer, M . J., Willett, W . C , &C Manson, J. E. (1998). Abdominal adiposity and coronary heart disease in women. Journal of the American Medical Association, 280, 1843-1848.
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Rexrode, K. M., Hennekens, C. H., Willett, W. C, Colditz, G. A., Stampfer, M. J., Rich-Edwards, J. W., Speizer, F. E., & Manson, J. E. (1997). A prospective study of body mass index, weight change, and risk of stroke in women. Journal of the American Medical Association, 277, 1539-1545. Rich-Edwards, J. W., Goldman, M . B., Willett, W . C , Hunter, D. J., Stampfer, M . J., Colditz, G. A., & Manson, J. E. (1994). Adolescent body mass index and ovulatory infertility. American Journal of Obstetrics and Gynecology, 171, 171-177. Rimm, E. B., Stampfer, M . J., Giovannucci, E., Ascherio, A., Spiegelman, D., Colditz G. A., & Willett, W . C. (1995). Body size and fat distribution as predictors of coronary heart disease among middle-aged and older U S men. American Journal of Epidemiology, 141, 1117-1127. Roe, D., & Eichwort, K. (1976). Relationship between obesity and associated health factors with unemployment among low income women. Journal of the American Medical Women's Association, 31, 193-204. Rumpel, C , Ingram, D. D., Harris, T. B., & Madans, J. (1994). The association between weight change and psychological well-being in women. International Journal of Obesity, 18, 179-183. Segal, L., Carter, R., & Zimmet, P. (1994). The costs of obesity: The Australian perspective. PharmacoEconomics, 5(Suppl. 1), 45-52. Seidell, J. C. (1995). The impact of obesity on health status: Some implications for health care costs. International Journal of Obesity, 19(Suppl. 6), 13-16. Seidell, J. C , Verschuren, W . M., van Leer, E. M., & Kromhout, D. (1996). Overweight, underweight, and mortality: A prospective study of 48,287 men and women. Archives of Internal Medicine, 156, 958-963. Shoff, S. M., & N e w c o m b , P. A. (1998). Diabetes, body size, and risk of endometrial cancer. American Journal of Epidemiology, 148, 234-240. Sonne-Holm, S., & Sorensen, T. I. (1986). Prospective study of attainment of social class of severely obese subjects in relation to parental social class, intelligence, and education. British Medical Journal, 292, 586-589. Stampfer, M . J., Maclure, K. M., Colditz, G. A., Manson, J. E., &c Willett, W . C. (1992). Risk of symptomatic gallstones in w o m e n with severe obesity. American Journal of Clinical Nutrition, 55, 652-658. Stevens, J., Cai, J., Pamuk, E. R., Williamson, D. F., Thun, M . J., & W o o d , J. L. (1998). The effect of age on the association between body-mass index and mortality. N e w England Journal of Medicine, 338, 1-7. Thompson, D., Edelsberg, J., Colditz, G. A., Bird, A. P., & Oster, G. (1999). Lifetime health and economic consequences of obesity. Archives of Internal Medicine, 159, 2177-2183. Tornberg, S. A., & Carstensen, J. M . (1994). Relationship between Quetelet's index and cancer of the breast and female genital tract in 47,000 w o m e n followed for 25 years. British Journal of Cancer, 69, 358-361. U.S. Department of Agriculture and U. S. Department of Health and H u m a n Services. (1995). Nutrition and your health: Dietary guidelines for Americans. Washington, D C : U.S. Government Printing Office. VanltaUie, T. B. (1979). Obesity: Adverse effects on health and longevity. American Journal of Clinical Nutrition, 32(Suppl.), 2723-2733. Vaughn, T. L., Davis, S., Fristal, A., & Thomas, D. B. (1995). Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiology, Biomarkers and Prevention, 4, 85-92. Wadden, T. A., & Stunkard, A. J. (1985). Social and psychological consequences of obesity. Annals of Internal Medicine, 103, 1062-1067. Willett, W . C , Dietz, W . H., & Colditz, G. A. (1999). Guidelines for healthy weight. N e w England Journal of Medicine, 341, 427-434. Wing, R. R., & Jeffery, R. W . (1995). Effect of modest weight loss on changes in cardiovascular risk factors: Are there differences between m e n and w o m e n or between weight loss and maintenance? International Journal of Obesity, 19, 67-73. Witteman, J. C. M., Willett, W . C , Stampfer, M . J., Colditz, G. A., Kok, F. J., Sachs, F. M., Speizer,
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F. E., Rosner, B., & Hennekens, C. H. (1990). Moderate alcohol consumption and increased risk of systemic hypertension. American Journal of Cardiology, 65, 633-637. Witteman, J C. M., Wihett, W . C , Stampfer, M . J., Colditz, G. A., Sacks, F. M., Speizer, F. E., Rosner, B., &c Hennekens, C. H. (1989). A prospective study of nutritional factors and hypertension among US women. Circulation, 80, 1320-1327. World Health Organization. (1998). Obesity: Preventing and managing the global epidemic. Report of a W H O Consultation on Obesity, Geneva, June 3-5, 1997 (Publication No. W H O / N U T / NCD/98.1). Geneva: Author. Yong, L. C , Kuller, L. H., Rutan, G., & Bunker, C. (1993). Longitudinal study of blood pressure: Changes and determinants from adolescents to middle age. The Dormont High School follow-up study, 1957-1963 to 1989-1990. American Journal of Epidemiology, 138, 973-983.
2
Body Weight Regulation: N e u r a l ,
Endocrine,
Autocrine
a n d
M e c h a n i s m s
S T R E A M S O N C. C H U A , JR. R U D O L P H L. LEIBEL
The biology of body weight regulation is complex and operates through effects on energy intake, energy expenditure, and caloric partitioning (i.e., the chemical composition of somatic energy stores). Body weight is maintained in a steady state by a balance between caloric intake and energy expenditure. Alterations of intake or expenditure are usually accompanied by compensatory changes in the other components of energy balance, tending thereby to maintain relative constancy of body weight and composition. The absolute caloric requirements for an organism are dependent on actual metabolic mass rather than absolute body mass. This is because some body compartments are less metabolically active, such as adipose tissue and bone, which are primarily composed of inert triglyceride and minerals, respectively. Furthermore, the various tissues have different qualitative and quantitative fuel requirements (Gallagher et al., 1998). Rates of fuel consumption per unit mass are higher in brain and heart than, for example, in skeletal muscle at rest. Thus body composition and the metabolic mass of specific organs are important factors in energy balance.
IS B O D Y W E I G H T R E G U L A T E D ? Experiments on animals (Hervey, 1988) and humans (Sims et al., 1973) suggest that absolute body weight is regulated (Leibel, Rosenbaum, & Hirsch, 1995). Weight loss induced by caloric restriction is countered by increased food intake and weight regain w h e n food is presented ad libitum. This phenomenon is also seen in growing organisms and is part of the biological response to deprivation-induced growth failure, termed catch-up growth. H o w ever, there are limits to "catch-up growth." Severe long-term caloric restriction of develop19
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ing organisms causes permanent, though not equivalent, stunting in all compartments of somatic mass (Hughes, 1982; W i d d o w s o n & M c C a n c e , 1975). Thus early environmental factors can exert powerful influences on adult body weight. Body weight gain can be induced by overfeeding and presenting highly palatable diets that induce hyperphagia (Levin, Dunn-Meynell, Balkan, & Keesey, 1997; Levin & Keesey, 1998). U p o n cessation of the overfeeding or the palatable diet, body weight loss occurs as a result of diminished intake or increased energy expenditure until the premanipulation weight is attained. However, long-term effects can be induced by early overnutrition of rodents during the preweaning phase of development (Johnson, Stern, Greenwood, Zucker, & Hirsch, 1973), leading to permanent excess adiposity in the aduh rat and associated metabohc changes, such as mild insuhn insensitivity (You, Gotz, Rohde, & Dorner, 1990). Dramatic alteradons in body mass can be achieved by mechanical or chemical lesions centered in the hypothalamus. Hyperphagia and obesity resuh from bilateral lesions of the medial hypothalamus (Hetherington & Ranson, 1940; Keesey & Hirvonen, 1997), affecting the ventromedial and arcuate nuclei. A similar syndrome of hyperphagia and obesity is observed in rodents and humans with mutations that inactivate genes whose products function as modulators of ingestive behavior and energy balance—for example, lepdn, leptin receptor (LEPR), neuropeptide Y (NPY), agouti gene-related pepdde ( A G R P ) , pro-opiomelanocortin ( P O M C ) , melanocortin receptor 4 ( M C 4 R ) , and cordcotropin-releasing hormone ( C R H ) (see Table 2.1). In contrast, aphagia and severe weight loss occur as a resuh of bilateral lesions of the lateral hypothalamic areas (Anand & Brobeck, 1951). This hypothalamic area contains neurons that secrete orexigenic peptides: melanin-concentradng hormone ( M C H ) and oxexin/hypocretin. These experimental observations indicate that body weight is regulated by a system coordinated in the central nervous system. However, tissue-specific growth also plays a role in the control of body composition (see Table 2.2). Several questions are raised by these simple observations: 1. Is the factor being regulated absolute body weight, a component of body mass, or total fuel stores? W h a t are the signals and the sensors for the regulated factor(s)? 2. Are each of the body compartments regulated independently, or are there systems that affect multiple tissues and organs? 3. Is there a hierarchy for preservation of these body compartments? 4. Are the metabolic pathways for response to weight loss and weight gain identical? 5. W h a t is the nature of the coupling a m o n g caloric intake, substrate partitioning, and energy expenditure? Since perfect couphng of the components of energy balance would result in the maintenance of a constant body weight and body composition, it is obvious that the coupling of the components of energy balance is imperfect.
Table 2.1. Genes Expressed in the Central Nervous System That Regulate Body Weight Orexigenic/anabolic molecules
Anorectic/catabolic molecules
Neuropeptide Y (NPY) Agouti gene-related peptide (AGRP) Agouti-related transcript (ART) Melanin-concentrating hormone (MCH) Dopamine
Leptin receptor (LEPR) Pro-opiomelanocortin (POMC) Melanocortin receptor 4 (MC4R) Corticotropin-releasing hormone (CRH) Serotonin receptor subtype 2C (5-HT2C) Glucagon-like peptide 1 receptor (GLP-IR)
Body Weight Regulation
21
Table 2.2. Genes Expressed in Peripheral Tissues That Regulate Body Weight Skeletal muscle
White adipose tissue
Myostatin ( M Y O ) Callipyge Ryanodine receptor 1 (RYRl) Myogenin Myogenic differentiation antigen 1 Myogenic factor 5 Myogenic factor 4
Leptin C C A A T enhancer-binding proteins—a, p, 8 (CEBP-a, CEBP-p, CEBP-8) Nuclear sterol regulatory-element-binding protein Ic (SREBP-lc) High-mobility group protein isoform I-C (HMGIC) Lipoprotein lipase (LPL) Fatty-acid-binding protein 4, expressed in adipocytes (aP2) Peroxisome proliferator-activated receptor gamma (PPARG) q^.
Brown adipose tissue
Uncoupling protein 1 (UCPl) Ch^lecystokinin receptor A (CCK-A) Bombesin receptor subtype 3 (BRS-3) Glucagon-like peptide 1 (GLP-1)
W H A T C O M P O N E N T S O F ENERGY BALANCE ARE REGULATED? In early studies of the effects of precise neuroanatomical lesions within the hypothalamus, gross alterations of body mass were produced in rats. Ventromedial lesions caused hyperphagia and severe obesity. Lesions of the lateral hypothalamic area caused hypophagia and profound weight loss. These studies led to a hypothesis of dual centers in the hypothalamus that controhed body weight (Elmquist, Elias, & Saper, 1999). The ventromedial hypothalamic area w a s viewed as a satiety center, whereas the lateral hypothalamic area was proposed as the "eating center." Debates ensued as to whether intrinsic neurons of the two areas or neuronal axons passing through these areas were the principal mediators of the apparent regulatory roles associated with the respective anatomical regions. Molecular genetic studies, which enable the disruption of specific neurotransmitters in specific cell bodies and their connections, have indicated that both intrinsic neurons and fibers of passage are important in mediating the effects of these two types of lesions (Elmquist et al., 1999). Neuroanatomical studies of neurochemically defined neuronal populadons (Elmquist et al., 1999) provide a detailed picture of the pathways that control energy balance.
R E G U L A T I O N O F B O D Y W E I G H T B Y SKELETAL M U S C L E M E T A B O L I S M By virtue of its mass, skeletal muscle mass accounts for a substantial portion of oxidative metabolism, even at rest. Skeletal muscle mass can increase by myocyte hypertrophy resulting from mechanical loads. O n the other hand, muscle mass can atrophy during unloading. Therefore, it is not surprising that several genes have been identified that directly affect muscle mass: myostatin ( M Y O ) , callipyge, and ryanodine receptor 1 (RYRl). These genes have apparent effects in multiple muscle groups and appear to aher body composition by increasing muscle mass and decreasing adipose tissue mass. A m e m b e r of the transforming growth factor family, M Y O is expressed early in development within skeletal muscle precursor cells that have a probable role of inhibiting m y ocyte growth and/or differentiation (Lee & McPherron, 1999). Mice and cattle without M Y O have increased skeletal muscle mass (Grobet et al., 1997; Kambadur, Sharma, Smith, & Bass, 1997; McPherron & Lee, 1997; Szabo et al., 1998). For M Y O - k n o c k o u t catde, the increase in muscle mass appears to be at the expense of other tissues, since the absolute weights of adipose tissue and all visceral organs are diminished. Although this phenomenon
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of "metabolic steal" has not been observed in MYO-knockout mice, further investigations are warranted to document this finding in cattle, in light of the fact that callipyge sheep (Cockett et al., 1996; Jackson, Miller, & Green, 1997) and RYRl-mutant pigs (Fuju et al., 1991; MacLennan, 1992) have increased muscle mass and diminished fat mass. Alleles of the R Y R l gene that cause malignant hyperthermia phenotype in humans and pigs also cause increased calcium release in myocytes, leading to increased expense of mechanical force during contractions (Gallant & Lentz, 1992; Reiss et al., 1991). Thus it is possible that humans w h o are susceptible to malignant hyperthermia m a y have increased muscle mass. A phenotypic test that can identify individuals (humans and pigs) susceptible to malignant hyperthermia has been verified by correlation with genotype at the R Y R l gene. The test relies on increased contractility of muscle upon exposure to caffeine and 4-chloro-mcresol in vitro (Baur et al., 2000). Unfortunately, there have been no reports regarding the effect of the R Y R l mutations on h u m a n body composition. Developmental factors contribute to the determination of skeletal muscle mass. N u merous transcription factors—for example, myogenin, myogenic differentiation antigen 1, myogenic factor 5, and myogenic factor 4—have been identified that are necessary for normal skeletal development (Hasty et al., 1993; Nabeshima et al., 1993; Rawls et al., 1998; Rudnicki et al, 1993). Although genetic ablations of these genes cause a profound reduction of skeletal muscle, and often a complete absence of skeletal muscle, the adult phenotype cannot be observed since the knockout mice die within a few minutes of birth, presumably due to an inability to initiate respiration. In the aggregate, these experimental observations indicate that skeletal muscle produces factors that affect skeletal muscle mass as well as other tissue compartments.
EFFECTS O F B R O W N A D I P O S E TISSUE O N B O D Y W E I G H T The brown adipose tissue (BAT) of small mammals is responsible for producing up to 50% of the energy required to maintain a constant body weight (Himms-Hagen, 1990). The control of nonshivering thermogenesis (NST) is exerted through sympathetic nervous system input to B A T . Therefore, it is not surprising that mice with a transgene that ablates B A T become obese (Loweh et al., 1993). B A T is ablated by producing the a chain of diphtheria toxin in B A T under the control of the uncoupling protein (UCP) promoter. If these mice are reared under thermoneutral conditions, preventing B A T deterioration and production of the toxin, the obese phenotype is not manifested. This indicates that the obesity is due to the loss of B A T and the concomitant decrease in energy expenditure (Klaus, Munzberg, Truloff, & Heldmaier, 1998; Melnyk, Harper, & Himms-Hagen, 1997). In transgenic mice, the loss of B A T is only partial and temporary, since B A T regenerates after inactivation of the toxic transgene. Surprisingly, mice with U C P l (the major U C P of B A T ) knocked out do not develop obesity or any alterations in food intake (Enerback et al, 1997). It is probable that other proteins compensate for the lack of U C P l . T w o proteins, U C P 2 and U C P 3 , appear to be homologous to U C P l . However, two lines of evidence suggest that this is unlikely. First, humans w h o are homozygous for a truncating mutation of U C P 3 are not uniformly obese (Chung et al, 1999). Second, sequence comparisons indicate that crucial histidine residues (145 and 147), which are required for the uncoupling activity of U C P l , are not conserved in U C P 2 and U C P 3 (Bienengraeber, Echtay, ?iC Klingenberg, 1998; Echtay, Bienengraeber, Winkler, & Klingenberg, 1998). It is possible that uncoupling proteins are not the sole mediators of N S T . Other mitochondrial molecules that can facilitate mitochondrial uncouphng m a y be identified.
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REGUIATION OF BODY WEIGHT BY WHITE ADIPOSE TISSUE DEVELOPMENT Development and Proliferation of White Adipose Tissue Lipodystrophy, the phenotype associated with a lack of some or all adipose tissue depots, consists of several distinct syndromes in humans. Lamin A/C gene mutations have been implicated in some humans (Cao & Hegele, 2000; Shackleton et al., 2000; Speckman et al., 2000). The mechanism, however, whereby a ubiquitously expressed nuclear membrane protein can cause a disease specific to white adipose tissue ( W A T ) remains to be identified. Mouse models of lipodystrophy have been generated by the expression of dominant negative proteins that inhibit the activities of transcription factors necessary for the differentiation of white adipocytes. O n e of these synthetic constructs, A-ZIP/F-1, encodes (1) a leucine zipper-dimerizing domain that forms heterodimers with C C A A T enhancer-binding proteins (CEBPs) and J U N s ; and (2) an acidic amphipathic helix that replaces the basic DNA-binding domain (McKnight, 1998). The heterodimers containing A-ZIP/F-1 are stable and devoid of DNA-binding and transcription-enhancing activities. The second synthetic construct, nuclear sterol regulatory-element-binding protein Ic (SREBP-lc), lacks the Golgi membrane attachment domain and is constitutively targeted to the nucleus (Shimomura et al., 1998). Nuclear SREBP-lc is a transcription factor that binds sterol regulatory elements. Mice expressing these transgenes have greatly diminished W A T and B A T , visceromegaly, hyperinsulinemia, and hyperglycemia. Lipodystrophic humans and rodents demonstrate increased metabolic rate, severe insulin resistance, and glucose intolerance as a result of the lack of W A T . Although m a n y of the manifestations of lipodystrophy, such as hyperphagia and altered insulin sensitivity, can be attributed to the lack of leptin secretion, the increased metabolic rate of lipodystrophy is not the result of leptin deficiency (see below). Thus W A T apparently produces a factor that regulates metabolic rate, or the loss of W A T alters metabolic pathways in such a w a y as to favor a catabolic state. CEBPs are a family of transcription factors necessary for the differentiation of preadipocytes to adipocytes. The CEBP-a form is expressed mainly in adipocytes. Mice with a homozygous knockout of the CEBP-a gene are nearly devoid of W A T and B A T (Wang et al., 1995). M o s t of the mice are born alive but die within a few hours of birth. Mice with combined mutations of the C E B P - ^ and CEBP-8 isoforms have a similar phenotype of reduced adipose tissue mass and increased neonatal mortality (Tanaka, Yoshida, Kishimoto, & Akira, 1997). Variant alleles of the peroxisome proliferator-activated receptor g a m m a ( P P A R G ) have been associated with obesity and/or diabetes (Barroso et al., 1999; Deeb et al., 1998). The P P A R G peptide forms a heterodimer with the retinoid X receptor (Kliewer, Umesono, N o o nan, H e y m a n , &C Evans, 1992) that binds prostaglandin J2 and the synthetic thiazolidinediones (Forman et al., 1995; L e h m a n n et al., 1995; Nagy, Tontonoz, Alvarez, Chen, & Evans, 1998). D u e to the insulin-sensitizing activity of thiazohdinediones and the association of activating mutations of P P A R G with diabetes and obesity, it is assumed that P P A R G is an important mediator of lipid accumulation in adipocytes. Mice with a homozygous deletion of P P A R G die during embryonic development (Barak et al., 1999; Miles, Barak, He, Evans, & Olefsky, 2000). However, mice with reduced P P A R G activity, by virtue of hemizygosity for a knockout allele of P P A R G , are protected from diet-induced obesity. O n a high-fat diet, the P P A R G hemizygotes had less adiposetissuemass than wild-type mice, although the adipocytes were larger. Adipocytes differentiate from a precursor cell, probably from a fibroblast/mesenchymal lineage. The high-mobility group protein isoform I-C ( H M G I C ) gene is induced in adiposetissueby feeding mice a high-fat diet (Anand & Chada, 2000), suggesting that it m a y
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be a marker for the differentiation pathway from preadipocyte to adipocyte. HMGIC is a m e m b e r of a family of proteins that stimulates the enhancer activity of transcription factor complexes. Mice with a targeted disruption of H M G I C are resistant to developing obesity on a high-fat diet and to the obesity induced by leptin deficiency. However, because H M G IC is expressed in stem cells that differentiate into multiple cell types, H M G I C deficiency results in a dwarf phenotype (Benson & Chada, 1994).
Leptin Secretion from WAT Leptin is an adipocyte hormone that is secreted primarily by adipocytes. The molecule, which is a m e m b e r of the cytokine superfamily, w a s identified by positional cloning of the ob/ob mouse (Lep°'') mutation (Zhang et al., 1994). Leptin concentrations in the blood are directly proportional to fat mass, and are modulated by nutritional state (Frederich et al., 1995; N a g y et al., 1997; Rosenbaum et al., 1996, 1997). Food restriction causes a rapid and large (-50%) decrease in circulating leptin concentrations, while overfeeding results in a small increase in leptin concentration. Leptin-deficient mice and h u m a n s are hyperphagic and develop early-onset obesity prior to the onset of sexual maturity (Montague et al., 1997; Ozata, Ozdemir, & Licinio, 1999). Indeed, the starvation response—an increase in food-seeking and ingestive behaviors, coupled with increased metabolic efficiency—is most likely mediated by the decrease in circulating leptin concentrations associated with caloric deprivation. Hormonal changes associated with starvation—such as decreases in gonadal steroids, thyroid hormones, growth hormones, follicle-stimulating hormone, and luteinizing hormone—are also due to diminished leptin action, since leptin replacement during fasting reverses these hormonal changes (Ahima et al., 1996). However, the metabolic and behavioral responses to elevated circulating concentrations of leptin are m u c h less dramatic. Hyperleptinemia, produced by leptin injections or with leptin gene transfer by adenovirus vectors, causes a reduction in body fat mass in normal animals (Ahima, Kelly, Elmquist, & Flier, 1999; Chen et al., 1996; M u o i o , D o h m , Tapscott, & Coleman, 1999). However, hyperleptinemia is observed in obese rodents and humans without abnormalities in leptin production or leptin signaling (Halaas et al., 1997; Heymsfield et al., 1999; Hinney et al., 1997). Thus the response to decreases in leptin signaling is robust, whereas hyperleptinemia is not necessarily associated with diminished fat mass. For organisms living in a constandy changing environment with fluctuating access to food, h could be argued that a response to hyperleptinemia that would reduce fat mass might be associated with reduced fhness and diminished capacity to survive bouts of restricted caloric availability, leading to evolutionary selection against such a response (Flier, 1998; Rosenbaum & Leibel, 1999). In some species, there are physiological circumstances in which extremely rapid fat accumulation is necessary for survival, such as the fattening periods prior to hibernation and longdistance migrations. Cessation of fat accumulation, caused by hyperleptinemia, would be counterproductive to survival. The obesity observed in leptin-deficient rodents is due mainly to the increased caloric intake. However, two other factors are contributory: diminished N S T (Trayhurn, Thurlby, & James, 1977) and preferential deposition of calories as fat (Coleman, 1985). The decreased N S T of mice is mainly due to diminished sympathetic stimulation of B A T (Blumberg, Deaver, & Kirby, 1999; Scarpace, Matheny, Pollock, & Tumer, 1997; Stehhng, Doting, Nuesslein-Hildesheim, Olbort, & Schmidt, 1997). As a consequence, the B A T of leptin-deficient mice is atrophic. However, prolonged stimulation with adrenergic agents, or by rearing at a decreased ambient temperature, can activate the B A T of leptin-deficient mice (Coleman, 1982; Smith & Romsos, 1984). The other contributory factor to the obesity of leptin-deficient mice is manifested as
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preferential deposition of ingested calories into triglyceride in adipose tissue (Coleman, 1985; M u o i o et al, 1999). T h e fractional body masses constituting brain mass and skeletal muscle mass are reduced in leptin-deficient mice, although the livers are enlarged due to increased triglyceride accumulation. T h e effect on body composition is most readily demonstrated in leptin-deficient mice that have been pair-fed with genetically normal controls, equalizing the caloric intake of the two genotypes. The pair-feeding paradigm produces leptin-deficient mice with a body mass that is only slightly greater than that of a genetically normal mouse. However, body composition analysis reveals that the pair-fed leptindeficient m o u s e has a significantly higher body fat content (i.e., - 4 0 % fat by weight in comparison to - 1 5 % in wild-type animals). Indeed, this fractional body fat content is not significantly different from leptin-deficient mice fed ad libitum, indicating that leptin deficiency affects ingestive behavior as well as the metabolic parameters that regulate body composition. Thus leptin or L E P R deficiency in rodents produces obesity via three mechanisms: (1) increased ingestion, (2) decreased N S T , and (3) preferential fat deposition. In humans, the rare inactivating mutations of these genes appear to produce obesity primarily through effects on food intake (Clement et al., 1998; Montague et al., 1997; Ozata et al, 1999; Ran, Reaves, O'Rahilly, & Whitehead, 1999). The reasons for these differences are not k n o w n , but m a y relate to the fact that leptin-deficient or LEPR-deficient rodents have hyperglucocorticoidemia, whereas h u m a n s do not. The obesity of leptin deficiency in mice is associated with a strain-dependent Type 2 diabetes mellitus syndrome of insulin resistance and altered insulin secretion that apparently has not been observed in leptin-deficient humans. In addition, leptin-deficient mice exhibit severe hypercorticism (Saito & Bray, 1983), an aspect of leptin deficiency that (as noted above) is not observed in leptin-deficient humans. Leptin deficiency in mice and h u m a n s has severe effects on hormonal status that result in hypothalamic hypogonadism and infertility, mild hypothyroidism, and mild growth hormone deficiency (Montague et al., 1997; Ozata et al., 1999). These neuroendocrine defects are manifest at the level of the hypothalamus, although it remains to be determined whether these are direct or indirect actions of leptin deficiency. Although two hormones, insulin and glucocorticoids, are the primary transcriptional regulators of leptin gene expression, promoting leptin synthesis and secretion (MacDougald, H w a n g , Fan, & Lane, 1995; Russell et al., 1998; Sivitz et al., 1998), the hexosamine biosynthetic pathway (Wang, Liu, Hawkins, Barzilai, & Rossetti, 1998) and its end product, urioline 5-diphosphate-N-acetylglucosamine, have been implicated in the tissue-specific regulation of leptin gene expression in adipocytes and skeletal muscle. Conditions that promote increased flux through the hexosamine pathway, such as hyperglycemia and hyperlipidemia, inhibit leptin synthesis in adipocytes but promote leptin synthesis in skeletal muscle. This would suggest that there are tissue-specific autoregulatory loops for leptin production and secretion. M o r e importantly, this pathway could account for the acute response of adipocytes to food deprivation.
Minor Effects on Body Weight by Disruption of Lipolysis The lipolytic pathway for the release of fatty acids into the circulation from adipocytes is well characterized. A fatty-acid-binding protein, specifically expressed in adipocytes (aP2), has been proposed as a fatty acid chaperone during lipolysis. Mice with genetic knockout of the aP2 gene have diminished lipolysis rates, both basal and isoproterenol-stimulated (Hotamisligil et al., 1996). T h e aP2-knockout mice are lean on normal c h o w and become obese on a high-fat diet, but they do not become diabetic or insulin-resistant w h e n obese. There is
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a partial compensation of fatty acid binding by overexpression of keratinocyte lipidprotein (Coe, Simpson, & Bernlohr, 1999). It is possible that the failure of aP2-knockout mice to develop insulin resistance on a high-fat diet is due to an alteration of the composition of circulating fatty acids (indirectly by alterations in fatty acid metabolism due to the aP2 deficiency). Although there are only minor differences between normal and knockout mice in total plasma free fatty acids, as well as fatty acid composition, (3-adrenergic stimulation in vivo causes significant changes in fatty acid composition. Deficiencies in either of two lipolytic enzymes, lipoprotein lipase (LPL) and hormonesensitive lipase (LIPE), cause hyperlipidemia and increased mortality. Mice that do not have LIPE (Osuga et al., 2000) are superficially normal, although the males are sterile. Without LIPE, mice have a normal amount of W A T , although adipocyte size is enlarged twofold. The B A T mass of LIPE-deficient mice is increased fivefold. Mice and humans without LPL suffer early mortality due to hyperchylomicronemia. The LPL-knockout mice can be rescued by a transgene expressing LPL in skeletal muscle only (Weinstock et al., 1995, 1997). The LPL-knockout mice appear to have fewer adipose tissue stores. However, numerous human cases of partial and complete LPL deficiency have been reported, and no clear association to obesity has been observed.
R E G U L A T I O N O F B O D Y W E I G H T BY THE H Y P O T H A L A M U S Mediation of Leptin's Actions by LEPR The LEPR is a member of the cytokine receptor superfamily and has a single transmembrane region (Tartaglia et al., 1995). The LEPR forms a homodimer, and each monomer is capable of binding one leptin molecule (Devos et al., 1997). There are binding sites for Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins, which are intracellular signal transducers of leptin (Baumann et al., 1996; Ghilardi et al., 1996; Vaisse et al., 1996). The LEPR gene encodes numerous isoforms (some of which are species-specific) with identical leptin-binding sites but different carboxyl termini due to splicing of alternative 3' terminal exons. There is a soluble receptor (LEPR-E) that does not contain a transmembrane domain and is highly expressed in the mouse placenta, leading to hyperleptinemia (Gavrilova, Barr, Marcus-Samuels, & Reitman, 1997) during pregnancy (i.e., up to a 100-fold increase in circulating leptin concentrations). However, this isoform accumulates in the blood only up to twofold during gestation in humans (Henson, Swan, & O'Neil, 1998) and rats (Kawai et al., 1997), suggesting that leptin's role during gestation may not be universal. The human LEPR gene has lost the polyadenylation signal in the 3' terminal exon for the LEPR-E form, indicating that soluble human LEPR is produced by cleavage of membrane bound LEPR isoforms (Chua et al., 1997). There are several membrane-bound isoforms—LEPR-A, LEPR-B, LEPR-C, LEPR-D, and LEPR-F—all of which contain the identical JAK docking she. However, only LEPR-B bears a S T A T docking motif. Moreover, loss of the LEPR-B isoform in the Lepr^'' mouse is sufficient to produce an obesity-diabetes syndrome that is identical to complete LEPR deficiency and leptin deficiency (Brown, Chua, Liu, Andrews, & Vandenbergh, 2000; Chen et al., 1996; Chua, Chung, et al., 1996; Chua, White, et al., 1996; Lee et al., 1996, 1997; Liu, Leibel, & Chua, 1998; Wu-Peng et al., 1997). Therefore, the genetic evidence indicates that leptin signals relevant to the obesity-diabetes phenotype are mediated by the LEPR-B isoform only, and that the JAK and S T A T proteins, rather than JAK proteins alone, initiate the intracellular signaling cascade. Other actions of leptin, such as stimulation of angiogenesis (Sierra-Honigmann et al.,
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1998) and immune responses (Lord et al., 1998), remain to be more fully explored in terms of signal transduction. Rodents with defective L E P R genes exhibit an obesity-diabetes syndrome that is identical to the syndrome caused by leptin deficiency (Argiles, 1989; Aubert, Herzog, Camus, Guenet, & Lemonnier, 1985; B r o w n et al., 2000; H u m m e l , Dickie, & Coleman, 1966; Koletsky, 1973; Leiter, Coleman, Eisenstein, & Strack, 1980). This includes (1) early-onset obesity associated with hyperphagia, decreased N S T , and preferential fat deposition; (2) neuroendocrine disturbances at the hypothalamic level; and (3) Type 2 diabetes associated with insulin resistance and defective insulin secretion. H u m a n s with L E P R deficiency (Clement et al., 1998) have hyperphagic obesity and neuroendocrine disturbances similar to those of LEPR-deficient rodents (but without insulin resistance or diabetes). Although L E P R is expressed in m a n y tissues with pleiotropic effects, its main site of action relevant to energy balance lies in the hypothalamus. This influence is supported by several lines of evidence: 1. Disruption of the STAT-signaling competent LEPR-B isoform, as observed in the Lepr''*' mouse, is sufficient to produce the obesity-diabetes syndrome of complete L E P R deficiency in the Lepr'^^^"^ mouse and the Lepr^''^ rat. 2. LEPR-B constitutes a major fraction of L E P R (up to 4 0 % ) expressed in the hypothalamus, whereas L E P R - B constitutes - 1 % of L E P R in almost every tissue except lymph nodes (Ghilardi et al., 1996). 3. Delivery of leptin to the brain, in doses too small to detect in the circulation, mimics the effects of physiological doses of leptin delivered to the periphery (Campfield, Smith, Guisez, Devos, &c Burn, 1995; Halaas et al., 1995; Pelleymounter et al., 1995). 4. Leptin administration causes the activation of the STAT-signaling pathway in the hypothalamus (Vaisse et al., 1996)—an effect that is not observed in peripheral tissues— and produces major alterations in the expression of neuropeptide genes, such as N P Y and P O M C (Baskin, H a h n , & Schwartz, 1999). LEPR is expressed within many neuronal cell types that are important in regulating ingestion, and the neuropeptide genes expressed within these neuronal types are modulated by leptin. Within the arcuate nucleus, N P Y / A G R P neurons (Broberger, Johansen, Johansson, Schalling, & Hokfelt, 1998; H a h n , Breininger, Baskin, & Schwartz, 1998; Wilson et al., 1999) and POMC/cocaine- and amphetamine-regulated transcript ( C A R T ) neurons (Ahima et al., 1999; Ehas et al., 1999; Korner, Chua, Williams, Leibel, & Wardlaw, 1999) express LEPR. The transcriptional activities of these neuropeptide genes appear to be regulated in part by leptin. Interestingly, the orexigenic peptides N P Y and A G R P are coexpressed within the same neurons, while the anorectic peptides P O M C and C A R T are coexpressed. Within the lateral hypothalamus, both M C H neurons and hypocretin/orexin neurons are regulated by leptin (Elias et al., 1998). Similarly, within the paraventricular nucleus, C R H (Schwartz, Seeley, Campfield, Burn, & Baskin, 1996) and thyrotropin-releasing hormone ( T R H ) (Legradi, Emerson, Ahima, Flier, & Lechan, 1997) neurons are sensitive to leptin. Physiological states associated with diminished circulating leptin concentrations, such as food restriction, are correlated with increased expression of the orexigenic peptides (NPY, A G R P , hypocretin/orexin, and M C H ) and diminished expression of the anorectic neuropeptides ( P O M C , C A R T , and C R H ) . Diminished leptin concentrations are associated with decreased T R H messenger R N A ( m R N A ) . Leptin administration during food restriction prevents m a n y of these fasting-associated changes of gene expression, indicating that the primary role of leptin m a y be to regulate the physiological response to diminished availability of calories and/or diminished triglyceride stores.
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Melanocortin System Regulation of Ingestion and Glycemic Control The POMC/CART neuron produces a-melanocyte-stimulating hormone (a-MSH) by processing of the prohormone P O M C (Eipper & Mains, 1980). Transcription of P O M C and secretion of its constituent peptides—7-MSH, a-MSH, adrenocorticotropic hormone (ACTH), and (B-endorphin, among others—are sensitive to nutritional state, decreasing under states of negative energy balance (Ahima et al., 1996; Elias et al, 1999; Korner, Chua, WiUiams, Leibel, & Wardlaw, 1999). The inactivation of the P O M C gene in mice (via gene knockout; Yaswen, Diehl, Brennan, & Hochgeschwender, 1999) and humans (via spontaneous mutations; Krude et al., 1998) results in an obese phenotype associated with adrenal insufficiency (i.e., loss of pituitary A C T H secretion) and with altered pigmentation. In the absence of M S H , melanin synthesis is channeled to produce pheomelanin, a yeUow to red pigment. The anorectic action of a - M S H is produced upon binding to and stimulation of M C 4 R , a typical G-protein-coupled receptor (Cone et al, 1996; Mountjoy, Robbins, Mortrud, & Cone, 1992). The loss of M C 4 R in mice (via knockout by gene targeting) produces obesity as well as insulin resistance and hyperglycemia (Huszar et al., 1997). However, pigmentation and adrenal steroid secretion in MC4R-deficient mice are unaltered due to the presence of other melanocortin receptors in melanocytes (MCIR, M S H receptor) and adrenocortical cells (MC2R, A C T H receptor). Due to their predominant locahzation to the arcuate nucleus, a medially located area of the hypothalamus, the P O M C / C A R T neurons are potential candidates for the satiety neurons that are ablated in ventromedial hypothalamic lesions. T w o endogenous antagonists of a - M S H have been identified as related proteins: agouti-signaling protein (ASP) (Bultman, Michaud, & Woychik, 1992) and AGRP/agoutirelated transcript (ART) (OUmann et al., 1997; Shutter et al., 1997). ASP interacts intermittently with a - M S H to produce an alternating pattern of eumelanin and pheomelanin stripes on the hair shafts of agouti-pigmented organisms (OUmann, Lamoreux, Wilson, & Barsh, 1998). However, gain-of-function mutations that cause ectopic overexpression of agouti produce hyperphagia, obesity, moderate insulin resistance, and a yellow coat whose intensity is proportional to the degree of ASP expression (Miltenberger, Mynatt, Wilkinson, & Woychik, 1997; Yen, GiU, Frigeri, Barsh, & Wolff, 1994). Alterations of body temperature and N S T are not prominent and do not contribute significantly to the obese phenotype in yellow mice with this mutation. Moreover, the obesity produced by agouti overexpression is late in onset and accompanied by increased linear growth, in contrast to the obesity of leptin and LEPR deficiency. This is also true of MC4R-deficient children: They are chubby and tall, and have advanced bone ages with increased bone mineral density (Ho & MacKenzie, 1999; Vaisse, Clement, Guy-Grand, & Froguel, 1998; Yeo et al., 1998). Thus the obesity produced by inhibition of M C 4 R appears to be primarily the resuh of hyperphagia. A G R P is a neuropeptide that colocalizes with N P Y within neuronal ceO bodies in the arcuate nucleus (Broberger et al., 1998). A G R P is an antagonist of M S H action at M C 4 R , and overexpression of A G R P produces hyperphagia and obesity. However, there are no effects on pigmentation, since A G R P (unlike ASP) does not bind to M C I R . Hypothalamic NPY and Its Receptors
NPY is a 36-amino-acid neurotransmitter, widely distributed in the central and periph nervous systems, that was identified by virtue of its amidated tyrosine residues at both the amino and carboxy termini (Tatemoto et al., 1985). Intracerebral injections of N P Y strongly stimulate ingestion in multiple species. Chronic treatment causes weight gain and relative insulin insensitivity (Beck, Stricker-Krongrad, Nicolas, &c Burlet, 1992; Zarjevski, Cusin,
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Vettor, Rohner-Jeanrenaud, & Jeanrenaud, 1993). The concentrations of NPY mRNA are stimulated during conditions of negative energy balance, such as fasting and diabetes (Chua, Brown, et al., 1991; Chua, Leibel, & Hirsch, 1991; Jhanwar-Uniyal & Chua, 1993; Kowalski et al., 1999). N P Y is a mediator of leptin's actions in the hypothalamus. Leptinand LEPR-deficient rodents have increased hypothalamic N P Y , whereas N P Y deficiency makes leptin-deficient mice less obese (Erickson, HoUopeter, & Palmiter, 1996), concordant with the orexigenic actions of N P Y and its increased expression in leptin-deficient mice. Although little or no deficit of ingestive behavior is seen in NPY-deficient animals, Yl-receptor-knockout animals become mildly obese and hyperinsuhnemic (Kanatani et al., 2000; Kushi et al., 1998). These findings suggest that compensatory changes allow for the loss of N P Y activity, whereas loss of crucial Y I and Y 2 receptors, but not Y 5 receptors, results in deficits in feeding and metabolism (Marsh, HoUopeter, Kafer, & Palmiter, 1998; Naveilhan et al., 1999).
The MCH Neurons of the Lateral Hypothalamus MCH was identified as a potential neuropeptide that regulates ingestion because of its increased expression as found by differential display in the hypothalamus of leptin-deficient mice (Qu et al., 1996). Initially identified by its actions on melanosomes in amphibian melanocytes, the orexigenic properties of M C H were confirmed upon central injection of M C H into rodents (Nahon, 1994; Q u et al., 1996). Mice that are deficient in M C H show diminished body weight and hypophagia, leading to a decreased adipose tissue mass. There are no alterations in body temperature in these animals, indicating that thermogenesis is minimally affected. The receptor for M C H , somatostatic like receptor 1 (SLC-1), is a m e m ber of the superfamily of G-protein-coupled receptors with strong homology to the somatostatin receptor (Chambers et al., 1999; L e m b o et al., 1999; Saito et al., 1999; Shimomura et al., 1999). The widespread distribution of the m R N A and the protein for SLC-1 provide support for the effects of M C H on ingestion, sexual behavior, learning, and modulation of the stress response.
CENTRAL N E R V O U S SYSTEM C O N T R O L O F INGESTION Dopaminergic Pathways A long-standing debate regarding the role of intrinsic neurons andfibersof passage in the development of aphagia and adipsia in rodents with bilateral lateral hypothalamic lesions may have been resolved by transgenic techniques. As the M C H - k n o c k o u t mice are hypophagic, so are mice that are deficient in dopamine (Zhou & Palmiter, 1995). The production of mice with isolated dopamine deficiency required sophisticated genetic manipulations, since dopamine is also the metabolic precursor of norepinephrine and epinephrine. A two-step process was necessary: (1) The tyrosine hydroxylase locus was inactivated, preventing the synthesis of all catecholamines; and (2) introduction of the tyrosine hydroxylase complementary D N A under the control of the dopamine-(3-hydroxylase locus allowed synthesis of catecholamines (other than dopamine) in ceUs that normally produce norepinephrine and epinephrine. Interestingly, treatment with levodopa (L-dopa) partially corrected the hypophagia and poor weight gain of these animals. However, it remains unclear whether a parkinsonian-like movement disorder was caused by the genetic manipulation. A movement disorder m a y interfere with the locomotor components of feeding rather than with ingestive drive per se. Further analysis, however, of the dopamine-deficient mice suggests that their
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ingestive drive is reduced even after L-dopa treatment (Szczypka et al., 1999). Similarly, loss of dopaminergic transmission by lateral hypothalamic lesions, or by chemicals that disrupt dopaminergic neurons, might induce a movement disorder rather than a specific effect on appetitive behavior. M a n y of the genes encoding the large family of dopamine receptors have been genetically ablated. Mice with a knockout of individual dopamine receptors do not manifest hypophagia or hypodipsia: D j (Xu et al, 1994), D j (Baik et al., 1995; Maldonado et al., 1997), D 3 (Xu et al., 1997), and the dopamine transporter (Jones et al., 1999). Therefore, it remains to be conclusively shown that loss of dopaminergic activity and transmission has a specific effect on ingestive behavior, independent of its effects on motor control.
Serotonergic Pathv/ays Serotonin has been implicated in body weight regulation (Simansky, 1996). Furthermore, weight gain during treatment with antidepressants that interfere with serotonin's activity has been widely observed (Vickers, Chfton, Dourish, & Tecott, 1999). Tricyclic antidepressants enhance the sensitivity of postsynaptic receptors (Chaput, de Montigny, & Blier, 1991), whereas selective serotonin reuptake inhibitors, such as sibutramine, antagonize the negative feedback effect of serotonin on presynaptic receptors. D u e to the large number of serotonin receptors, the receptors responsible for the effects of serotonin on ingestive behavior have been difficult to identify with pharmacological agents. Molecular genetic ablation of one receptor subtype, serotonin receptor subtype 2 C (5-HT2c), results in obese mice that are prone to seizures (Tecott, Logue, Wehner, & Kauer, 1998). The obesity is produced primarily by hyperphagia, since pair-feeding mutant mice with wild-type mice results in m u tant mice with normal body weights and normal body composition. Thus pharmacological agents that do not interfere with the 5-HT2C receptor might have minimal effects on body weight gain. Conversely, agents that selectively activate 5-HT2C m a y be efficacious compounds for appetite suppression and weight loss.
R E G U L A T I O N BY THE G U T The gut is able to sense the presence of ingested calories and to generate signals leading to meal termination (Smith & Romsos, 1984). Therefore, h is not surprising that the release of endogenous gut factors can modulate meal size. Molecular genetic data analysis has identified two receptors that mediate satiety signals: the A receptor for cholecystokinin (CCK-A) (Moran & Schwartz, 1994) and the bombesin receptor subtype 3 (BRS-3) (Fathi et al., 1996). A rat model of obesity, the Otsuka Long-Evans Tokushima Fatty ( O L E T F ) rat, is characterized by obesity associated with large meals and resistance to the satiating effects of C C K - A (Moran, Katz, Plata-Salaman, & Schwartz, 1998). These rats have an inactivating mutation within the C C K - A receptor gene (Funakoshi et al., 1995; M o r a n et al., 1998). The phenotype of delayed satiety is commensurate with the postulated function of the C C K - A receptor. However, other associated genetic alterations in the O L E T F rat strain m a y interact with the C C K - A receptor mutation to produce obesity, since inactivating mutations of the C C K - A receptor in humans and mice (Kopin et al., 1999) are not associated with obesityGenetic ablation of the BRS-3 gene produces hyperphagic mice (Ohki-Hamazaki et al., 1997) that do not display any other alterations in other components of energy homeostasis. Pair-feeding of the mutant mice, compared to normal controls, completely normalizes the body composition of the BRS-3-deficient mice. However, the endogenous ligand for the
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BRS-3 molecule remains to be identified, as mice with genetic ablations of the mammalian homologues of bombesin-like ligands and receptors—gastrin (Friis-Hansen et al., 1998), gastrin receptor ( W a n g & Dockray, 1999), gastrin-releasing peptide receptor (Hampton et al., 1998), and neuromedin B receptor (Ohki-Hamazaki et al., 1 9 9 9 ) — d o not develop obesity. The glucagon gene encodes glucagon and a splice variant, glucagon-like peptide 1 (GLP-1). A receptor for GLP-1 (GLP-IR) has been identified in the hypothalamus. Treatment with GLP-1 inhibits feeding, while exendin, a long-acting inverse agonist of GLP-IR, stimulates feeding (Larsen, Tang-Christensen, & Jessop, 1997; Turton et al., 1996). Despite these observations, mice with a targeted knockout of G L P - I R do not exhibit obesity or hyperphagia, even w h e n fed a high-fat diet (Scrocchi et al., 1996). The GLP-1 R-knockout mice do exhibit glucose intolerance with a glucose challenge, and in vitro testing supports the requirement of GLP-1 and G L P - I R for the stimulation of insulin release from beta cells exposed to glucose.
SUMMARY The range of molecules and cell types committed to the regulation of energy homeostasis is large and still only partly k n o w n . F r o m a physiological perspective, this plethora of agents and pathways clearly reflects the critical nature of this process for organismic survival and ability to reproduce, and for the diverse systems that participate in a coordinated w a y to determine body energy stores (e.g., ingestive behavior, nutrient partitioning, energy expenditure). The rodent mutations with the most striking impact on body fatness (e.g., ob and db) have effects on all three of these compartments. Genetic alterations affecting single compartments generally produce less striking phenotypic effects. The redundancy of the pathways, and the ability of one "limb" of control to compensate for changes in another (e.g., decline in energy expenditure with decreased metabolic fuel flux), provide a caution to those endeavoring to interrupt these pathways for therapeutic purposes. Better understanding of the full panoply of molecules and pathways, however, should ultimately permit very specific manipulations of energy intake and expenditure without substantial counterresponses by the organism.
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O b e s i t y
p. A. TATARANNI ERIC RAVUSSIN
Throughout evolution, humans and animals have evolved redundant mechanisms promoting accumulation of fat during periods of feast to survive periods of famine. However, what was an asset during evolution has become a liability in the current "pathoenvironment" (Ravussin, 1995). With the recent abrupt change in environmental conditions, in which high-fat food is constantly available and in which there is little need for physical activity, obesity has reached epidemic proportions in industrialized countries and in urbanized populations around the world (World Health Organization, 1998). In the United States in the late 1990s, one out of two adult Americans w a s overweight and one out of four was obese (Mokdad et al., 1999). M o r e alarming, the prevalence of obesity is drastically increasing a m o n g children (Troiano & Flegal, 1998). The World Health Organization (1998) has identified obesity as one of the major emerging chronic diseases. Obesity increases the risk for a number of noncommunicable diseases (e.g.. Type 2 diabetes, hypertension, dyslipidemias) and reduces life expectancy (Must et al., 1999). In the United States alone, the yearly cost of obesity to the public health system is estimated to be close to $100 billion. This represents between 5 % and 1 0 % of the U.S. health care budget (Wolf & Colditz, 1996). Obesity results from a chronic imbalance between energy intake and energy expenditure. Hyperphagia, a low metabolic rate, low rates of fat oxidation, and impaired sympathetic nervous system (SNS) activity characterize animal models of obesity. Similar metabolic factors have been found to characterize humans susceptible to weight gain. Recent research has provided an unprecedented expansion of our knowledge about the molecular mechanisms that m a y underlie such metabolic risk factors. Perhaps the greatest impact has resulted from the cloning of genes corresponding to several mouse monogenic obesity syndromes, and the subsequent characterization of the pathways involved. Three of these genes (ob, db, and A>') have aheady led to potential drugs (leptin) or drug targets (leptin receptor, melanocortin receptor 4 [ M C 4 R ] , neuropeptide Y [NPY] Y I and Y 5 receptors, and others) currently in pharmaceutical development. Over the past 15 years, w e and others have focused on understanding h o w m u c h of the 42
Energy Metabolism and Obesity
43
genetic predisposition to obesity, estimated to explain as much as 70% of body mass index (BMI) variability (Stunkard, Harris, Pedersen, & McClearn, 1990), is related to energy m e tabolism in humans. In this chapter w e review the current knowledge of the role of daily energy expenditure and its major components in the etiology of obesity.
METHODS OF MEASURING DAILY ENERGY EXPENDITURE Several methods have been developed to measure daily energy expenditure. The most accurate methods involve continuous measurements of heat output (direct calorimetry) or gas exchange (indirect calorimetry) in subjects confined in metabolic chambers. Because confined subjects are unable to pursue habitual activities, a number offieldmethods have been developed to measure energy expenditure in free-living condhions, including factorial methods, heart rate monitoring, body weight clamping, and the doubly labeled water method; because the last of these has proven to be the most satisfactory, it is discussed in more detail than the others.
Direct Calorimetfy Total heat loss from the body can be assessed by direct calorimetry. This method has been extensively applied to animal studies and, in a few instances, to h u m a n studies (Benzinger & Kitzinger, 1963; Spinnler, Jequier, Favre, Dolivo, & Vannotti, 1973; W e b b , 1985). The technique of direct calorimetry requires placing an individual in a small chamber in which all the heat released in the form of either dry or evaporative heat is measured. Dry heat loss represents the heat dissipated by convection and radiation, whereas evaporative heat loss is related to the evaporation of water from the lungs and skin. Direct calorimeters have been useful for validating other indirect methods, but they have become largely obsolete because they are very expensive and require the confinement of subjects in a very small room.
Indirect Calorimetry Under normal physiological conditions, neither oxygen nor carbon dioxide is stored within the body. Therefore, an indirect method of assessing energy expenditure is to measure oxygen consumption, carbon dioxide production, and nitrogen excretion. Protein oxidation is estimated on the basis of urinary nitrogen excretion. A nonprotein respiratory quotient (nonprotein VC02/nonprotein V O 2 ) can be calculated, and the ratio between carbohydrate and lipid oxidation can be assessed (Jequier, Acheson, & Schutz, 1987). W h e n the amount of each energy substrate oxidized (i.e., carbohydrate, fat, and protein) is known, it is possible to calculate the energy generated as a function of these oxidative processes. Indirect calorimetry has proved useful for the study of energy expenditure and/or substrate oxidation in normal and diseased states. Early measurements were performed on individuals wearing mouthpieces or face masks, which were later replaced by ventilated hood systems. The latter systems have the advantage of being easily tolerated for several hours. During the past two decades, the indirect calorimetry method has been applied to respiratory chambers (Dauncey, Murgatroyd, &C Cole, 1978; D u U o o et al., 1988; Jequier & Schutz, 1983; Mingheh, Schutz, Charbonnier, Whitehead, & Jequier, 1990; Ravussin, Lillioja, Anderson, Christin, & Bogardus, 1986; Rumpler, Scale, Conway, & M o e , 1990; V a n Es et al., 1984). These are rooms large enough (12,000-40,000 liters) for a subject to live in comfortably for up to several days. The measurements from the chamber are accurate and are n o w used extensively to assess the determinants of daily sedentary energy expenditure in hu-
PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY O F OBESIF/
44
mans. Respiratory chambers enable us to measure the different components of energy expenditure, including the sleeping metabolic rate, the energy cost of arousal, the thermic effect of food (TEF), and the energy cost of spontaneous physical activity (Figure 3.1). The only disadvantage is the confinement of the subjects in a relatively small room. Indirect Methods Used in Free-Living Conditions Because confined subjects are unable to pursue habitual activities, several field methods have been developed to measure energy expenditure in free-living conditions. The factorial method is based on estimates of energy expenditure from the time spent in various activities and their energy cost (Durnin & Passemore, 1967). This method, which is very timeconsuming and interferes with the daily routine, has been both criticized (Garrow, 1974) and defended (Durnin, 1978). Variations in the method occur because of differences in recording and describing activities, as well as in assigning energy costs to these activities. Comparisons of factorial methods against other field methods have provided reasonable or good agreement for groups but not for individuals (Acheson, Campbell, Edholm, Miller, & Stock, 1980; Borel, Riley, & Snook, 1984; Bradfield, Huntzicker, & Fruehand, 1969; Durnin, 1959; Edholm, 1973; Geissler, Dzumbira, & Noor, 1986). The heart rate method relies on intraindividual calibrations of heart rate against energy expenditure and is reasonably accurate only for the estimation of moderate to high levels of energy expenditure (Bradfield, 1971). Finally, a very indirect assessment of energy expenditure has been developed using weight maintenance energy intake over a period of weeks, in conjunction with the determination of changes in body composition (Leibel &c Hirsch, 1984; Weigle, 1988; Weigle, Sande, Iverius, M o n s e n , & BrunzeU, 1988). With this technique, the best estimates have been obtained for subjects on liquid formula diets.
C 0) Q. X 0) E> c 0 'm T3
Spontaneous Physical Activity Thermic Effect of Food
50
Arousal
>k 0) XI E (0
(0 •o •a 0 o SMR RMR 0) 25 o J5 .c I •D Q. C >, 0) CD 3 0 -^ > O Q F I G U R E 3.1. Components of daily energy expenditure in humans. Daily energy expenditure can be divided into three major components: the resting metabolic rate ( R M R — s u m of the sleeping metabolic rate [SMR] and the energy cost of arousal), which represents 5 0 % - 7 0 % of daily energy expenditure; the thermic effect of food, which represents - 1 0 % of daily energy expenditure; and the energy cost of physical activity (sum of spontaneous physical activity and unrestricted/voluntary physical activity), which represents 2 0 % - 4 0 % of daily energy expenditure.
Energy Metabolism and Obesity
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Doubly Labeled Water Technique The doubly labeled water method was developed in animals by Lifson (1966) and first used m h u m a n subjects by Schoeller and V a n Santen (1982). It is based on indirect calorimetry assumptions and on the differential elimination of deuterium (^H) and >»oxygen (^^O) from body water foUowing a loading dose of the two stable isotopes. Since the '^O is in equihbriu m with the water pool and the bicarbonate pool, the disappearance rates of the two isotopes measure the turnover of water (for ^H) and water plus carbon dioxide (for i^Q), from which carbon dioxide production is calculated by difference. Energy expenditure is then caL culated from carbon dioxide production by classical indhect calorimetric equations. The major advantage of the doubly labeled water method is that it provides an integrated measure of total carbon dioxide production over periods of 5 to 20 days, requiring only periodic sampling of urine for measurements of ^ H and i^O enrichments. Subjects can be studied in the free-living state and are not influenced or limited in their activity by wearing cumbersome monitors. This noninvasive method has been validated repeatedly and can be used for pregnant women, infants, chUdren, and elderly individuals (Coward et al., 1984; Jones et al., 1987; Klein et al., 1984; Ravussin, Harper, Rising, & Bogardus, 1991; Roberts, Coward, Schlingenseigpen, Nohria, & Lucas, 1986; SchoeUer & W e b b , 1984; Schoeller et al., 1986). In conjunction with other determinations of resting or sedentary energy expenditure using indirect calorimetry, this n e w method represents the best and most accurate w a y of assessing the energy cost of physical activity in people (see Figure 3.1). The major drawbacks are the high costs of the ^^O isotope (and its limited availability) and of the isotope ratio mass spectrometer necessary to determine the isotopic enrichments of ^ H and ^^O.
C O M P O N E N T S O F E N E R G Y EXPENDITURE: R E L E V A N C E T O OBESITY Knowledge of daily energy requirements in humans is a prerequisite for understanding how obesity might develop from a chronic energy imbalance (Durnin, Edholm, Miller, & Waterlow, 1973). Sedentary daily energy requirements can be accurately measured in a respiratory chamber. Since 1985, w e have used a respiratory chamber to perform measurements of 24-hour sedentary energy expenditure on more than 900 individuals (Weyer, Snitker, Rising, Bogardus, & Ravussin, 1999). These data firmly estabhsh that sedentary daily energy expenditure is a linear function of body size; that is, heavier people have higher metabolic rates than lighter people (Figure 3.1). Because a higher body weight can only be maintained by matching energy expenditure with intake, these data also give little credence to studies showing no correlation or negative correlation between energy intake and body weight (Heymsfield et al., 1995; Lichtman et al, 1992). The variability in daily energy requirements is related to the variability in energy expended for the three major components of daily energy expenditure: resting metabolic rate ( R M R ) , thermogenesis, and physical activity (Figure 3.1).
Resting Metabolic Rote The R M R is the energy expended by a subject resting in the fasting state under comfortable ambient conditions. R M R includes the cost of maintaining the integrated systems of the body and the homeothermic temperature at rest. In most sedentary adults, R M R accounts for approximately 6 0 % - 7 0 % of daily energy expenditure (Ravussin, LUhoja, et al., 1986). The close correlation between R M R and body size has been k n o w n for m a n y years and
46
PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY OF OBESITY
has formed the basis for the development of widely used equations to predict RMR from height and weight (Boothby & Sandiford, 1922; Cunningham, 1991; Harris & Benedict, 1919; Roza & Shizgal, 1984; Schofield, 1985). W e and many others, however, have shown that at any given body size, R M R can vary as much as 2 0 % among individuals. In our search for the possible mechanisms underlying the intersubject variability in R M R , we have explored the impact of body composition, gender, physical training, age, muscle metabohsm, SNS activity, and body temperature on R M R . In a study of 130 siblings from 54 Pima Indian famihes, we have shown that R M R correlated best with fat-free mass (Bogardus et al., 1986). In white volunteers, we found that females had a lower R M R when compared to males (-100 kcal/day less), independent of differences in fat-free mass, fat mass, and age (Ferraro et al., 1992). This might have been due to the effect of sex hormones on metabolic rate. Whether level of physical activity and training are determinants of the R M R remains controversial (Davis et al., 1983; Donahoe, Daria, Kirschenbaum, & Keesey, 1984; HUI, Sparling, Shields, & Heller, 1987; Lennon, Nagle, Stratment, Shrago, & Dennis, 1985; Poehlman, Melby, & Bradylak, 1988; Schulz, Nyomba, Alger, Anderson, & Ravussin, 1991; Stern et al., 1980; Tremblay, Nadeau, Fournier, & Bouchard, 1988; Tremblay et al., 1986). Cross-sectional studies of R M R indicate significant age-related declines (Boothby, Berkson, & Dunn, 1936; Shock & Yiengst, 1955; Vaughan, Zurlo, & Ravussin, 1991). Based on longitudinal data. Keys, Taylor, and Grande (1987) estimated that the decline in R M R was less than l % - 2 % per decade from the second to the seventh decade of hfe. Subsequent work has supported Keys and colleagues' conclusion that the decrease in R M R seen in elderly people can be explained largely by decreases in fat-free mass (Calloway & Zanni, 1980; Cohn et al., 1980; Tzankoff & Norris, 1977). Data from studies using indirect assessment of SNS activity suggest that the SNS may be involved in the regulation of R M R under eucaloric conditions (Saad et al., 1991; Schwartz, Jaeger, & Veith, 1988). Using a more direct measurement (microneurography), we found that the variability in energy expenditure was related to the variability of muscle sympathetic nerve activity (Spraul et al., 1993). Resting skeletal muscle metabohsm seems also to be a significant determinant of whole-body metabolism (Kirkwood, Zurlo, Larson, & Ravussin, 1991; Zurlo, Larson, Bogardus, & Ravussin, 1990), and recent studies suggest that uncoupling protein 3 (UCP3) expression appears to underlie some of this variability (Schrauwen, Xia, Walder, Snitker, & Ravussin, 1999). Finally, we have observed that variability in R M R , after adjustments for differences in fat-free mass, fat mass, and age, was related to the variability in body temperature in males (Rising, Keys, Ravussin, & Bogardus, 1992). These results indicate that body temperature could be a marker for a high or low relative metabohc rate. It is not clear whether the heat production in the body (i.e., the metabolic rate) is regulated to maintain a given "preset" temperature, or whether the temperature is simply a reflection of the equilibrium between the heat-producing and heat-losing mechanisms that are controlled by other factors. Fat-free mass, fat mass, age, and sex are the major determinants of R M R , explaining - 8 0 % of its variance (Jequier & Schutz, 1983; Ravussin, LUhoja, et al., 1986). However, some of the remaining variance is explained by family membership, suggesting that R M R is at least partly genetically determined (Bogardus et al., 1986). Further support for a genetic determinant of R M R comes from studies of twins by Bouchard and coUeagues (1989). Thermic Effect of Food
The TEF (i.e., the increase in energy expenditure observed after the administration o meal) accounts for approximately 5 % - 1 5 % of the daily energy expenditure (Tataranni, Larson, Snitker, & Ravussin, 1995; Weststrate, 1993). M a n y factors influence TEF: meal
Energy Metabolism and Obesity
47
size and composition; palatability of the food; time of the meal; and the subject's genetic background, age, physical fitness, and sensitivity to insulin. Brundin, Thorne, and W h a r e n (1992) have shown that T E F is also a function of the heat leakage across the abdominal wall, which is inversely related to the thickness of the abdominal adiposetissuelayer. These influences, plus technical aspects such as the position of the subject and the duration of measurement, m a k e T E F the most difficult-to-measure and the least reproducible component of daily energy expenditure (Tataranni et al., 1995; Weststrate, 1993). T E F has long been regarded as a component of daily energy expenditure that could cause significant variations in daily energy balance and therefore predispose individuals to obesity. T E F m a y have evolved as a mechanism for enriching protein-poor diets by disposing of the excess nonessential energy (DuUoo & Jacquet, 1999; Stock, 1999). Consequently, Stock (1999) and D u U o o and Jacquet (1999) have recently argued that large interindividual differences in TEF can only be uncovered under conditions of overfeeding with protein-depleted diets. However, given adequate protein and other essential nutrients in the diet, one can safely state that individual differences in T E F can account for only small differences in daily energy expenditure. Although a review of the published literature suggests that obesity m a y be associated with an impaired T E F (de Jonge & Bray, 1997), it is important to note that numerous studies have been published showing either a defect (Pittet, Chappuis, Acheson, de Techtermann, &c Jequier, 1976; Ravussin et al., 1983; Schwartz, Halter, & Bierman, 1983; Schutz, Golay, Felber, & Jequier, 1984; Segal, Gutin, N y m a n , & Pi-Sunyer, 1985; Thorne, HaUberg, & W a h r e n , 1989) or no defect in T E F in obese versus lean subjects (Blaza & Garrow, 1983; D'Alessio et al., 1988; Ravussin, Acheson, Vernet, Danforth, & Jequier, 1985; Schwartz, Ravussin, Massari, O'ConneU, & Robbins, 1985; Thorne, Naslund, &; Wahren, 1990; W e U e & C a m p b e U , 1983). Furthermore, in our prospective study, w e found no relationship between T E F and weight change in more than 100 subjects (Tataranni et al., 1995). Decreased thermogenesis is therefore a very unlikely explanation for significant degrees of obesity.
Physical Activity Physical activity, the most variable component of daily energy expenditure, can account for a significant amount of calories in very active people. However, sedentary adult individuals exhibk a range of physical activity that represents only 2 0 % - 3 0 % of total energy expenditure. Reduced physical activity as a cause of obesity is an obvious and attractive hypothesis. The energy expended in physical activity is quite variable, and the secular increase in obesity parallels the increase in sedentary hfestyles. Prentice and Jebb (1995) have presented evidence that in the U n h e d Kingdom, the prevalence of obesity has increased dramatically over the past three decades, despite a marked decrease in energy intake (Scalfi, Cohorti, & Contaldo, 1991). They resolve this paradox by hypothesizing that physical activity has decreased even more during the same period; they provide data using a proxy for activity (or inactivity), such as the numbers of hours of television viewing and the number of cars per household, both of which have increased continuously over the same period. (See Blair & Leermakers, Chapter 13, this volume, for more on exercise and weight management.) However, until the relatively recent introduction of the doubly labeled water method for measuring energy expenditure in free-living condhions (Schoeller & Field, 1991; Schoeller & van Santen, 1982), there has been no satisfactory method by which to assess the impact of physical activity on daily energy expenditure. Schulz and Schoeller (1994) have provided data on more than 2 0 0 subjects and have observed a wide variability in total energy expenditure, and therefore in physical activity. Using the ratio between total energy expenditure and R M R
48
PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY O F OBESITY
as an index of the level of physical activity (Figure 3.1), they have also shown that physical activity is decreased in heavier or fatter subjects. In a review of 574 doubly labeled water measurements. Black, Coward, Cole, and Prentice (1996) compUed data to (1) establish the limits of sustainable h u m a n energy expenditure; (2) establish the average and range of habitual energy expendhure in relationship to age and sex; and (3) describe the lifestyles and activity patterns associated with different levels of physical activity. Prentice, Black, Coward, and Cole (1996) described the relationship between graded levels of obesity and free-living energy expenditure in m e n and w o m e n of affluent societies, and confirmed that habitual total energy expenditure is increased with obesity because of concomitant increase in fat-free mass. They also suggested that except in massive obesity, the level and cost of physical activity are quite similar at different levels of body weight and B M I . This, however, does not exclude the possibility that an inactive lifestyle m a y be an important risk factor for the development of obesity. Whether a low level of physical activity is a cause or a consequence of obesity can only be tested in prospective studies. Prospective studies are providing initial evidence that even differences in nonvolitional muscle activity (i.e., fidgeting, muscle tone, maintenance of posture, etc.) m a y be important in determining predisposition to obesity and/or resistance to diet-induced weight gain (Levine, Eberhardt, & Jensen, 1999).
ENERGY BALANCE EQUATIONS The balance between energy intake and energy expenditure determines energy stores. Since living organisms must obey the first law of thermodynamics, the energy balance equation has been used to predict changes in body weight w h e n energy intake or expenditure is changed. However, the classic equation of energy balance, which states that the body energy store is equal to energy intake minus energy expenditure, has provided both insight and confusion in the understanding of energy balance in humans. M u c h of the confusion comes from inappropriate energy calculations using the static equation of energy balance (see below).
Equation during Weight Maintenance Energy Intake = Energy Expenditure This equation is self-evident and quite accurate under conditions of weight maintenance, as only limited changes in body composition are possible without changing body weight. It has been most useful in uncovering problems with reported energy intake. M o s t dietary intake studies show either no correlation or a negative correlation between energy intake and body weight (Lichtman et al, 1992; Romieu et al., 1988). This is in marked contrast to studies of energy expenditure, where there is a positive relationship (Figure 3.2). In addition to then greater fat mass, obese individuals have a greater fat-free mass, which is the main determinant of both R M R and 24-hour metabolic rate as measured in a respiratory chamber (Ravussin, LiUioja, et al., 1986). Studies involving free-living individuals have simultaneously measured energy expenditure via the doubly labeled water technique and energy intake via continuous recording of diet diaries (Bandini, Schoeller, Cyr, & Dietz, 1990; Mertz et al., 1991; Prentice et al., 1986). Under these careful conditions of food intake assessment, the obese subjects reported only one-half to two-thhds of then total energy intake; by contrast, lean subjects reported 8 0 % - 1 0 0 % (Lichtman et al. 1992). This gap between'the food that obese people perceive themselves eating and what they actually eat has been termed the
Energy Metabolism and Obesity
49
4500 4000 •o Q 3500 u 3000 s 3 2500 c a a. 2000 X 1500o >> ra 1000 o 500c o
40
20
60 80 fat-free mass (kg)
24-h e n e r g y expenditure
100
120
Total variance (SO) = 422
Determinant
Residual variance p-value
24-EE = 696
+ 18.9 FFM (kg)
Vmse 224
<0.0001
(kcal/d)
+ 10.0 FM(kg)
178
<0.0001
+ 180 male
165
<0.0001
-1.9 age(y)
164
<0.001
+ 7.1 W T R (decimal)
163
<0.05
+ 44 Pima Indian
162
<0.001
H G U R E 3.2. Relationship between 24-hour energy expenditure (24-EE) and fat-free mass (FFM) in over 900 subjects. The 24-hour energy expenditure was measured after at least 3 days on a weightmaintaining diet (50% carbohydrate, 30% fat, 20% protein) and FFM was assessed by hydrodensitometry or dual energy X-ray absorptiometry (DEXA). FFM is the major determinant of 24-hour energy expenditure, explaining a large proportion of its variance. Other determinants of 24-EE include tat mass (FM), waist-to-thigh ratio (WIR), sex, age, and race. From Weyer, Snitker Rising, Bogardus, and Ravussin (1999). Copyright 1999 by the Nature Publishing Group. Reprinted by permission.
"eye-mouth gap" and represents a major challenge for psychologists and psychiatrists interested in obesity and food intake.
Static Energy Balance Equation Change in Energy Stores = Energy Intake - Energy Expenditure This is the most common equation used in discussions and calculations of energy balance. Intuitively, it seems valid; however, Alpert (1990) has elegantly demonstrated that this
50
PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY O F OBESITY
equation is inadequate for calculations on living organisms, because k does not take into account the increasing energy expenditure with increasing weight (Jequier & Schutz, 1983; Ravussin, LUlioja, et al, 1986; Weyer et al., 1999). Thus a small initial increase in energy intake sustained over a number of years cannot lead to a large weight gain, as is often claimed.
Dynamic Energy Balance Equation Rate of Change of Energy Stores = Rate of Energy Intake - Rate of Energy Expenditure The use of "rates" in this equation introduces time dependency, thereby allowing the effect of changing energy stores (especially fat-free mass and weight) on energy expenditure to enter into the calculation (Alpert, 1990). This explains w h y a small initial positive energy balance (e.g., from an increased energy intake or a lower T E F ) wiU not lead to large weight increases over a number of years. After a short period of positive energy balance, the energy stores (fat mass and fat-free mass) wUl increase and cause an increase in energy expenditure (Figure 3.2), which wUl balance the increased energy intake. The individual will then once again be in energy balance, but with a higher energy intake, higher energy expenditure, and higher energy stores. Weight gain can therefore be viewed not only as the consequence of an initial positive energy balance, but also as the mechanism by which energy balance is eventually restored. H o w is intake balanced against expenditure, and h o w might a chronic mismatch between the two occur? A fruitful approach to these questions has been to dissect the energy balance equation into its various nutrient balance equations.
NUTRIENT BALANCE If the origins of a positive energy balance lie in the chronic imbalance of energy intake and expenditure, an appropriate question is this: " W h a t conditions allow a long-lasting imbalance between intake and expenditure?" A n examination of each nutrient balance equation to determine whether a chronic imbalance between nutrient intake and oxidation exists is only valid if each nutrient has a separate balance equation, implying separate regulation (Figure 3.3). In practical terms, is each nutrient either oxidized or stored in its o w n compartment (separate regulation), or does it get converted into another compartment for storage? This applies particularly to the issue of whether dietary carbohydrate is stored as fat (de novo lipogenesis). In contrast to animals (Zelewski & Swierczynki, 1990), de novo lipogenesis is very limited in humans and occurs only w h e n large excesses of carbohydrate are ingested (Acheson, Schutz, Bessard, Flatt, & Jequier, 1987; Acheson et al., 1988; Chascione et al., 1987; Just, Messing, Darmaun, Rongier, & Carmillo, 1990; Manji, Shikora, M c M a hon, Blackburn, & Bistrian, 1990). Because de novo lipogenesis does not occur in humans under physiological conditions, h seems reasonable to consider each nutrient balance equation as a separate entity.
Protein Balance Protein intake is usually about 15% of daily calories, and the protein stores in the body represent about one-third of the total stored calories in a 70-kg m a n . The daily protein intake amounts to a little over 1 % of the total protein stores (Bray, 1991; Snyder et al., 1974) (Fig-
Energy Metabolism and Obesity
51
Stores
Range > 60,000 kcal
Intake as total kcal 1,000
Esssa-*—
^R^^^S^^^^S^SSSCcncroccrocTO !CTO R8SSS9SSSSS990oooooooooooooo5ooo R89S999999SSS99ooooooooooooooooo< §§§8888888888888888888§§§§8§§§§ R8|8gsss99oo8888888888888888P^^'
Oxiciation as % stores
• p>Mf>Mfi
500
1.3
1,000
50
0.8
FIGURE 3.3. The daily nutrient balance of a 70-kg m a n (20% body fat) in relationship to nutrient stores, macronutrient intake, and macronutrient oxidation. Each nutrient intake and oxidation on a 2,500-kcal/day diet ( 4 0 % fat, 4 0 % carbohydrate, 2 0 % protein) is shown on the left as absolute intake in kilocalories and on the right as a percentage of its respective nutrient store. The ranges for each of the nutrient stores are shown and are based on values for a 70-kg m a n (20% body fat) and a 150-kg man (50% body fat). The fat stores for a 150-kg m a n are more than five times those of a 70kg man and extend far beyond the top of the diagram.
ure 3.3). The protein stores increase in size in response to such growth stimuli as growth hormone, androgens, physical training, and weight gain, but do not increase simply from increased dietary protein. Protein stores are thus tightly controlled, and on a day-to-day basis protein balance is achieved (Abbott et al., 1988). Therefore, protein imbalance cannot be implicated as a direct cause of obesity, although (as with the other nonfat nutrients) protein intake m a y affect the fat balance equation (Snyder et al, 1974).
Carbohydrate Balance Carbohydrate is usually the main source of dietary calories, yet the body stores of glycogen are very limited: 500-1,000 g, o n average (Acheson et al., 1988). Daily intake of carbohydrate corresponds to about 5 0 % - 1 0 0 % of the carbohydrate stores, compared to about 1 % for protein and fat (Schutz, Flatt, & Jequier, 1989) (Figure 3.3); over a period of hours and days, therefore, the carbohydrate storesfluctuatemarkedly compared with those of protein and fat. However, as with protein stores, they are tightly controlled (Rising, Keys, et al., 1992). Whether this control is based on humoral and/or nervous signals exchanged between the muscle and liver and the brain remains to be established. Dietary carbohydrate stimulates both glycogen storage and glucose oxidation and suppresses fat oxidation (Flatt, Ravussin, Acheson, & Jequier, 1985). That which is not stored as glycogen is oxidized (not converted to fat), and carbohydrate balance is achieved (Abbott et al., 1988; Flatt et al., 1985). Therefore, as with the other nonfat nutrients, a chronic imbalance between carbohydrate intake and oxidation cannot be the basis of weight gain. Storage capacity is hmited and controlled; conversion to fat is an option that only occurs under extreme conditions in humans; and oxidation is increased to match intake.
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PREVALENCE, C O N S E Q U E N C E S , A N D ETIOLOGY O F OBESITY
Fat Balonce In marked contrast to the other nutrients, body fat stores are large, and fat intake has no influence on fat oxidation (Flatt et al., 1985; Schutz et al., 1989). A s with protein, the daily fat intake represents less than 1 % of the total energy stored as fat, but the fat stores contain about six times the energy of the protein stores (Bray, 1991) (Figure 3.3). These fat stores are the energy buffer for the body, and the slope of the relationship between energy balance and fat balance is determined by conditions of day-to-day small positive or negative energy balances (Abbott et al., 1988). A defich of 200 kilocalories (kcal) of energy over 24 hours means that 2 0 0 kcal comes from the fat stores, and the same holds true for an excess of 200 kcal of energy, which ends up in the fat stores. Even in conditions of spontaneous overfeeding the entire excess fat intake is stored as body fat (Rising, Alger, et al., 1992). Ingestion of a mixed meal is followed by an increase in carbohydrate oxidation and a decrease in fat oxidation and the addition of extra fat does not alter that mix of nutrient oxidation (Flatt et al., 1985; Schutz et al., 1989). W h a t promotes fat oxidation, if it is not dietary fat intake? The amount of total body fat exerts a small but significant effect on fat oxidation, and this promotion of fat oxidation at higher body fat levels m a y represent a mechanism for attenuating the rate of weight gain (Zurlo, Lillioja, et al., 1990). Energy balance is the driving force for fat oxidation (Abbott et al., 1988; Zurlo, Lillioja, et al., 1990); w h e n it is negative (i.e., energy expenditure exceeding intake), fat oxidation increases. In summary, w h e n one considers energy balance in h u m a n s under physiological conditions, fat is the only nutrient that maintains a chronic imbalance between intake and oxidation, thus directly contributing to the increase in adipose tissue. The other nutrients will indirectly influence adiposity by their contribution to overall energy balance, and thus to fat balance, as emphasized by Frayn (1995). The use of the fat balance equation instead of the energy balance equation offers a n e w framework for understanding the pathogenesis of obesity.
Alcohol Balance There is an inconsistent relationship between reported alcohol intake and BMI, with many studies showing a negative relationship (Colditz et al., 1991; Hellerstedt, Jeffery, & Murray, 1990). However, h has been shown that in healthy individuals the fate of ingested alcohol is oxidation and not storage (as fat), and therefore perfect alcohol balance is achieved (Shelmet et al., 1988). In the same manner as dietary carbohydrate and protein, alcohol diverts dietary fat away from oxidation and toward storage, and k inhibits lipolysis. Therefore, a chronic imbalance between alcohol intake and oxidation cannot be a direct cause of obesity, although by contributing to overall energy balance, it m a y indirectiy influence fat balance. (For further reading on the nutrient content of foods, see Appendix 12.1 in Melanson & Dwyer, Chapter 12, this volume.)
METABOLIC RISK FACTORS FOR BODY WEIGHT GAIN IN ADULTS An understanding of the etiology of human obesity demands longitudinal studies. Crosssectional studies have added httie to our understanding of the physiological mechanisms predisposing to weight gain (Ravussin & Swinburn, 1993). Cross-sectional studies can only provide associations, whereas longitudinal studies reveal predictors or risk factors. Several studies have examined these predictors in the Pima Indian population in Arizona. Obesity is extremely prevalent a m o n g the Pima; therefore, weight gain is very c o m m o n in young
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adults, m a k i n g this g r o u p well suited for longitudinal studies of various metabolic risk factors of weight gain (Knowler et al., 1 9 9 1 ) .
Low Metabolic Rate Because obesity is associated with high absolute metabolic rate, both in resting conditions and over 2 4 hours (Ravussin, Lillioja, et al., 1 9 8 6 ; W e y e r et al., 1 9 9 9 ) , it cannot be caused by a l o w absolute metabolic rate, as is often proposed. M a n y investigators w h o have studied energy expenditure in h u m a n s have suggested that in the absence of a clear defect in energy expenditure in obese subjects, obesity can only be the result of excessive energy intake. H o w e v e r , the scatter a r o u n d the regression line between metabolic rate a n d b o d y size suggests that at a n y given b o d y size, individuals can have a "high," "normal," or " l o w " relative metabolic rate. This concept is expressed graphically in Figure 3.4. F r o m our o w n studies in adult nondiabetic P i m a Indians, w e found that a l o w relative metabolic rate (resting and 24-hour), adjusted for differences in fat-free m a s s , fat mass, age, a n d sex, w a s a risk factor for b o d y weight gain (Ravussin et al., 1988). After 4 years of follow-up, the risk of gaining 1 0 k g w a s approximately eight times greater in subjects with the lowest R M R (lower tertile) than in those with the highest R M R (higher tertUe) (Figure 3.5). According to a recent meta-analysis of published studies, formerly obese subjects have a 3 % - 5 % lower m e a n relative R M R than control subjects, w h i c h is likely to contribute to the high rate of weight regain in formerly obese persons (Astrup et al., 1999).
40 • •Low' R M R (-200 kcal/day) -^'Normal' R M R (predicted) •*-"Hlgti' R M R (+200kcal/d) c 03 '(0 O O c +^
> c •D 0) O > m E o 3 o
Time (years) FIGURE 3.4. Cumulative incidence of a 10-kg body weight gain for a subject with a "high" relative metabolic rate (200 kcal/day above that predicted for body size and body composition), for a subject with a "normal" R M R (equal to that predicted), and for a subject with a "low" R M R (200 kcal/day below that predicted). The cumulative incidence was calculated on the basis of follow-up data obtained in 126 Pima Indians followed for an average of 3 years via a survival analysis (proportional hazard linear model). Note that subjects with a "low" R M R had approximately eight times the risk of gaining weight compared to those with a "high" R M R had.
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3000-
B 2500C 0) X T3 LU :^ ^ O
2000-
CNJ 1500-
40
Fat
\ 60 Free M a s s (kg)
80
FIGURE 3.5. Relationship between 24-hour energy expenditure and fat-free mass derived from a large population. This figure represents values for different subjects. In terms of the absolute 24-hour energy expenditure, lean person A has a low value, while obese person B has a high value. In terms of relative 24-hour energy expenditure, both A and B fall on the regression line and are normal. Subjects C and D are of similar body size, but C has a relatively low metabolic rate and subject D has a relatively high metabolic rate. Subject C is at the greatest risk of developing obesity, but upon weight gain, the low relative metabolic rate becomes normalized (arrow).
Nevertheless, these data need to be interpreted with caution. First, in our studies, the variability of baseline energy expenditure accounted for only 1 6 % of the variability of weight gain. Second, theoretical estimates suggest that only 3 0 % - 4 0 % of the increase in body energy stores in people w h o gained weight can be attributed to the baseline defich in energy expenditure. These results could indicate that a low metabolic rate m a y also be a marker for abnormal regulation of dietary intake. Finally, a relatively low energy expenditure does not seem to be a predictor of weight gain in other adult populations (Weinsier et al., 1995).
L o w Physical Activity Another component of 24-hour energy expenditure is the energy cost of spontaneous physical activity, which accounts for 8 % - 1 5 % of total daily expenditure (Ravussin, LUhoja, et al., 1986). Consistent with the cross-sectional observation of decreased spontaneous physical activity in obese subjects, our longitudinal studies showed (1) that even in the confined envhonment of a respiratory chamber, spontaneous physical activity is a famUial trait; and (2) that a low level of spontaneous physical activity is associated with subsequent weight gain in males, but not in females (Zurlo et al., 1992). A recent study found that resistance to the development of obesity might be due to the ability of increasing spontaneous physical activity (also defined as nonexercise activity thermogenesis) in response to overfeeding (Levine et al., 1999). O f course, prospective studies in which
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free-living physical activity is measured (via the doubly labeled water technique) are needed to objectively assess what most scientists believe—that a low level of physical activity is a major predisposing factor for weight gain in individuals and in populations (Sundquist & Johansson, 1998).
Low Rates of Fat Oxidation The composition of nutrient intake has been shown to be an important factor in the genesis of obesity; consequently, one might expect that the composition of nutrient oxidation would also play a role. T h e nonprotein respiratory quotient, which is an index of the ratio of carbohydrate to fat oxidation, ranges from a value of about 0.80 after an overnight fast when fat is the main oxidative substrate (McNeil, Bruce, Ralph, & James, 1988) to values close to 1.00 after a large carbohydrate meal w h e n glucose is the major substrate (Flatt et al., 1985). Apart from the effect of diet composition, the respiratory quotient is also influenced by recent energy balance (i.e., negative balance causes more fat oxidation), sex (i.e., females tend to have reduced fat oxidation), adiposity (i.e., higher fat mass leads to higher fat oxidation), and family membership, suggesting genetic determinants (Frayn, 1995). Toubro, Sorensen, Hindsberger, Christensen, and Astrup (1998) confirmed that substrate oxidation rates, measured by respiratory quotient, exhibit familial aggregation after adjustment for energy balance, sex, and age. In a longitudinal study in Pima Indians, a high 24-hour respiratory quotient predicted weight gain (Zurlo, LUlioja, et al., 1990). Those in the 90th percentile for respiratory quotient (i.e., "low fat oxidizers") had a 2.5 times greater risk of gaining 5 kg or more body weight than those in the 10th percentile (i.e., "high fat oxidizers"). This effect was independent of a relatively low or high 24-hour metabolic rate. SimUar results were found in European American volunteers participating in the Baltimore Longitudinal Study on Aging (Seidell, Muller, Sorkin, &c Andres, 1992). In support of these observations, others have demonstrated that formerly obese volunteers have high respiratory quotients (i.e., low rates of fat oxidation) (Astrup, B u e m a n n , Christensen, & Toubro, 1994; Larson, Ferraro, Robertson, & Ravussin, 1995), and that those w h o are able to maintain weight loss have lower respiratory quotients than do those experiencing weight relapse (Froidevaux, Schutz, Christin, & Jequier, 1993).
Insulin Sensitivity Insulin sensitivity is measured as the total glucose disposal stimulated by insulin during a glucose clamp and is the s u m of carbohydrate oxidation and nonoxidative glucose disposal (mainly storage). Since higher rates of carbohydrate oxidation (as measured by the 24-hour respiratory quotient) predict weight gain, w e investigated whether insulin sensitivity would also predict weight gain in Pima Indians. Subjects in the 90th percentUe (most insuUn-sensitive) were approximately four times m o r e likely to gain 10 kg or more body weight than were those in the 10th percentile (most insulin-resistant), and this effect w a s more closely related to the oxidative than to the nonoxidative component of glucose metabolism (Swinburn et al., 1991). Thus insulin sensitivity predicts weight gain, or, conversely, insulin resistance is associated with significantly lower rates of weight gain. Similar observations were reported in Mexican Americans from the San Antonio Heart Study (Valdez et al., 1994) and in European Americans from the San Luis Valley Diabetes Study (Hoag, MarshaU, Jones, & H a m m a n , 1995). Yost, Jensen, and Eckel (1995) also reported that increased insulin sensitivity predicts weight regain following sustained weight loss. At least in adults, it appears that insulin resistance is a mechanism counteracting further weight gain (Eckel, 1992).
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Low SNS Activity Studies in European Americans indicate that the activity of the S N S is related to the three major components of energy expenditure: (1) R M R (Spraul et al., 1993); (2) T E F (Schwartz et al., 1988); and (3) spontaneous physical activity (Christin, O'ConneU, Bogardus, Danforth, & Ravussin, 1993). W e have recently shown that S N S activity is also negatively correlated with the 24-hour respiratory quotient (Snitker, Tataranni, & Ravussin, 1998). Further indications of the possible role of S N S activity in the regulation of energy balance in humans comes from a study showing that low S N S activity was associated with a poor weight loss outcome in obese subjects treated with diet (Astrup et al., 1995). Furthermore, Pima Indians, w h o are prone to obesity, have low rates of muscle sympathetic nerve activity compared to weight-matched European Americans (Spraul et al, 1993). In a prospective study, w e found that baseline urinary excretion rate of norepinephrine, a global index of S N S activity, was negatively correlated with body weight gain in male Pima Indians (Tataranni, Young, Bogardus, & Ravussin, 1997). Thus low S N S activity is associated with the development of obesity.
Low Plasma Concentration of Leptin Leptin, the product of the ob gene, is a hormone produced by the adipose tissue that inhibits food intake and increases energy expenditure (Caro, Sinha, Kolaczynski, Zhang, & Considine, 1997). T o investigate whether individuals prone to weight gain are hypoleptinemic, w e measured fasting plasma leptin concentrations in two groups of weight-matched, nondiabetic Pima Indians followed for approximately 3 years, 19 of w h o m subsequently gained weight (average weight gain 23 kg) and 17 of w h o m maintained their weight within 0.5 kg. After adjustment for initial percentage of body fat, m e a n plasma leptin concentration was lower in those w h o gained weight than in those whose weight was stable (Ravussin et al., 1997). Despite the leptin resistance apparent in obesity (Caro et al., 1997), these data indicate that relatively low plasma leptin concentrations m a y play a role in the development of obesity in some Pima Indians. O f note, relative hypoleptinemia is not a risk factor for obesity in other populations (Lissner et al., 1999; McNeely et al., 1999).
M E T A B O L I C RISK F A C T O R S F O R B O D Y W E I G H T G A I N IN C H I L D R E N One of the most troubling aspects of the current epidemic of obesity (Mokdad et al., 1999) is the increasing prevalence of obesity and Type 2 diabetes a m o n g chUdren. Childhood obesity is a very serious problem because tracking of overweight, albeit moderate, is observed between childhood and adulthood (Serdula et al., 1993). Furthermore, duration of obesity is an independent predictor of health outcomes (McCance et al., 1994). The risk of developing obesity seems to be especially elevated during early infancy, the adiposity rebound period during prepubertal growth, and the adolescent growth phase (Dietz, 1994). The observation that obesity occurs more frequently in children of obese parents has led to various studies to determine h o w m u c h of the genetic predisposition to obesity is related to energy metabohsm. Stunkard, Berkowitz, StaUings, and SchoeUer (1999) reported data on energy intake and energy expenditure in infants born to lean and overweight mothers; they concluded that excessive energy intake, rather than low energy expenditure, is the cause of obesity in infants at high risk of obesity. This is a vastly unexplored area, and more studies are needed to understand h o w eating behavior forms and solidifies in conjunction with thefinalmaturation of the h u m a n brain from childhood to adulthood. In their study
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of 18 subjects, Roberts, Savage, Coward, Chew, and Lucas (1988) measured energy expenditure by doubly labeled water in infants at 3 months of age and divided them post hoc into overweight and normal-weight groups at age 12 months. Energy expenditure (mostly activity) was on average 2 0 % lower in those w h o became overweight at 12 months than in those w h o did not. SimUarly, Griffiths, Payne, Stunkard, Rivers, and C o x (1990) reported that low energy expenditure in 5-year-old girls was negatively correlated with B M I at adolescence. In girls, reduction in total energy expenditure as a result of a marked reduction in physical activity during prepubertal growth has recently been reported (Goran, Gower, Nagy, & Johnson, 1998). However, other studies have faded to confirm that resting energy expenditure, total energy expenditure, or activity energy expenditure measured in early childhood is inversely related to the development of obesity (Goran, Hunter, Nagy, & Johnson, 1997; Johnson et al., 1999). Despite these large inconsistencies in the literature, it seems reasonable to conclude that a sedentary lifestyle in early childhood should be discouraged, because low levels of aerobic fitness (Johnson et al., 1999), excessive T V viewing (Robinson, 1999; Salbe, Weyer, FontvieUle, & Ravussin, 1998), and limited playing time (Salbe et al., 1998) have all been associated with increased risk of weight gain. S o m e studies have suggested that higher plasma insulin concentration early in life m a y predispose to obesity. In 5- to 10-year-old Pima Indian chUdren, a high fasting plasma insulin concentration (probably reflecting insulin resistance) predicted overweight 7-8 years later, especially in boys (Odeleye, de Courten, Pettitt, & Ravussin, 1997). Le Stunff and Bougneres (1994) reported that a hyperisulinemic response to meals is the earliest detectable abnormality in obese children, followed by the development of fasting hyperinsulinemia and insulin resistance. Although investigators are far from reaching a consensus in this area, these results seem to indicate that hyperinsulinemia, perhaps through the antilipolytic effect of insulin, m a y be an early risk factor for obesity. Despite the attractiveness of prevention strategies aimed at children, which could be based on correcting some of these early risk factors for obesity, caution should be exercised. Until w e fully comprehend the interplay a m o n g variability of energy metabolism, growth, and obesity, w e must be concerned about the risk of unforeseen adverse consequences, particularly in respect to interruption of normal growth pattern in early childhood and distorted body image, excessive dieting, and anorexia nervosa in adolescence. Additional information on child obesity is prpvided by Berkowitz and Stunkard and by Goldfield, Raynor, and Epstein in Chapters 25 and 26 of this volume, respectively.
METABOLIC ADAPTATION Studies in adult Pima Indians have allowed us to identify metabolic risk factors for body weight gain, such as a relatively low metabolic rate and low rate of spontaneous physical activity, a high respiratory quotient, and insulin sensitivity. W e have also observed that after weight gain the original abnormal state becomes normalized, and because the change in metabolic risk factors is greater than the cross-sectional data would predict, this m a y be a mechanism to counteract further weight gain (Figure 3.4). Changes in metabolic factors, which are not explained by changes in body weight and composition, are the hallmarks of metabolic adaptation. The concept of metabolic adaptation was introduced by the pioneering work of Keys and colleagues, w h o defined the drop in energy expenditure observed in healthy m e n in response to semistarvation "a useful adjustment to altered circumstances" (Keys, Brozek, Henschel, Mickelsen, & Taylor, 1950). A more recent definition of adaptation has been proposed in a report by several U.N. agencies (Food and Argriculture Organization, World Health Organization, & United Nations Uni-
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versity, 1985) as "a process by which a n e w or different steady state is reached in response to a change or difference in the intake of food and nutrients." Results from most overfeeding studies indicate that short-term experimental weight gain is accompanied by an overcompensatory increase in energy expenditure (Norgan &c Durnin, 1980; Sims et al., 1973; Tremblay, Despres, Theriault, Fournier, & Bouchard, 1992). A recent study indicates that most of the overcompensatory response m a y be due to an increase in nonexercise activity thermogenesis (Levine et al., 1999). SimUarly, most underfeeding studies reveal that in the short term, intentional weight loss leads to a decrease in energy expenditure beyond predicted values (Elliot, Goldberg, Kuehl, & Bennett, 1989; Heska, Yang, W a n d , Burt, & Pi-Sunyer, 1990; Keys et al., 1950). Therefore, there is substantial evidence that metabolic adaptation occurs in response to large perturbations in body weight over a relatively short period of time, but it is u n k n o w n whether similar adaptive mechanisms also operate in response to long-term weight changes in free-living conditions. W e recently examined longitudinal changes in energy expenditure and respiratory quotient associated with spontaneous long-term weight change in Pima Indians (Weyer et al., 2000). Results indicated that metabolic adaptation does occur in response to spontaneous long-term weight change, but that the magnitude of the adaptive changes is small and the interindividual variability is large. Based on these and other data, w e have developed a theoretical model to explain h o w metabolic propensity to obesity (or resistance to weight loss) m a y thus depend not only on initial rates of energy expenditure and fat oxidation, but also on h o w these measures change in response to weight change (Figure 3.6).
c .2 ra
a o •a o>
c "S 0) 2 Q. -o 115 >« fl) jz
metabolic drive t o w a r d s :
>• 2 weiglnt loss
i_ I« (0
c 4S u 0) . >
w e i g h t gain b o d y size
FIGURE 3.6. Based on our cross-sectional, prospective, and longitudinal studies in Pima Indians, we have developed a theoretical model to explain the possible role of energy metabolism in the long-term regulation of body weight. Cross-sectionally, energy expenditure and the ratio of fat to carbohydrate oxidation increase with increasing body size (prediction line), but at any given body size, both measures vary considerably among individuals. Prospectively, relatively low rates of energy expenditure or fat oxidation predispose to weight gain. In longitudinal analyses, a relatively low rate of energy expenditure or fat oxidation tends to normalize, but again there is large variability in this response among individuals. Thus the metabolic drive to weight gain m a y soon diminish in some individuals (limited weight gain, arrow lA), whereas it m a y be more sustained in others (larger weight gain, arrow IB). Opposite considerations apply to weight loss (arrows 2 A and 2B).
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LESSONS FROM ANIAAAL MODELS The study of obesity in human subjects is inherently difficult. This is due to factors related to obesity hself, including heterogeneity, age-dependent penetrance, and uncontrollable gene-environment and gene-gene interactions. In addition, ethical considerations prevent the use of m a n y invasive techniques in humans—for example, the measurement of gene expression in the hypothalamus. The use of animal models in the study of h u m a n diseases confers considerable experimental advantages for the dissection of heterogeneous and polygenic traits such as obesity. Elucidation of genes causing obesity in animal models has provided considerable insight into the molecular mechanisms regulating physiological processes such as energy balance. S o m e of the recent advances in our understanding of the regulation of energy balance, which have stemmed from work in animal models, are discussed below. It is likely that further gene discoveries in animal models will add to this knowledge and continue to identify pathways that are important in nutrient partitioning and energy balance in humans. (For a fuller discussion of this topic in general, see Chua & Leibel, Chapter 2, this volume.) In 1994, the genetic mutation that causes massive obesity in ob/ob mice was described (Zhang et al., 1994). The gene encodes an adipocyte-derived hormone k n o w n as leptin, which acts primarily on the hypothalamus as a "lipostat," thus tending to adjust the size of the body's energy stores. In mice homozygous for the ob mutation, a genetic alteration results in a complete absence of circulating leptin; these animals develop severe, early-onset obesity, with m a n y associated metabolic and hormonal abnormalities (including hyperphagia, defective thermogenesis, infertility, and Type 2 diabetes). These metabolic abnormalities are rapidly corrected by leptin administration, which causes significant reductions in food intake and increased energy expenditure, resulting in weight loss after only a few days of leptin administration (Campfield, Smith, Guisez, Devos, & Burn, 1995). The h u m a n gene encoding leptin has been screened in a large number of obese subjects, and only two families have been shown to have mutations resulting in leptin deficiency (Montague et al., 1997; Strobel, Issad, Camoin, Ozata, & Strosberg, 1998). Interestingly, humans with the leptin gene mutation have hyperphagia and defective sexual maturation, but their energy expenditure and glucose metabolism seem to be normal. In accordance with the parabiosis experiments of the 1970s (Coleman, 1973), the mouse db mutation was shown to be a genetic defect in the leptin receptor gene (Tartagha et al., 1995). Animals homozygous for this mutation, which exhibit a phenotype virtually identical to that of ob/ob mice, have elevated plasma leptin concentrations, similar to the majority of obese humans (Considine et al., 1996; Maffei et al., 1995). Analysis of the leptin receptor gene in humans has shown a number of polymorphic sites, some of which appear to be associated with body composition (Thompson, Ravussin, Bennett, & Bogardus, 1997). In one h u m a n pedigree, individuals homozygous for a leptin receptor mutation exhibited severe, early-onset obesity similar to that seen in db/db mice (Clement et al., 1998). Although the discovery of leptin and its receptor m a y uhimately facilitate the development of n e w obesity treatments acting through this pathway, clinical trials in humans have indicated that only some obese individuals m a y be sensitive to the weight loss effect of exogenous leptin administration (Heymsfield et al., 1999). In addition to the leptin pathway, studies in other animal models of obesity have also led to the discovery of other factors involved in the regulation of energy balance. Yellow agouti (Ay) mice were found to overexpress a protein, k n o w n as agouti, in the central nervous system (MUler et al., 1993). These animals exhibh a phenotype consisting of obesity, insulin resistance, infertility, and increased tumor susceptibility (Silvers, 1997). Subsequent studies found that agouti causes obesity by antagonizing the actions of a-melanocyte-
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stimulating hormone (a-MSH) at the hypothalamic MC4R (Gantz et al., 1993). In addition, MC4R-knockout mice exhibit an obesity phenotype similar to that observed in A ^ mice (Huszar et al., 1997). a - M S H is derived from the gene k n o w n as pro-opiomelanocortin ( P O M C ) , which was found to be linked with body fat content in Mexican Americans (Comuzzie et al., 1997), suggesting a possible role for this pathway in the pathophysiology of h u m a n obesity. In addition, two individuals with mutations in the P O M C gene were recently described with severe, early-onset obesity and bright red hair (Krude et al., 1998). Finally, several individuals from three different h u m a n pedigrees have been described to have a mutation of M C 4 R that is associated with hyperphagia and severe obesity (Hinney et al., 1999; Vaisse, Clement, Guy-Grant, & Froguel, 1998; Y e o et al., 1998). At least three other hypothalamic peptides have been discovered recently in animal models of obesity, which m a y be important in energy balance. Melanin-concentrating horm o n e ( M C H ) , discovered by differential display studies in ob/ob mice, is overexpressed in some animal models of obesity, and administration of M C H increased food intake in rats (Qu et al., 1996). A recent study suggests that M C H m a y act as a functional antagonist of the melanocortin pathway described above (Ludwig et al., 1998). Orexins A and B are recently described hypothalamic peptides that stimulate food consumption in rats (Sakurai et al., 1998). However, recent data suggest that orexins have more to do with arousal than with eating behavior (Lin et al., 1999). Another hypothalamic peptide k n o w n as cocaineand amphetamine-related transcript ( C A R T ) was recently discovered by differential display studies in animal models (Douglass, McKinzie, & Couceyro, 1995). Administration of C A R T to rats inhibited both basal and starvation-induced feeding (Kristensen et al., 1998). Further investigation of these and other hypothalamic peptides is likely to add to our understanding of the central regulation of energy balance in humans. Other studies in animal models have increased our knowledge of the role of certain genes in energy balance. For example, the recently discovered uncoupling proteins U C P 2 and U C P 3 have been suggested to play a role in energy balance in rodents, and studies are currently underway to investigate the role of these proteins in humans. Studies in our laboratory suggest that genetic variation at U C P 2 - U C P 3 is associated with metabolic rate in Pima Indians (Schrauwen et al., 1999; Walder et al., 1998). In summary, recent studies in animal models have contributed greatly to our understanding of the regulation of energy balance. N e w peptides and pathways have been discovered that could potentially lead to n e w therapies for the treatment of h u m a n obesity.
FUTURE DIRECTIONS Our studies on the regulation of energy expenditure in humans have provided evidence that approximately 3 0 % of the interindividual variability of body weight can be attributable to familial traits such as daily energy expenditure ( 1 0 % - 1 5 % ) , respiratory quotient ( 5 % ) , and spontaneous physical activity (10%). With the knowledge that up to 7 0 % of the variance in B M I is genetically determined, one has to conclude that a large proportion of the variance in B M I m a y be due to the effect of genes on factors not measured in our studies—that is, eating behavior and habitual physical activity in free-living conditions (Figure 3.7). In contrast to animal models, however, it has been very difficult to study the molecular mechanisms and resulting behaviors that underlie excessive energy intake in humans. Nevertheless, the identification of severe hyperphagia in individuals with mutations of the leptin, leptin receptor, and M C 4 R genes leaves little doubt that energy intake is as highly regulated at the molecular levels in humans as it is in animals. Furthermore, based on the results that have emerged from the recent use of n e w techniques such as positron emission tomog-
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FIGURE 3.7. Studies in monozygotic twins reared apart suggest that approximately 7 0 % of the variability in B M I is attributable to genetic factors and 3 0 % to the environment. Based in part on results horn our longitudinal studies in Pima Indians, we submit that the contribution of genetic factors controlling metabolic rate, respiratory quotient,fidgeting,daily physical activity, and hyperphagia to BMI variability can be estimated. From Ravussin and Bogardus (2000).
raphy and functional magnetic resonance imaging (fMRI), it seems likely that the level of complexity of the neuroanatomical correlates of eating behavior in h u m a n s could be m u c h higher than it is in rodents. W e have recently s h o w n that in response to a single meal, neuronal activity increases in the prefrontal cortex and decreases in the hypothalamus, thalamus, insular cortex, orbitofrontal cortex, and hippocampal formation in the brains of healthy m e n (Tataranni et al., 1999). A n inhibition of neuronal activity in the hypothalamic region following a meal w a s confirmed in a second study using f M R I (Matsuda et al., 1999). M o s t importantly, preliminary data suggest that brain responses to a meal m a y be substantially different between lean and obese subjects (Gautier et al., 2000). Such techniques applied to formerly obese subjects, as well as subjects suffering from eating disorders, m a y help identify the neurological pathways responsible for hyperphagia and obesity. Past difficulties in measuring habitual physical activity in humans have largely been alleviated by the advent of the doubly labeled water technique. Thus in the near future, it should be possible to better understand the interaction between the energy expended in daily physical activities and the development of obesity in children and adults. A greater knowledge of the physiology of obesity will ultimately c o m e from the current efforts to isolate all the genes related to weight gain. Over the past few years, genetic linkage studies have increasingly focused on complex traits such as obesity. Genome-wide scans have been completed in Mexican Americans (Comuzzie et al., 1997), in Pima Indians (Hanson, E h m , & Pettitt, 1998; N o r m a n et al., 1998), in a diverse population of European and African Americans (Lee et al., 1999), in French Canadian families (Chagnon, Perusse, Weisnagel, Rankinen, & Bouchard, 2000), and in French famUies (Hager et al., 1998). F r o m all these studies, major loci linked to obesity have been found on chromosomes 2, 5, 10, 11, and 20. Those areas of the genome are currently under intense investigation as they m a y lead to the cloning of obesity susceptibility genes. Although m a n y of us would like to think that obesity is a disease with multiple genetic/molecular explanations, a n e w paradigm m a y emerge from such research indicating that obesity results from "normal physiological variability within a pathoenvhonment." The corollary of this is that the pathology does not lie within the individual, but within
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the environment (HiU & Peters, 1998). Therefore, detailed research must be conducted to uncover the major environmental determinants of obesity—and, most importantly, to understand which are realistically modifiable. Historically, epidemics have been controlled only by including the environmental factors behind them in the resolution paradigms and ensuing public health actions. Examples of disorders and problems to which these strategies have been apphed include infectious diseases (drainage of s w a m p s for malaria control; infection control policies in hospitals); road crashes (median barriers and speed policing); smoking (taxation and smoke-free legislation); and heart disease (labels indicating saturated fat content of manufactured food; payment to dairy and meat producers based on protein, not fat, content). Although these examples m a y not translate directly to the problem of body weight regulation, the obesity epidemic needs a similar environmental solution to complement the current educational, behavioral, genetic, pharmacological, and surgical approaches. In the long run, the goal remains the s a m e — t o treat the individuals w h o are currently obese, and to prevent obesity in those w h o are still lean. Although the strategies for individual treatment and population prevention m a y be very different, both are d o o m e d if our understanding of the genetic and environmental causes of the disease is inadequate. It is this knowledge that will allow the flow of paradigms upon which clinicians and public health practitioners can base their programs and actions. Given the limited success of available treatments and the total failure of public health programs, n e w approaches to the solution of the problem of obesity are needed.
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E., Mohammed, S. N., Hurst, J. A., Cheetham, C. H., Eadey, A. R., Barnett, A. H., Prins, J. B., &c O'Rahilly, S. (1997). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature, 387, 903-908. Must, A., Spadano, J., Coakley, E. H., Field, A. E., Colditz, G., ^ Dietz, W . H. (1999). The disease burden associated with overweight and obesity. Journal of the American Medical Association, 282, 1523-1529. Norgan, N . G., Sc Durnin, J. V. G. A. (1980). The effect of 6 weeks of overfeeding on the body weight, body composition, and energy metabolism in young men. American Journal of Clinical Nutrition, 33, 978-988. Norman, R., Tataranni, P. A., Pratiey, R. E., Thompson, D. B., Hanson, R. L., Prochazka, M., Baier, L., Ehm, M . G., Sakul, H., Foroud, T., Garvey, W . T., Burney, D., Knowler, W . C , Bennett, P. H., Bogardus, C , Si. Ravussin, E. (1998). Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians. American Journal of H u m a n Genetics, 62, 659-668. Odeleye, O. E., de Courten, M., Pettitt, D. J., Si. Ravussin, E. (1997). Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children. Diabetes, 46, 1341-1345. Pittet, P. H., Chappuis, P. H., Acheson, K., de Techtermann, F., Sc Jequier, E. (1976). Thermic effect of glucose in obese subjects studied by direct and indirect calorimetry. British Journal of Nutrition, 35, 281-292. Poehlman, E. T., Melby, C. L., Si Bradylak, S. J. (1988). Resting metabolic rate and postprandial thermogenesis in highly trained and untrained males. American Journal of Clinical Nutrition, 47, 793-798. Prentice, A. M., Black, A. E., Coward, W . A., Si Cole, T. J. (1996). Energy expenditure in overweight and obese adults in affluent societies: A n analysis of 319 doubly-labeled water measurements. European Journal of Clinical Nutrition, 50, 93-97. Prentice, A. M., Black, A. E., Coward, W . A., Davies, H. L., Goldberg, G. R., Murgatroyd, P. R., Ashford, J., Sawyer, M., Sc Whitehead, R. G. (1986). High levels of energy expenditure in obese women. British Medical Journal, 292, 983-987. Prentice, A. M., 8c Jebb, S. A. (1995). Obesity in Britain: Gluttony or sloth? British Medical Journal, 311,437-439. Qu, D., Ludwig, D. S., Gammeltoft, S., Piper, M., PeUeymounter, M . A., CuUen, M . J., Mathes, W . F., Przypek, J., Kanarek, R., Sc Maratos-Flier, E. (1996). A role for melanin-concentrating hormone in the central regulation of feeding behavior. Nature, 380, 243-247. Ravussin, E. (1995). Obesity in Britain: Rising trend may be due to "pathoenvironment" [Letter to the editor]. British Medical Journal, 311, 1569. Ravussin, E., Acheson, K. J., Vernet, O., Danforth, E., Sc Jequier, E. (1985). Evidence that insulin resistance is responsible for the decreased thermic effect of glucose in human obesity. Journal of Clinical Investigation, 76, 1268-1273. Ravussin, E., Sc Bogardus, C. (2000). Energy balance and weight regulation: Genetics versus environment. British Journal of Nutrition, 83, 17-20. Ravussin, E., Bogardus, C , Schwartz, R. S., Robbins, D. C , Wolfe, R. R., Horton, E. S., Danforth, E., Sc Sims, E. A. (1983). Thermic effect of infused glucose and insulin in man: Decreased response with increased insulin resistance in obesity and non-insulin dependent diabetes mellitus. Journal of Clinical Investigation, 72, 893-902. Ravussin, E., Harper, I. T., Rising, R., Sc Bogardus, C. (1986). Energy expenditure by doubly labekd water: Validation in lean and obese subjects. American Journal of Physiology, 261, E402-E409. Ravussin, E., LiUioja, S., Anderson, T. E., Christin, L., Si Bogardus, C. (1986). Determinants of 24hour energy expenditure in man: Methods and results using a respiratory chamber. Journal of Clinical Investigation, 78, 1568-1578. Ravussin, E., LiUioja, S., Knowler, W . C , Christin, L., Freymond, D., Abbott, W . G., Boyce, V., Howard, B. V., Sc Bogardus, C. (1988). Reduced rate of energy expenditure as a risk factor for body weight gain. N e w England Journal of Medicine, 318, 467-472. Ravussin, E., Pratiey, R. E., Maffei, M., Wang, H., Friedman, J. M., Bennett, P. H., Sc Bogardus, C. (1997). Relatively low plasma leptin concentrations precede weight gain in Pima Indians. Nature Medicine, 3, 238-240.
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4
Genetics
a n d
B a c k g r o u n d , a n d
C o m m o n
Current Future
Obesities:
Status,
Strategies,
Prospects
R. ARLEN PRICE
W e are in a period of rapid growth in our knowledge about genetic influences on obesity. That growth is likely to reach unprecedented levels over the next few years and there are several reasons for this. Genes for several M e n d e U a n (single-gene) obesities have been identified and well characterized, resulting in the identification of key pathways that regulate energy intake, storage, and utilization. T h e H u m a n G e n o m e Project hasfinisheda draft D N A sequence (Lander et al., 2001; Venter et al., 2001). M a n y technological innovations, such as high throughput, automated sequencing, genotyping, mutation, expression screening, and functional analysis, developed as a part of or concurrently with the H u m a n Genome Project, are n o w generally available. In addition, the extremely large volume of data has stimulated the development of methods in bioinformatics needed for management and analysis. N e w methods of quantitative analyses for linkage disequilibrium and gene function have also been developed. Finally, several groups from around the world have developed large family cohorts, including extensive phenotypic and genotypic data. In spite of all this progress and promise, still very little is k n o w n about the specific genetic mechanisms that influence most h u m a n obesities. However, the tools at our disposal are powerful; the reagents and genetic data are extensive; and, not inconsequentially, w e have m u c h left to learn. It is difficult to imagine a more propitious time for studying the complex interplay of the multiple genes and environmental factors that influence c o m m o n forms of h u m a n obesity. Over 100 years' worth of scientific research has demonstrated that heredity plays a m a jor role in the development of body size and obesity (Price &c Lee, 2001; Price, Reed, & Guido, 2000). Surely plant and animal breeders have been aware of this relationship for much longer—at least since the domestication of multiple plant and animal species more than 10,000 years ago. However, it is only within the past few years, since the positional cloning of the mouse obese gene (Zhang et al., 1994), n a m e d the leptin gene, that w e have 73
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begun to understand the role of specific genes in the development of obesity. In the brief intervening period, the identification and characterization of several genes, particularly leptin, the leptin receptor, and agouti-related protein, have m a d e it possible to construct m a n y of the key pathways in the regulation of energy balance (described by C h u a & Leibel and by Tataranni & Ravussin in Chapters 2 and 3 of this volume, respectively). Perhaps because of the central importance of these regulatory mechanisms, mutations affecting the protein structures coded by these genes appear to occur only very rarely. After a worldwide search by m a n y investigators, few obese individuals have been found w h o carry major gene mutations: about 50 individuals with 19 mutations in 6 genes (Perusse, Rice, et al., 2001). Obviously, these mutations are too infrequent to m a k e any significant contribution to c o m m o n forms of obesity. The pattern of inheritance of obesity, combined with the absence of mutations in k n o w n major genes, suggests a complex m o d e of inheritance involving multiple genes. It is likely that m a n y genes have relatively small effects on obesity phenotypes, and expression almost certainly depends on both genetic background and environmental conditions. The complexity of the phenotype not only presents difficulties for finding the relevant genes, but also is likely to challenge our previous notions about h o w genetic variabihty influences phenotype. This chapter first reviews what w e k n o w about the inheritance of h u m a n obesity; it then discusses methodological obstacles, current status, strategies, and future prospects for identifying genes for c o m m o n obesities.
THE FAMILIAL/GENETIC I N H E R I T A N C E O F H U M A N
OBESITY
Human obesity has variously been attributed to inheritance and to individual character. Mild to moderate obesity clearly follows family lines and m a y more easily be accepted as beyond an individual's control. Extremely obese individuals, on the other hand, often stand out from other family members, and so their excess weight m a y more easily be attributable to character. Classical genetics has devised ways to explain such examples of heredity and variation. Genes passed from parents to children provide a basis for genetic inheritance, and gene segregation, the process by which only half of a parent's genes are passed on to each child, provides a mechanism for maintenance of genetic variation within families and populations. Differences in living conditions such as diet and exercise provide additional variation. It is clear from a number of family studies that obesity and thinness follow family lines (Grilo & Pogue-Geile, 1991; Maes, Neale, & Eaves, 1997; Price, 1987). Correlations a m o n g first-degree relatives (parents, offspring, siblings, and dizygotic twins) generally range from .20 to .30, suggesting a moderate heritabihty. Correlations are slightly higher within than between generations, suggesting the possibility of nonadditive or even nongenetic inheritance. O f course, the familial pattern alone is no guarantee of a genetic cause. FamUies share m a n y things besides genes, and at least some nongenetic assets are transmitted across generations. Because of practical and ethical limhations on h u m a n experimentation, researchers have depended on the natural experiments of twinning and adoption to separate nature from nurture in humans. F r o m the earliest reports, these studies have tended to support a genetic basis for obesity (Price, 1987). However, hmitations in study size and design left m a n y of the early reports open to different interpretations. During the 1960s and 1970s, it became fashionable to "debunk" biological explanations for behavioral traits, replacing them with envhonmental theories of sometimes questionable validity. W e find, for exam-
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pie, published statements such as the following: "Family line resemblances in fatness, however striking, m a y be less the product of genes held in c o m m o n than of the living-together effect" ( G a m , 1985). In fact, twin studies have found that identical twins are more highly correlated in body composition than are fraternal twins. Across multiple studies, correlations for adult m o n o zygotic twins generally range from .60 to .70, with values being generally higher and more variable in younger twins. Correlations for dizygotic twins are similar to those of other first-degree relatives. Adoption studies have found that adoptees resemble their biological relatives in body composition, but not members of their adoptive families. These and later studies demonstrated that obesity is highly heritable, and that at least for adults, family environment appears to have a negligible influence. Studies of twins reared apart (Price & Gottesman, 1991; Stunkard, Harris, Pederson, &c McClearn, 1990) have confirmed this pattern. Identical twins resemble each other to a similar degree, whether they are raised together or apart. O n balance, genes appear to account for as m u c h as two-thirds of individual differences in obesity in adults, with the remaining differences being due to idiosyncratic influences from outside the family. Obesity measures have also been analyzed as qualitative traits (e.g., obesity vs. normal weight). T h e "heritability" in this case is best reflected by a comparison of famUial and population affection rates, yielding an odds ratio or relative risk. Studies examining several obesity thresholds have found that the relative risk increases with more extreme obesity, from 1.5-3.0 for moderate obesity (90th percentUe for body mass index [BMI] greater than 30) to 3.0-9.0 for extreme obesity ( B M I greater than 40) (Lee, Reed, &C Price, 1997; Price & Lee, 2001). It is not clear whether it is appropriate to extrapolate from the absence of shared environmental influences on the normal range of body fat to these extreme levels. If family environmental factors were minimal, the results would suggest that extreme obesity is strongly influenced by genes. It will be fortunate if this interpretation is true, for a higher heritability should facilitate the identification of causative genes.
Gender Differences W o m e n have a higher percentage of body fat than m e n ; this increase in body fat for w o m e n is observed across m a n y countries and seems stable across cultures and dietary habits (Bray, 1994). Female children are fatter than male chUdren, so that behavioral differences between m e n and w o m e n (such as responsibility for food preparation) cannot account for gender difference in body fat (Forbes, 1972; Tanner, Hughes, &C Whitehouse, 1981). The specific biological mechanisms that account for this difference remain to be determined. Family studies have revealed n o general evidence for a pattern of transmission (e.g., X-linked d o m inant) that would explain the sex difference. A s reviewed in a later section of this chapter, three groups have reported suggestive X linkage to quantitative trait loci influencing mild obesity and fat distribution. However, the influence of these genes, if they prove to be real, is likely to be small. O n e obvious explanation for the increased adiposity of w o m e n relative to m e n is that autosomal obesity genes interact with the sex hormones to favor the accumulation of body fat in w o m e n . Although these sorts of interactions are speculative, influences in the reverse direction are clear. Adipose tissue provides a signal for sexual maturity in both mice and h u m a n s through the secretion of leptin (Chehab, 2000).
Population Differences Obesity is a disorder associated with the developed and developing world. Prosperity has produced m a n y changes in the environment, including less physical work; more leisure
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time; more sedentary forms of entertainment, especially television; and an increased availability of foods, especially those with high caloric content. Within the United States, obesity rates are highest in Native, African, and Hispanic Americans (Kuczmarski, Flegal, C a m p bell, & Johnson, 1994). U p to two-thirds of members of these groups are obese, as compared with about 3 0 % of non-Hispanic European Americans. S o m e of the highest rates of obesity occur in the Pima Indians of southern Arizona, where about rwo-thirds of adults in this group also have diabetes (Knowler et al., 1991). It is interesting that the increases in obesity and diabetes in the Pima closely parallel trends in acculturation during the past 50 years (Price, Charles, Pettitt, & Knowler, 1993). Obesity rates for Pima living in the Gila and Salt River areas of Arizona were apparently low early in the 20th century. A closely related Pima tribe that lives in Sonora, Mexico, and maintains a traditional lifestyle continues to have low obesity and diabetes rates today (Valencia et al., 1999), although the rates are stiU higher than in the neighboring Mexican population. The differences in diabetes and obesity rates in Native Americans as compared with European Americans prompted anthropologist James Neel (1962) to hypothesize that Native Americans and some other groups possess a "thrifty" genotype, which has allowed them to survive periods of feast and famine by increased efficiency in energy storage and expenditure. Although energy efficiency must have been an evolutionary advantage in more difficult and unpredictable times, this advantage m a y have become a liability in modern times of relative plenty. Although all h u m a n populations evolved in a changeable environment, some m a y have experienced more extreme fluctuations than others. The high rates of obesity in Pima Indians, other Native American groups, several Pacific Islander groups, African Americans, and Hispanic groups with Native American admixtures are consistent with this hypothesis. However, to date no specific "thrifty" gene or genotype has been identified, but some have been suggested. Both leptin (Spiegelman & Fher, 2001) and melanocortin 3 receptor ( M C 3 R ; Chen et al., 2000) genes have been reported to influence energy efficiency, although the mechanisms are u n k n o w n and the case for M C 3 R remains controversial.
T H E R O L E O F T H E E N V I R O N M E N T IN H U A A A N O B E S I T Y An intuitively compelling theory about the development of obesity is that it is due to patterns of diet and exercise that are learned in the home. This view has attractive features in that h provides a root cause, someone to blame, and a natural target for prevention. Some adoption studies do suggest that the family environment can influence level of obesity while children are living in the same h o m e with their parents (Bouchard, Savard, Despres, Tremblay, & Leblanc, 1985). However, these effects do not appear to be long-lasting and do not persist into adulthood. Other studies of child adoptees suggest that the effects are negligible even at an early age. Nonfamily environmental factors do influence obeshy. Although genetically identical individuals tend to be similar in levels of obesity and thinness, they are rarely identical. Studies of monozygotic twins demonstrate that although there is high concordance in the presence of obesity, there can be large differences in the extent of obesity for individuals having the same genotype (Price & Stunkard, 1989), especially w h e n the obesity in one or both twins is extreme. Presumably these discordances in level of obesity are due to differences in such factors as diet, exercise, and smoking that accumulate over a lifetime. Nonfamily environmental influences can be powerful. Cuhural changes appear to account for recent increases in the prevalence of obesity. The prevalence and extent of obesity in the United States have increased in more recent birth cohorts, especially a m o n g w o m e n (Kuczinarski et al., 1994). The rate of increase is striking, from a prevalence of about 2 5 %
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in 1980 to more than 30% in 1990. The increase has been particularly strong for Afric American women. Obesity also appears to be on the rise in European countries (James, 1995; S0rensen & Price, 1990). Most surveys have defined obesity as having a B M I greater than or equal to 27 kg/m^. In a more recent survey (Mokdad et al., 1999), a lower B M I value of 25 kg/m^ was used, resulting in an obesity prevalence of more than 5 0 % in the United States. It has become abnormal to be thin. W e may be sure that the genetic compositions of these populations have not changed substantially over the past 10-20 years, so the obesity increases must be due to culturally mediated change in diet and exercise. Although no direct links are possible, population data largely support this view. The obesity increases have closely paralleled increases in dietary fat (Fujimoto et al., 1995) and in sedentary activities such as watching television (Jeffery & French, 1998). Furthermore, several groups have experienced increases in obesity following exposure to Western culture and diet, for example, the Pima Indians (Price et al., 1993) and Pacific Islanders (Hodge et al., 1994). Genetic differences may mediate differential responses to cultural change through gene-environment interaction. Even following temporal increases, the heritability of obesity has remained substantial in all populations studied (Price, 1994). A n obvious question that comes to mind is whether genes may play a role in determining the response to a changing diet and pattern of exercise. That is, do genes influence who gains the most weight in our obesity-promoting environment? There is at least some experimental evidence that such gene-environment interactions can occur. For example, in one study all identical twins w h o were overfed for up to 3 months gained weight (Bouchard et al., 1990). However, there were large differences in the extent of weight gain, with identical twin pairs gaining similar amounts of body fat. Animal studies confirm this pattern of gene-environment interaction observed in humans. Genetically different strains of mice also vary in weight gain in response to high-fat diets (Fenton & Dowling, 1953; Schemmel, Mickelsen, & Gill, 1970; West, Goudey-Lefevre, York, & Truett, 1994; West, Waguespack, York, Goudey-Lefevre, & Price, 1994). Studies such as these demonstrate that genetic predisposition can determine the magnitude of a response to a nongenetic influence such as diet composition. As sedentary lifestyles and high-caloric diets become more common, any preexisting differences among individuals in genetic predispositions to obesity should be magnified through geneenvironment interactions. Gene-Gene Interactions in Obesity At least from animal studies, w e know that gene-gene interactions may also occur and may be quite common. For example, the extent of obesity and diabetes resulting from a single gene mutant depends on genomic background (Coleman & Hummel, 1975). Gene-gene interactions have been reported for several human disorders as well. Of particular interest is the possible interaction of the gene Calpain-10 with an unknown gene on chromosome 15 in the predisposition to Type 2 diabetes and possibly obesity (Cox et al., 1999; Horikawa et al., 2000). Although w e can only speculate at this point, the rich genetic diversity of human populations suggests that genetic interactions may be c o m m o n for complex disorders such as obesity.
METHODOLOGICAL ISSUES AND OBSTACLES Measuring Obesity Obesity is an end resuh of long-term energy imbalance, which can be due to high caloric intake, low energy expenditure, or abnormal partitioning of energy into storage as body fat
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(see Chapters 2 and 3 in this volume). Factors influencing the energy equation (stored energy = intake - expenditure) are numerous and are often difficult to quantify because of unreliability (e.g., food intake, macronutrient choices, and physical activity), expense (indirect calorimetry and thermic effect of food), or accessibility (nutrient partitioning). Genetic studies generally must focus on the cumulative summation of this equation over a period of m a n y years by measuring body composition through direct or indirect indices of the amount of body fat. The most accessible of these indices is B M I , a ratio of weight to height. Other c o m m o n indices are derived from total body water by electrical impedance and from relative body density by underwater weighing. The amount of subcutaneous fat m a y be quantified through measures of skinfolds at various anatomical sites. There are formulas for combining skinfolds into an estimate of total body fat, and a simple s u m works reasonably well. Direct imaging methods are also applicable, although limited by the expense of the procedures and the small size of most scanners relative to that of m a n y extremely obese people. Fortunately, these obesity measures are moderately correlated (.65-.85), and so the more accessible and inexpensive ones can be used in large-scale studies (Warden et al., 1996). Individual differences in body fat distribution or fat patterning, as opposed to overall amount of body fat, can also be measured through circumferences, skinfolds, and imaging. Several studies have demonstrated that fat distribution is largely uncorrelated with total body fat and is independently heritable (Borecki, Rice, Perusse, Bouchard, & Rao, 1994; Cardon, Carmelli, Fabsitz, & Reed, 1994; Hasstedt, Ramirez, Kuida, & W U U a m s , 1989; Rice, Bouchard, Perusse, & Rao, 1995; SeUers et al., 1994). Because of the relation of abdominal fat to cardiovascular disease, it is of more than academic interest to study the genetics of fat patterning in humans.
Instability of the Obesity Phenotype Obesity is an inherently changeable phenotype. Body weight fluctuates by 2%-3% during a normal day. M o s t people gain weight throughout m u c h of their lifetimes, and it has been shown that this propensity to gain weight is heritable (Bouchard et al., 1990). However, not aU obesity develops during adulthood. Between one-third and one-half of extremely obese people develop obesity in childhood or adolescence. Clearly, some overweight children eventually grow into lean adults; the more extreme the obesity, however, the better it tracks into adulthood. In addition, early-onset obesity has been reported to run in families, and to increase the risk that other relatives will be similarly obese (Price et al., 1990). The rates might simply appear higher because relatives with familial early-onset forms of obesity will tend to have more affected members in cross-sectional studies of individuals varying in age, even if censoring (an epidemiological control) is taken into account in a pooled sample. Lifetime rates estimated separately for early- and late-onset famUies could be simUar. Whether genetic differences affect level of obesity or only timing of its development, age of onset of obesity has been shown to be a herhable trait (Price et al., 2000). Identifying Genes for Common Obesities Perusse, Chagnon, and coUeagues (2001), in their annual summary of the status of the obesity gene m a p , report more than 250 genetic loci linked or associated with obesity. These include 10 major genes from animal models, 6 nonoverlapping major genes in humans, 24 genetic syndromes, 115 animal quantitative trait loci, 48 candidate genes with reported associations in humans, and 59 loci with at least one report of possible linkage. Even with
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these comprehensive annual updates, the volume of new work makes it impossible for any review to be completely current, and that is particularly true of a published volume like this one. Therefore, in this chapter only consistent patterns are reported. Included in the comprehensive Perusse and colleagues review are genes that have been well characterized, such as leptin and genetic loci that have only been inferred from genetic linkage studies. T h e strength of evidence for particular genes or genetic loci is quite variable, ranging from the identification and functional characterization of specific single-gene mutations to unreplicated reports of linkage and association. O n e obvious question at the outset is whether 250 or more genes could influence obesity. Based purely o n what w e have learned about the biological complexity, w e m a y confidently predict that at least this m a n y genes m a y be involved and probably more. However, if w e frame the question slightly differently and ask whether these particular 250-plus genes are the ones that account for individual h u m a n differences, w e would say with equal confidence that they almost surely include a number of false-positives, while the effects of m a n y other genes have yet to be detected. Finally, m a n y of the genes implicated through animal models are so important that they appear to be largely invariable, and thus have little influence on c o m m o n h u m a n obesity.
Multiple Testing for Multiple Genes Since other chapters in this volume deal with plausible biological candidate genes and regulatory pathways, this chapter briefly considers the technical reasons for very high falsepositive and false-negative rates and indicates h o w to distinguish the real or likely from the merely possible but unlikely. This technical discussion leads to a practical consideration of a few genomic regions for which there is emerging consensus. Identifying the genetic loci influencing a multigenic trait such as obesity depends on m a n y factors. If considered as a quantitative trait, power depends on the overall heritability and the proportion of trait variance due to a particular locus. For a qualitative dichotomization, power depends on the relative risk attributable to a locus. For a moderately heritable trait (approximately .40-.70), such as percentage of body fat or B M I , sample sizes that have been examined thus far could have expected to detect loci accounting for no less than about 1 5 % - 2 0 % of the total trait variance. For qualitative traits, current sample sizes have the power to identify a gene with an attributable risk of no less than 1.5-2.0. In the context of an overall risk of 3.0-9.0 for obesity, identifying one or a few genes seems feasible; again, however, this wiU only be possible if some of the loci account for a sizable portion of the observable variance. High rates of false-positive findings in genetic linkage and association studies are due to multiple testing in the extreme, basically to conducting a large number of tests of genes and markers over the entire h u m a n genome w h e n the prior probability of any one gene's involvement is low. Given the size of the h u m a n genome, about 3 billion base pairs, there is no w a y to avoid the problem of multiple testing. For qualitative traits with clear phenotypes and single-gene inherhance, a nominal odds ratio favoring linkage of 3.0, roughly equivalent to a nominal p value of .001, w a s chosen in order to give a genome-wide posterior probability level of about 5 % . For complex traits such as obesity, m u c h higher odds ratios are needed because there are multiple genes to identify and variable phenotype definitions muhiply the n u m b e r of tests, making the false-positive rate still higher. For association studies, the false-positives pose an even greater problem. T h e power to detect true associations is lower than for linkage, given equivalent sample sizes. It does not require any familiarity with genetics to k n o w that low power and a high error rate m a k e the
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worst possible combination. One methodological study (Carey & WUUamson, 1991) estimated that as m a n y as 8 0 % of replicated association studies m a y be false! It is a sobering point that is well to keep in mind. Several multipoint tests of association have been devised or are under development that appear to have greater power and m a y have lower error rates; however, they have not yet been applied in any systematic w a y to obesity phenotypes. Replication is the most obvious w a y around the false-positive problem, but repeating linkage and association results has its o w n difficulties. For a single-gene trait without heterogeneity, the sample size needed for replication should be the same as or less than the original. However, with a multigenic trait, the problem changes from finding at least one gene out of m a n y possibilities to finding exactly one gene previously identified. The difference is roughly analogous to the difference between finding any one of a number of needles in a haystack compared to finding exactly the same needle that was identified previously and then thrown back. A few years ago, Suarez, H a m p e , and V a n Eedewegh (1994) estimated that the time to replication (proportional to sample size) wiU at least double that of the initial sample. O n e conclusion for a multigenic trait such as obesity is that replication will be difficult and does not necessarily m e a n the original result is false. It is easy to see that a temptation to invoke this principle to explain inconsistent results is a prescription for scientific nihilism. For example, every geneticist could have his or her o w n gene with no expectation of replication. Obviously, this extreme view is scientifically unacceptable. O n the one hand, w e should not dismiss unreplicated studies. O n the other, w e must insist on independent replication before accepting any result as true. However difficult, replication is the only reasonably sure w a y to validate results from genetic studies.
Genome Scans for Obesity-Related Phenotypes A genome scan tests for linkage between a phenotype (e.g., obesity) and evenly spaced markers spanning the genome such that no gene should be more distant than 5 million base pahs from a marker. Typical scans for obesity used about 300 or more marker genotypes on 500 or more individuals for a m i n i m u m of 150,000 genotypes. A few scans used m a n y more. Results from thefirstnine scans are reviewed in this chapter with the understanding that data collection, data analysis, and publication are ongoing for some of these and other studies. In addition to full scans, there have been other linkage studies that focused on smaller regions of the genome. This chapter reviews only selected studies that have supported results from the nine full scans. Table 4.1 hsts the samples examined in the scans. All nine scans found at least nominally significant results for one or more obesity-related phenotypes. In fact, there were 45 nominally positive linkage results for 37 genomic regions. The large number and g e n o m k dispersion of the results is a bit bewildering; however, 11 of the regions were independently identified more than once and the largest number are concentrated in only three regions. O n e of the regions, chromosome 18q21, was only weakly supported, for percent body fat in the Quebec study and for a mild obesity phenotype in the Finnish study. The other two regions received strong support from at least one study and at least nominal support from others. The two regions, along with obesity phenotypes and supporting samples, are summarized in Table 4.2. The French group from Lille and Parisfirstreported linkage of obesity to chromosome region 10p21 at about 55 c M (centamorgans, on average about 1 mUlion base pairs per c M ) from the p (short arm) terminus (Hager, Dina, et al., 1998). Supporting studies followed from the Marburg (Hinney et al, 2000) and Philadelphia (Price, 2001) groups used comparable phenotypes. The Heritage Family Study found support for linkage to this re-
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TABLE 4.1. Samples Examined in the First Nine Obesity Genome Scans Pima Indians (Phoenix Study) (Hanson et al., 1998; Norman et al., 1997,1998; Walder, Hanson, Kobes, Knowler, Sc Ravussin, 2000) Mexican Americans (San Antonio Heart Study) (A. G. Comuzzie et al., 1997; Hixson et al., 1999; MitcheU et al., 1999) French famihes (Paris-Lille) (Hager, Dina, et af, 1998) European Americans and African Americans (Philadelphia) (Lee et al., 1999) European Americans (French Canadians, Quebec Family Study) (Perusse, Rice, et al, 2001) European Americans (Heritage Family Study) (Bouchard et al., 2000; Chagnon et al., 2001) Old Order Amish (Hsueh et al., 2001) European Americans (TOPS Study) (Kissebah et al, 2000) Finnish families (Ohman et al., 2000; Perola et al., 2001)
gion using s o m e w h a t different phenotypes and analytic methods, variance component analyses of B M I and fat mass. Finally, the scan of the Old Order Amish sample supported linkage to leptin adjusted for B M I , perhaps a measure of leptin resistance that is c o m m o n l y associated with obesity. G e n o m i c sequence for this region is scant and there are few k n o w n genes, none of which are obvious candidates. While the absence of candidates m a y m a k e it difficult to identify a specific gene in c h r o m o s o m e region 10p21, it also raises the possibility, and excitement, of finding something n e w and unexpected. T h e San Antonio group reported linkage of plasma leptin to markers in 2p21 at about 57 c M from the p terminus (A. G. Comuzzie et al., 1997). T h e same group has presented additional support using augmented data from the original sample. T w o other groups (one
T A B L E 4.2. Genomic Regions with Most Consistent Support for Linkage to Obesity Genomic region Phenotype Sample 10pl5-pl2 Obesity French German European American (Philadelphia) African American (PhUadelphia) BMI, fat mass European American (Heritage Family Study) Leptin/BMI Old Order Amish 2p21
BMI, F M , leptin
Mexican American (San Antonio Heart Study)
Leptin French African American (Chicago Study) European American (TOPS Study)
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completely independent) have presented supportive results. The French group reported a replication that was strong in terms of support for linkage as well as for the congruence of the genomic location (Hager, Dina, et al., 1998). Resuhs from separate African American samples analyzed by the San Antonio group also provide support for the 2p21 linkage, although the hnkage was m u c h weaker (Rotimi et al., 1999). This region centers on the genomic location of the gene for proopiomelanocortin ( P O M C ) , a precursor of melanocortins that interact with leptin. Although it is clear that P O M C plays an important regulatory role in leptinmelanocortin pathways, the evidence that P O M C gene variability accounts for linkage to the leptin phenotype is so far only circumstantial. N o specific variability in coding or regulatory regions has been found, and m a n y other genes lie within the linked interval. It is in any case an interesting coincidence. The Pima group reported linkage of several obesity-related phenotypes to markers in llq22-24. N o n e of the eight other scans have reported linkage to this region. M o r e wiU be said about this group later in the chapter. Finally, our group in Philadelphia reported hnkage of obesity to markers in 20ql3 at about 71-85 c M from the p terminus (Lee et al., 1999). The location is close to previously reported linkages from the Quebec sample (Lembertas et al., 1997). There was some support from analyses of female sibling pairs in the French group; however, there was no linkage in the overall sample (Hager, Dina, et al., 1998). The Pima study reported linkage to 24-hour respiratory quotient, but the location is well centromeric of the 20ql3 location (Norman et al., 1998). This region of the long arm of chromosome 2 0 is rich in k n o w n and orphan candidate genes, including the melacortin 3 receptor, C A A T enhancer binding protein beta, and a number of genes for D N A binding or signahng proteins. The region also includes genes for adenosine deaminase, agouti-signaling protein, and a gene for maturityonset diabetes of the young. However, the linked region spans about 4 0 miUion base pairs, extending approximately from protein tyrosine phosphatase 1 beta in 20qll-12 to melanocortin 3 receptor in 20ql3. Overall, the agreement of results across multiple groups, samples, analytic methods, and related phenotypes is encouraging. Obviously, there are also m a n y failures to replicate. The nonreplications m a y be explained in part by the relatively low sample sizes and correspondingly reduced power of all the studies. Particularly in the case of the Pima Indians, the differences in results m a y also be due in part to genetic heterogeneity a m o n g samples. Heterogeneity m a y also account, at least in part, for differences a m o n g seemingly similar samples of European Americans. If obesity is indeed caused by multiple genes with relatively small effects, random sampling theory would predict differences in the representation of particular genes across the various samples. Only the the French and Finnish groups have published results on a full scan of the X chromosome (Hager, Dina, et al., 1998; O h m a n et al., 2000), although the Philadelphia group has reported results at scientific meetings. In the original publication of the French scan, they reported a secondary linkage to X p 2 1 . The Finnish group found no linkage in X p , but a modest linkage resuh in Xq. The PhUadelphia group found hnkage to markers in X p 2 1 in two separate samples, one European American and one African American. However, the linkage results were for a measure of fat distribution and localized to a region several c M centromeric of those from the French sample. At the least, these ambiguous results support the need for other groups to examine the X chromosome.
Other Genomic Regions with Independent Support for Linkage Although not identified in the context of a full genome screen, one other genomic location has received support from multiple independent groups. Several groups have reported link-
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age to markers flanking the leptin gene in 7q31 (Clement et al., 1996; Duggirala et al., 1996; Reed et al., 1996). Although there have also been negative reports, a meta-analysis found that the aggregate results were highly significant (AUison & H e o , 1998). Moreover, several groups have found evidence of associations or hnkage disequihbrium between sequence variability 5' of the leptin gene and obesity phenotypes, particularly for extreme obesity (Hager, Clement, et al., 1998; Li et al., 1999; Roth et al., 1998). T h e accumulated resuhs suggest a gene of small effect, primarily on extreme obesity. It is still unclear whether the association is due to variation in the leptin promoter or some other nearby gene, since disequilibrium appears to extend over a large interval.
FUTURE STUDIES: H O W C A N W E IDENTIFY GENES FOR C O M M O N F O R M S O F H U M A N OBESITY? Additional Linkage Studies Linkage studies represent the best way of regionally mapping new genes or genes with unanticipated effects on obesity phenotypes. It is important that additional linkage studies be completed, but future studies should have larger sample sizes in order to increase power and facilitate replication of existing linkages. Larger size can be achieved either by augmenting existing samples or by pooling data; the latter approach provides the largest samples, but the former permits independent replications. Given the large number of studies, it seems best to publish the primary results independently. Additional separate analyses m a y be coordinated a m o n g groups through the selection of comparable subsamples, phenotypes, and analyses. In some cases it m a y be appropriate to pool more disparate data. However, the analytic adjustment needed to achieve standardization a m o n g samples m a y ultimately be self-defeating, since any necessary assumptions will undermine confidence in the results. Future linkage studies should also explore more complex models. For example, a genome scan of swine found that genomically imprinted genes are c o m m o n . Several groups have developed linkage methods that incorporate parent-of-origin effects that would be expected with imprinting. However, there have been no published reports applied to obesity. In collaboration with Christopher A m o s , w e have conducted preliminary analyses of obesity phenotypes on one h u m a n chromosome. W e found strong evidence for a maternal effect, but our results have not yet been published. Another consideration that m a y be incorporated into linkage analyses is gene-gene interaction. Such interactions are c o m m o n in animal models (Coleman & H u m m e l , 1975). M y laboratory has completed preliminary work on five regions of three chromosomes that have been reported to be linked to obesity phenotypes. W e found a strong interaction between t w o of the regions. T h e major difficulty with this approach that has not yet been solved is the familiar one of multiple testing. T h e scope of the problem is m u c h greater in this case because the number of tests of interactions could be as high as the number of tests from a genome scan squared. For a modest example, consider a scan with 350 markers and 5 phenotypes; the potential number of interactions is over 3 million! Using split samples and requiring multiple replications is one approach; however, the reduced error rates will come at a great cost to power. T h e difficulties should not preclude this approach, since many or even most of the gene effects in h u m a n obesity m a y depend on the interactions of particular genes with genomic background. W e cannot understand the genetics of c o m m o n obesity without developing solutions to these inherent difficulties. There are, however, limitations to linkage studies that will m a k e it difficult to locate genes once linkage has been established. First, the resolution of hnkage tends to be poor.
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with linked intervals extended over at least 2 million base pairs. Many genes extend over only a few tens of thousands of bases, and most over only a few thousand. Thus m a n y candidate genes m a y be contained in one linked region. A s if these complications were not enough, there are others as well. Coding regions of exons have very low variability. Noncoding regions have high variability, but most polymorphisms are probably neutral. Finally, gene locus and allelic heterogeneity, combined with possible interactions with background genotype, will m a k e it difficult to choose unambiguously a m o n g possible candidate sequences based on within-family segregation alone.
Association Studies and Linkage Disequilibrium Fine mapping is likely to require some variation of association methods. A genetic association is the co-occurrence of particular alleles at different loci above chance levels. Associations between particular alleles arise because mutations occur on specific haplotypes (contiguous D N A sequence on a single chromosome) or because equihbrium populations undergo bottlenecks or genetic drift (random selection of small samples during meiosis that does not permit representation of all alleles), thereby increasing the associations a m o n g alleles in the preserved haplotypes. H o w long these associations are maintained depends on recombination, which in turn depends on physical distance. Initial disequihbrium for unlinked loci is decreased by half in each generation, for example, by more than 9 9 . 9 % within 10 generations, a little over two centuries. By comparison, 7,000 generations (about 140,000 years) are required to reduce an association between tightly linked loci (about 100 kilobases [kb]) by the same amount. This simple example assumes steady states that have not existed in h u m a n populations and the absence of selection pressures favoring nonrecombinants, but the basic principle appears to hold. Jorde (1995), for example, has shown that over distances of 100-500 kb, physical distance is well estimated by disequUibrium, although the relationship breaks d o w n at distances shorter than about 60 kb (Jorde et al., 1994). Kruglyak (1999) has suggested that disequilibrium might only extend over much shorter distances of 3-30 kb. However, this estimate assumes a uniform distribution of disequihbrium over the genome. Empirical data (Clark et al., 1998; Jorde, 1995; Jorde et al., 1994; Li et al., 1999) suggests a more complex view, with marker-marker allelic disequilibrium extending over more than 500 kb in some locations, but not existing at all over intervals of a few hundred base pairs within the same region. A more recent investigation of linkage disequilibrium in the h u m a n genome found that the median distance for detection is about 30 kb (Reich et al., 2001). However, there was extreme variability. The extended range of disequilibrium in m a n y cases will facilitate fine mapping of a gene. However, the discontinuities will require dense m a p s to assure detection and will m a k e gene identification difficult. It m a y also be necessary to locate genomic regions in disequUibrium with obesity phenotypes using samples drawn from relatively young populations, for example, groups reproductively isolated from others for 6-10 generations. Samples from older populations, especially Africans, m a y be needed for fine disequilibrium mapping.
SPECIAL P O P U L A T I O N S Genetically distinct groups may differ from others in the patterns of linkage and association with particular obesity phenotypes. For example, the Pima sample is unique in several respects that m a y m a k e replication of the llq23-24 linkage findings difficuh. A s mentioned earlier in this chapter, the only other Pima group (from Sonora, Mexico) live in a geograph-
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ically isolated area, maintain tradhional diet and customs, and, most important, do not tend to be obese. If there is a "thrifty genotype," one might expect all or most Pima to have it, since only changes in diet and exercise were necessary to produce extreme obesity in their northern relatives. O n e approach that has not been fully utilized with the Pima is to focus on genetic differences between Pima and other groups. M o s t genetic studies, including the genome scans, have focused on genetic differences within the population. It is clear that obesity is negatively correlated w h h the proportion of non-Pima admixture (Williams, Long, Hanson, Sievers, S>C Knowler, 2000). With currently available chip technologies, it m a y be possible to systematically examine differences in gene frequencies and gene expression between Pima and other groups. These are population-based studies that are discussed in the next section.
Population-Based Association Methods: High P o w e r a n d High Error Rates The most common method of estimating association in human populations, and one of the most frequently applied to obesity phenotypes, is an epidemiologic standard: the comparison of cases and controls. In its simplest form, this method involves making comparisons of allele or haplotype frequencies between affected individuals and controls matched by various means. This approach is very powerful and has been crucial in identifying the role of genes in a number of complex traits, particularly autoimmune diseases associated with the major histocompatibility complex, for example, insulin-dependent diabetes mellitus (Hitm a n et aL, 1985). Association methods are extremely sensitive to stratification and have had mixed success w h e n applied to c o m m o n traits in admixed populations. Association studies of obesity have been summarized by Perusse, Chagnon, and coUeagues (2001), and, for most, there are as m a n y or m o r e negative reports as positive ones. In part, this inconsistency m a y be due to the greater difficulty in replicating a positive finding for a multigenic trait (exactly one allele of one particular gene) than in finding an initial positive result (at least one allele of any gene) (Suarez et al., 1994). S o m e of these associations m a y be true positives awaiting confirmation with an appropriate sample, but m a n y are likely to be false. The difficulty in distinguishing truth from falsehood is demonstrated by reports of associations with the Trp64Arg polymorphism in the beta-3-adrenergic receptor. Allison, H e o , Faith, and PietrobeUi (1998) performed a meta-analysis of 23 studies and concluded that the overall pattern of results is not significant. However, soon after the publication of their study, a n e w metaanalysis found support for an association (Fujisawa, Ikegami, Kawaguchi, & Ogihara, 1998). Actually, the p values for both studies were near .05, but the conclusions were contradictory. In spite of this mixed history, there is an important place for case-control samples in studies of complex traits. Khoury and Y a n g (1998) have reviewed characteristics of case-control designs and m a d e a compelling argument for their continued use in genetic studies. They give a n u m b e r of reasons, including their relative ease compared w h h family studies, their equal or greater power in most circumstances, their ability to estimate relative risk and fraction of a disease due to particular alleles, and the ability to assess gene-gene and gene-environment interactions. There have been several attempts to minimize one of the major weaknesses of population-based studies, namely, stratification, by matching samples for genomic background. Automated technologies permit the luxury of using 50 or more marker loci (unlinked to the phenotype of interest) for matching purposes or for tests of heterogeneity. Although the val-
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ue and potential pitfalls of genomic matching need to be established in practice, the high power of population studies appear to m a k e them ideal for screening. Truth or falsehood of positive results can be established through replication or through more conservative familybased methods.
Family-Based Association Methods: Less Prone to Error Family-based association methods were developed as an alternative to case-control studies. The basic idea was to avoid problems associated with population structure by substituting untransmitted parental alleles or haplotypes in place of unrelated controls. These methods differ from other tests of linkage, in that the focus of the analysis is on allele or haplotype sharing across families rather than on identity by descent within families.
Why Particularly High Levels of Statistical Significance Are Required for Association Studies Linkage results between markers and a trait tend to be highly correlated when the markers are located very close together in the same chromosome region. This phenomenon occurs because large portions of chromosomes are passed on un-recombined, and any group of siblings will tend to share large chromosome segments identical by descent. However, linkage disequilibrium is due to the lack of recombination over large numbers of generations, and normally extends over very small regions of 200 kb or less in outbred populations (Lander & Schork, 1994). The median distance is only about 30 kb, but different genomic regions are extremely variable (Reich et al., 2001). For this reason, disequilibrium results usually will not be correlated for closely linked markers, and it will be necessary to apply a correction for multiple testing for each allele of each locus tested. Genome-wide significance levels of 10"' (Risch & Merikangas, 1996) or less (Kruglyak, 1999) m a y be needed to reach empirical significance of even 5 % . Without appropriate analyses and controls, 1 in a biUion p value, which most researchers have seen only while asleep, m a y be no better than 1 in 20, a value they are well used to seeing while awake. Although it is possible to minimize the problem of multiple alleles by focusing on biallelic single-nucleotide polymorphisms, or by employing maximum-likelihood methods (CoUins &c Morton, 1998; TerwiUiger, 1995), the problem of testing multiple loci in whole genome association scans remains a big one. One w a y of reducing the scope of the problem using currently available methods is to do "gene scans" rather than genome scans; although it m a y not always be possible to identify sufficient numbers of polymorphic genetic markers within or near all genes of interest. In a study of 9.7 kb of the lipoprotein lipase (LPL) gene, 88 polymorphisms were detected (Clark et al., 1998; Nickerson et al., 1998). This rate is higher than previously supposed. O u r o w n studies of the 5' region flanking the leptin gene found 16 polymorphisms (all biallelic) in 3 kb—less than the rate found for the L P L gene, but still m u c h higher than expected (Li et al., 1999). Although m a n y individual sites have limited frequency, variable sites m a y occur on average every 500 base pahs of D N A sequences (Nickerson et al., 1998). In the published studies of the L P L gene and in our investigations of the leptin gene, m a n y of the polymorphisms appear to be extremely old, most likely predating the spread of modern humans out of Africa and running m u c h deeper into h u m a n evolutionary history. For example, in the report by Clark and colleagues (1998), one allele of each polymorphism was found in chimpanzees, making the polymorphisms somewhere between 100,000 and 4.5 million years old. T h e n rough estimate for the two "clades" (roughly meaning "root" or "branch") identified in theh haplotype analysis was 1.2 m U h o n years, and most observed polymorphisms are probably more recent.
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This work raises several issues for mapping complex traits through linkage disequilibrium. Over distances of even a few tens of thousands of bases, the number of haplotypes segregating in an outbred population wUl approach the number of chromosomes. Over largeenough distances, all chromosomes are likely to be unique. Although this latter statement seems self-evident, the scale of haplotype diversity was not apparent until recently. Another difficulty presented by these findings is that disequilibrium is highly variable across the genome (Reich et al., 2001) and m a y extend over distances of only a few thousand bases in some regions (Kruglyak, 1999), making linkage-disequilibrium-based genome scans difficult if not impractical, at least with current technology. Yet another complication is that over small distances the extent of disequilibrium will be variable and can be discontinuous, making it difficult to identify sequence variability accounting for a phenotype association or linkage without some other insight into the nature of the particular sequences examined, for example, through information about population history. Clark and colleagues (1998) reported that the observed haplotypes showed considerable population structure. W e also found differences between European and African Americans in our studies of the leptin gene. However, the Clark study found some population overlap in regions as small as 1-2 kb. O n the other hand, they also noted the existence of two clades that extended over m u c h of the 9.7-kb region. They drew the intriguing conclusion that there m a y be functional significance in patterns of non-protein-coding variation over large distances. Their conclusion is very speculative, but their results suggest the equivalent of D N A sequence interactions for patterns of variability in flanking and intronic regions of genes. It is well k n o w n that D N A , R N A , and amino acid sequence variability can affect transcription, processing, and protein folding, respectively. However, the nature of these longdistance interactions is as yet u n k n o w n . Although the extent of sequence variability is only beginning to emerge, it is apparent that it will be important to study the pattern of disequihbrium a m o n g multiple markers in any given region, in order to select haplotypes for studies of associations with complex phenotypes. These sequence polymorphisms m a y replace structural gene mutations in what w e c o m e to understand as "genes" for complex traits such as obesity.
CONCLUSION Over the next few years, it should be possible to identify DNA sequence variability associated with c o m m o n forms of obesity. However, larger-scale linkage studies and linkage disequilibrium studies will be needed. M u c h genetic variability is of ancient origin and probably existed before m o d e r n h u m a n groups left Africa 40,000-100,000 years ago. A n intriguing hypothesis is that m u c h of the sequence variability related to obesity evolved under selective pressure to promote metabolic efficiency and energy storage, leading to epidemic obesity in the presence of m o d e r n living condhions. W e m a y need to reconsider the suggestion of James Neel (1962) regarding "thrifty genes" in some indigenous populations. It n o w appears that all existing populations are the closely related descendents of a few thousand modern humans. Thus, w e must all carry a collection of ancient thrifty genes.
ACKNOWLEDGMENT
The preparation of this chapter was supported in part by National Institutes of Health Grants No. R01DK44073, N o . R01DK48095, and N o . R01DK56210 to R. Arkn Price. The review of linkage studies drew not only on the published literature cited in the references, but also on discussions with
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participants of the NIDDK-sponsored ADI-MAP working group in July and August 2001. Special thanks to David Allison, Tony Comuzzie, and Louis Perusse in particular and to Sue Yanowski and others at N I D D K forfinancialand intellectual support.
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Lehrach, H., Reinhardt, R., McCombk, W. R., de la Bastide, M., Dedhia, N., Blocker, H., Hornischer, K., Nordsiek, G., Agarwala, R., Aravind, L., BaUey, J. A., Bateman, A., Batzoglou, S., Bhney, E., Bork, P., Brown, D. G., Gurge, C. B., Cerutti, L., Chen, H. C , Church, D., Clamp, M., Copley, R. R., Doerks, T., Eddy, S. R., Eichler, E. E., Furey, T. S., Galagan, J., GUbert, J. G., Harmon, C, Hayashizaki, Y., Haussler, D., Hermjakob, H., Hokamp, K., Jang, W., Johnson, L. S., Jones, T. A., Kasif, S., Kaspryzk, A., Kennedy, S., Kent, W . J., Kitts, P., Koonin, E. V., Korf, I., Kulp, D., Lancet, D., Lowe, T. M., McLysaght, A., Mikkelsen, T., Moran, J. V., Mulder, N., Pollara, V. J., Pouting, C. P., Schuler, G., Schultz, J., Slater, G., Smh, A. F., Stupka, E., Szustakowski, J., Thierry-Mieg, D, Thierry-Mieg, J., Wagner, L., WaUis, J., Wheeler, R., W U U a m s , A., Wolf, Y. I., Wolfe, K. H., Yang, S. P., Yeh, R. F., Collins, F., Guyer, M . S., Peterson J., Felsenfeld, A., Wetterstrand, K. A., Patrinos, A., Morgan, M . J., Sc Szustakowki, J. (2001). Initial sequencing and analysis of the human genome. Nature, 409(6811), 860-921. Lander, E. S., & Schork, N . J. (1994). Genetk dissection of complex traits. Science, 265, 2037-2048. Lee, J. H., Reed, D. R., Li, W-D., Xu, W., Joo, E-J., Kilker, R. L., Nanthakumar, E., North, M., Sakul, H., Bell, C , & Price, R. A. (1999). Genome scan for human obesity and linkage to markers in 20ql3. American Journal of H u m a n Genetics, 64(1), 196-209. Lee, J. H., Reed, D. R., Sc Price, R. A. (1997). Familial risk ratios for extreme obesity: implications for mapping human obesity genes. International Journal of Obesity Related Metabolic Disorders, 21, 935-940. Lembertas, A. V., Perusse, L., Chagnon, Y. C , Fisler, J. S., Warden, C. H., PurceU-Huynh, D. A., Dionne, F. T., Gagnon, J., Nadeau, A., Lusis, A. J., & Bouchard, C. (1997). Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. Journal of Clinical Investigation, 100, 1240-1247. Li, W., Reed, D., Lee, J., Xu, W., Kilker, R., Sodam, B., Sc Price, R. (1999). Sequence variants in the 5'flankingregion of the leptin gene are associated with obesity in women. Annals of H u m a n Genetics, 63, 227-234. Maes, H. H., Neale, M . C , & Eaves, L. J. (1997). Genetic and environmental factors in relative body weight and human adiposity. Behavioral Genetics, 27(4), 325-51. MitcheU, B. D., Cole, S. A., Comuzzie, A. G., Almasy, L., Blangero, J., MacCluer, J. W., Sc Hixson, J. E. (1999). A quantitative trait locus influencing B M I maps to the region of the beta-3 adrenergic receptor. Diabetes, 48(9), 1863-1867. Mokdad, A. H., Serdula, M . K., Dietz, W . H., Bowman, B. A., Marks, J. S., & Koplan, J. P. (1999). The spread of the obesity epidemic in the United States, 1991-1998. Journal of the American Medical Association, 282(16), 1519-1522. Neel, J. V. (1962). Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? American Journal of H u m a n Genetics, 14, 353-362. Nickerson, D. A., Taylor, S. L., Weiss, K. M., Clark, A. G., Hutchinson, R. G., Stengard J., Salomaa, v., Vartiainen, E., Boerwinkle, E., Sc Sing, C. F. (1998). D N A sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nature Genetics, 19(3), 233-240. Norman, R. A., Tataranni, P., Pratiey, R., Thompson, D., Hanson, R., Prochazka, M., Baier, L., Ehm, M . G., Sakul, H., Foroud, T., Garvey, W . T., Burns, D., Knowler, W . C , Bennett, P. H., Bogardus, C , Sc Ravussin, E. (1998). Autosomal genomic scan for loci linked to obesity and energy metabohsm in Pima Indians. American Journal of H u m a n Genetics, 62(3), 659-668. Norman, R. A., Thompson, D. B., Foroud, T., Garvey, W . T., Bennett, P. H., Bogardus, C , & Ravussin, E. (1997). Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome llqll-qll. American Journal of H u m a n Genetics, 60, 166-173. Ohman, M., Oksanem, L., Kaprio, J., Koskenvuo, M., Mustajoki, P., Rissanen, A., Salmi, J., Kantula, K., & Peltonen, L. (2000). Genome-wide scan of obesity in Finnish sibpairs reveals linkage to chromosome Xq24. Journal of Clinical Endocrinology Metabolism, 85(9), 3183-3190. Perola, M., O h m a n , M., Hiekkalinna, T., Leppavuon, J., Pajukanta, P., Wessraan, M., Koskenvuo, M., Palotie, A., Lange, K., Kaprio, J., & Peltonen, L. (2001). Quantitative-trait-locus analysis of body-mass index and of stature by combined analysis of genome scans offiveFinnish study groups. American Journal of H u m a n Genetics, 69(1), 117-123.
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Stunkard, A. J., Harris, J. R., Pederson, N. L., Sc McCleam, G. E. (1990). The body-mass index o twins who have been reared apart. N e w England Journal of Medicine 322(21) 1483-1487 Suarez, B K., Hampe, C. L., &c Van Eedewegh, P. (1994). Problems of replicating linkage claims in psychiatry. In E. S. Gershon Sc C. R. Cloninger (Eds.), Genetic approaches to mental disorders (pp. 23-46). Washington, D C : Amerkan Psychiatrk Press. Tanner, J. M., Hughes, P. C , Sc Whitehouse, R. H. (1981). Radiographkally determined widths of bone muscle and fat in the upper arm and calf from age 3-18 years. Annals of H u m a n Biology, 8(6), 495-517. *-^ TerwiUiger, J. (1995). A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. American Journal of H u m a n Genetics 56, 777-787. Vakncia, M . E., Bennett, P. H., Ravussin, E., Esparza, J., Fox, C , Si Schulz, L. O. (1999). The pima Indians in sonora, mexico. Nutritional Review, 57(5, Pt. 2) S55-S57; discussion S57-S58 Venter, J. C , Adams, M . D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., YandeU, M., Evans, C. A., Holt, R. A., Gocayne, J. D., Amanatides, P., Ballew, R. M., Huson, D. H., Wortman, J. R., Zhang, Q., Kodha, C. D., Zheng, X. H., Chen, L., Skupski, M., Subramanian, G., Thomas, P. D., Zhang, J., Gabor Miklos, G. L., Nelson, C , Broder, S., Clark, A. G., Nadeau, J., McKusick, V. A., Zinder, N., Levine, A. J., Roberts, R. J., Simon, M., Slayman, C , HunkapUler, M., Bolanos, R., Delcher, A., Dew, I., Fasulo, D., Flanigan, M., Florea, L., Halpern, A., HannenhaUi, S., Kravitz, S., Levy, S., Mobarry, C , Reinert, K., Remington, K., Abu-Threideh, ]., Beasley, E., Biddick, K., Bonazzi, V., Brandon,. R., CargiU, M., Chandramouhswaran, L., Chariab, R., Chaturvedi, K., Deng, Z., Di Francesco, V., Dunn, P., EUbeck, K., Evangehsta, C , Gabrielian, A. B., Gan, W., Ge, W., Gong, F., Gu, Z., Guan, P., Heiman, T. J., Higgins, M . E., Ji, R. R., Ke, Z., Ketchum, K. A., Lai, Z., Lei, Y., Li, Z., Li, J., Liang, Y., Lin, X., Lu, F., Merkulov, G. V, MUshina, N., Moore, H. M., Naik, A. K., Narayan, V. A., Neelam, B., Nusskern, D., Rusch, D. B., Salzberg, S., Shao, W., Shue, B., Sun, J., Wang, Z., Wang, A., Wang, X., Wang, J., Wei, M., Wides, R., Xiao, C , Yan, C , Yao, A., Ye, J., Zhan, M., Zhang, W., Zhang, H., Zhao, Q., Zheng, L., Zhong, F., Zhong, W., Zhu, S., Zhao, S., GUbert, D., Baumbueter, S., Spier, G., Carter, C , Cravehik, A., Woodage, T., Ah, F., An, H., Awe, A., Baldwin, D., Baden, H., Barnstead, M., Barrow, L., Beeson, K, Busam, D., Carver, A., Center, A., Cheng, M . L., Curry, L., Danaher, S., Davenport, L., Desikts, R., Dietz, S., Dodson, K., Doup, L., Ferriera, S., Garg, N., Gluecksmann, A., Hart, B., Haynes, J., Haynes, C , Heiner, C , Hladun, S., Hostin, D., Houck, J., Howland, T., Ibegwam, C , Johnson, J., Kalush, F., Kline, L., Roduru, S., Love, A., Mann, F., May, D., McCawley, S., Mcintosh, T., McMuUen, L., Moy, M., Moy, L., Murphy, B., Nelson, K., Pfannkoch, C , Pratts, E., Puri, V., Qureshi, H., Reardon, M., Rodriguez, R., Rogers, Y. H., Romblad, D., Ruhfel, B., Scott, R., Sitter, C , Smallwood, M., Stewart, E., Suang, R., Suh, E., Thomas, R., Tint, N. N., Tse, S., Vech, C , Wang, G., Wetter, J., WiUiams, S., Williams, M., Windsor, S., Winn-Deen, E., Wolf, K., Zaveri, J., Zaveri, K., AbrU, J. F., Guigo, R., CampbeU, M . J., Sjolander, K. V., Karlak, B., Kejanwal, A., Mi, H., Lazareva, B., Hatton, T., Natechania, A., Diemer, K., Muruganujan, A., Guo, N., Sato, S., Bafna, V., Istrail, S., Lippert, R., Schwartz, R., Walenz, B., Yooseph, S., AUen, D., Basu, A., Baxendale, J., Blick, L., Caminha, M., CarnesStine, J., Caulk, P., Chiang, Y. E., Coyne, M., Dahlke, C , Mays, A., Dombroski, M., Donnelly, M., Ely, D., Esparham, S., Fosler, C , Gire, H., Glanowski, S., Glasser, K., Glodek, A., Gorokhov, M., Graham, K., Gropman, B., Harris, M., HeU, J., Henderson, S., Hoover, J., Jennings, D., Jordan, C , Jordan, J., Kasha, J., Kegan, L., Kraft, C , Levitsky, A., Lewis, M., Liu, X., Lopez, J., M a , O., Majoros, W., McDaniel, J., Murphy, S., Newman, M., Nguyen, T., Nguyen, N , Nodell, M., Pan, S., Peck, I., Peterson, M., Rowe, W., Sanders, R., Scott, J., Simpson, M., Smith, T., Sprague, A., StockweU, T., Turner, R., Venter, E., Wang, M., Wen, M., W u , D., W u , M., Xia, A., Zandich, A., Si Zhu, X. (2001). The sequence of thee human genome. Science, 291(5507), 1304-1351. Walder, K., Hanson, R., L., Kobes, S., Knowler, W . C , Sc Ravussin, E. (2000). A n autosomal genomic scan for loci linked to plasma leptin concentration in Pima Indians. International Journal of Obesity Related Metabolic Disorders, 24(5), 559-565.
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5
Confronting
the Toxic
Environmental Actions
a n d
in a
Environment:
Public
W o r l d
Health
Crisis
KATHERINE BATTLE H O R G E N KELLY D. B R O W N E L L
The rapid increase in the prevalence of obesity has led the World Health Organization ( W H O ) to declare a global obesity epidemic ( W H O , 1998). Based on data from the National Health and Nutrition Examination Surveys, researchers at the National Center for Health Statistics report that almost 5 5 % of U.S. adults are overweight (i.e., their body mass index [BMI] is greater than or equal to 25 kg/m^) and 2 2 . 5 % are obese (i.e., their B M I is greater than or equal to 30 kg/m^) (Flegal, CarroU, Kuczmarski, & Johnson, 1998). The prevalence a m o n g middle-aged western Europeans is 1 5 % - 2 0 % , w h U e in eastern Europe some countries face rates as high as 4 0 % - 5 0 % (Bjorntorp, 1997). As the availability of fast, inexpensive, energy-rich foods grows and physical activity declines, obesity rates continue to increase in countries across the world. The prevalence of obesity increases even in the face of broad publicity about the problem, tremendous pressure to be thin, and multiple industries focused on dieting and weight control. In the United States alone, health clubs, diet centers, and low-fat snacks fuel a $33billion-a-year weight control industry (Food and Nutrition Board, 1995), but obesity rates have grown in every segment of the population (Flegel et al., 1998). In a U.S. population study comparing the period 1976-1980 to the period 19881991, investigators reported decreases in average daily fat intake from 4 1 % to 3 6 . 6 % of total calories and in daily caloric intake from 1,854 kilocalories (kcal) to 1,785 kcal (Heini & Weinsier, 1997). Yet there has been a dramatic rise in obesity (Food and Nutrition Board, 1995). Based on reports that the percentage of Americans consuming low-calorie products has risen from 1 9 % in 1978 to 7 6 % in 1991, and that the percentage of Americans leading a sedentary lifestyle ( 6 0 % ) did not change between 1986 and 1991, a decrease in the prevalence of obesity would be expected (Heini & Weinsier, 1997). Underreporting of fat and caloric intake m a y account for this anomaly, but it is 95
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clear that low-fat foods, health clubs, and weight loss programs are not solving the obesity crisis. Nothing is solving this crisis. Researchers estimate the annual deaths in the United States attributable to obesity at approximately 325,000 (Allison, Fontaine, Manson, Stevens, & VanltaUie, 1999). These mortality rates approach the approximately 400,000 tobacco-related deaths annually in the United States (Centers for Disease Control and Prevention, 2000). Obesity has been associated with coronary heart disease, diabetes, some cancers, stroke, hypertension, high blood cholesterol, gallbladder disease, respiratory disease, and arthritis (Must et al., 1999; PiSunyer, 1995; see also Field, Barnoya, & Colditz, Chapter 1, this volume). Wolf and Colditz (1998) estimated health care costs attributable to obesity at $99.2 bUhon in 1995. This figure represents approximately $51.6 bUlion in direct medical costs and $47.6 billion in indirect expenditures—a total that constitutes 5 . 7 % of the annual U.S. health care cost. Over a 6-year period, the frequency of obesity-related doctor visits has increased 8 8 % (Wolf, 1998).
LIMITATIONS O F T R E A T M E N T Nearly all approaches to weight loss focus on the individual. Even if these were effective, the number of people w h o receive treatment is small. Weight loss attempts that were initially considered successful frequently result in weight regain (Stunkard, 1996; Wing, 1998). Only surgery, recommended for the most extreme cases of morbid obesity, has shown longterm success on a broad level (Sjostrom, Lissner, Wedel, & Sjostrom, 1999; Stunkard, 1996). A study of weight loss through fasting found that 9 8 % of the individuals had returned to pretreatment weight after 9 years (Drenick & Johnson, 1978), while an examination of behavioral self-management training showed that only about 5 % of patients achieved long-term weight loss maintenance (Goodrick &c Foreyt, 1991). Although some behavioral treatments show successful maintenance for up to 2 years, longer-term followup studies indicate a trend of gradual return to baseline weight over time (Wilson, 1995). Douketis, Feightner, Attia, and Feldman (1999) reviewed weight loss trials and also found a pattern of initial weight loss followed by gradual weight regain. Several pharmacological treatments for obesity have been developed, and some have produced weight loss. However, the long-term effects of these drugs have not been studied, and given the chronic nature of obesity, it can only be assumed that weight regain will follow w h e n the medication is discontinued. Obesity has m a n y causes; hence it is unlikely that any medication can override all the relevant systems and provide a solution for the disease. Treatment efticacy in studies is low, and treatment effectiveness for the general population is very low, as treatment for weight loss is costiy and available to a select few (Horgen & BrowneU, 1998). It is time to consider an alternative approach to the obesity epidemic.
THE INDIVIDUAL, BIOLOGY, AND THE ENVIRONMENT There are three logical places to look when explaining the causes of obesity and identifying areas for its treatment or prevention: the individual, biology, and the envhonment. Obesity is multiply determined, so all these factors contribute to etiology. Every intervention derived for any of these areas should be enlisted in the fight. It is apparent, however, that if the tide of the obesity epidemic is to be halted (much less reversed), w e must rely on advances in prevention, not treatment. The question, then, is whether the individual, biology, or the environment offers the
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greatest hope for prevention. It would be hard to imagine more pressure on individuals to be thin. Nutrition and physical activity education programs in the schools, again aimed at individuals, have not been very effective. W e r e they effective, it is unlikely that schools, with the great demands placed on them, would place nutrition and physical activity as top priorities in any systematic way. Focusing on individuals m a y help selected people, but does not offer m u c h hope for helping the obese society. Biology is thought to explain 2 5 % - 4 0 % of the variance in population body weight (Bouchard, 1995). At s o m e point, biology m a y explain which individuals in an obesityprone environment will in fact become obese, and m a y explain differences between people in the extent of obesity reached in response to a c o m m o n environment. But biology does not explain the world problem any more than understanding biological vulnerabilities in individuals explains w h y there is so m u c h lung cancer. There is so m u c h lung cancer primarily because of tobacco, and there is so m u c h obesity because of a dangerous food and physical activity environment.
THE E N V I R O N M E N T A S A CAUSAL FACTOR: WORLDV^IDE EVIDENCE The United States is not alone in its fight against obesity. During the past several years, obesity has hit epidemic proportions in both developed and developing countries, affecting residents of countries previously considered poor as well as those with higher income levels (VanltaUie, 1994; W H O , 1998). Countries once plagued with issues of undernutrition must n o w face the problems associated with overweight (Popkin &c Doak, 1998). T h e increasing prevalence of obesity in country after country suggests that the genesis of the problem supersedes biology. Although the problem exists in a wide range of environments, the underlying similarities are clear: shifts in physical activity and eating patterns (Popkin & Doak, 1998). Popkin and D o a k (1998) note that the increased level of obesity in countries as varied as Mexico, South Africa, Malaysia, and nations of the western Pacific underscores the need to focus on the underlying environmental causes of obesity rather than simply on genetic factors. In some Native American tribes and American Pacific Islanders, as well as in Australian Aborigines and Polynesians, obesity rates approaching 8 0 % have been noted (Bjorntorp, 1997). Despite variations in socioeconomic and behavioral factors, countries across the world are moving toward environments that promote obesity ( W H O , 1998). Bjorntorp (1997) notes that poverty is associated with greater prevalence of obesity in developed countries, but that affluence is linked to greater obesity prevalence in developing nations. Research o n a variety of cultures illustrates this diathesis-stress model of obesity. M a n y researchers cite migration studies as examples of the deleterious effects of Westernized eating habits o n individuals. W h e n Chinese, Japanese, or Filipina w o m e n m o v e to the United States, their risk of breast cancer increases over several generations to equal that for w o m e n of European descent in the United States (who have rates traditionally four to seven times higher) (Ziegler et al., 1996). T h e investigators determined, after adjustment for breast cancer risk factors, that weight change is a critical factor in this increased risk for breast cancer (Ziegler et al., 1996). In a study of nutrition-related diseases and disorders among immigrants, W a n d e l (1993) focused on dietary change after migration and cited evidence that immigrants are especially susceptible to diseases related to overnutrition, such as coronary heart disease and non-insulin-dependent diabetes. In sum, immigrant groups tend to have m o r e obesity than people remaining in their native countries. The Pima Indians provide a basis for comparison between genetically similar people hving in different environments. Ravussin, Valencia, Esparza, Bennett, and Schulz (1994)
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reported an average BMI of 35 kg/m^ for Pima women living in Mexico, compared to 37 kg/m^ for those living in Arizona. The average w o m a n weighed 4 4 pounds more in Arizona. Bhatnagar, Anand, Durrington, Patel, and W a n d e r (1995) found similar results w h e n they compared individuals w h o had migrated to west London with biological relatives w h o remained in Punjab, India. W h e n the environment changes, weight changes. VanltaUie (1994) proposes that migration, urbanization, n e w eating habits, and affluence m a y contribute to the growing prevalence of obesity in developing countries; he notes that the obesity epidemic will continue with inevitable modernization. In its recent report on the world obesity problem, the W H O (1998) concurs. Even those w h o choose to remain in their countries of origin face growing exposure to Western culture. M o r e processed, packaged, and high-calorie foods are becoming available. The eagerness of fast-food franchises to expand has led to their increased presence in countries across the globe. Although in Europe some groups have expressed concern about fast food impinging on the history and culture of the area, the job creation and promotional spending accompanying expansion—not to mention the cheap, tasty food—have enticed m a n y to welcome fast-food chains (Tagliabue, 1999). A s the French diet, once touted for its healthiness, has become "more Americanized" (Brody, 1999) to contain more snacks, more meat, and more fast foods, French cholesterol levels have risen. O n e expert predicts that the French will soon experience a rate of coronary death approaching that of Americans as the American diet and hfestyle continue to invade the country (Brody, 1999). A study on the diet and activity of Chinese adults indicated that increased B M I paralleled increased energy and fat consumption (Paeratakul, Popkin, Keyou, Adair, & Stevens, 1998). The authors attributed the higher levels of obesity to increased fat consumption, which they noted can increase weight even in a survey population consisting primarily of rural residents with high levels of physical activity and physically demanding jobs. They noted that because obesity is often associated with affluence in China and m a n y developing countries, those experiencing weight gain m a y not perceive the gain as a health hazard. A prospective Japanese study concluded that childhood obesity is becoming a major public health concern in Japan, and that approximately 5 0 % of children w h o were obese in primary school were obese at age 17 (Sugimori et al., 1999). In Kuwait, the high proportion of overweight children and adults has led the Ministry of Health to promote weight loss with the slogan "Food damages your health" (Kandela, 1999).
W H Y THE ENVIRONMENT H A S BEEN IGNORED As the environment worsens, so does obesity. Biology permhs obesity to occur in individuals, but the environment causes obesity in the culture. Thefieldhas been preoccupied with w h y individuals are obese and h o w to help them, rather than with w h y society is obese and h o w to help it.
Cultural Attributions and Lack of Public Health Attention We can only speculate why such obvious factors as a poor food and physical activity environment have been ignored. Part of the reason has been the cultural attribution of fauh to obese individuals. This has led to widespread bias, stigma, and discrimination, but alsomore pertinent to this chapter—to lack of attention to the environment. In addition, public health experts have focused primarily on infectious diseases and only more recently have begun to address chronic diseases. Only during the past few years have more than a handful of researchers and health officials called for obesity to be considered a chronic disease; attri-
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bution of the problem to the environment and calls for environmental action are even more recent (BrowneU, 1994).
The Pervasiveness of the Toxic Environment
It is little wonder that approaches to weight loss focusing on the individual have yielded less than impressive results, given the environment. W e (Brownell, 1994; Horgen & Brownell, 1998) have proposed that Americans are exposed to a "toxic environment," which pervasively surrounds them with inexpensive, convenient foods high in both fat and calories. Egger and Swinburn (1997) suggest that obesity is "a normal response to an abnormal environment" (p. 477). There are m a n y examples of the ever-worsening environment. Fast-food chains across the globe continue to increase serving sizes, inducing patrons to ingest extra fat and calories through packaged "value" meals. M a n y restaurants offer staggering portion sizes, sometimes large enough to feed two or three people, citing customers' appreciation for value. Fast-food chains market directly to children with advertising campaigns using recognizable characters, such as cartoon and movie figures. Hager (1998) noted Burger King executive Richard Tyler's statement that "Providing kids with twice the number of toys . . . doubles the reasons for kids to visit our restaurant," and the manager of Burger King's Youth and Family Division's claim that "Kids of all ages will be able to share in the excitement generated by the M I B [Men in Black] phenomenon . . . what kid would want to be without the official M e n in Black gear or other official M I B toys that will be offered with every kid's meal?" Ronald M c D o n a l d is k n o w n to 9 6 % of children in the United States and across the globe, and he speaks over 20 different languages (Hager, 1998, p. 758). Young children m a y not be capable of distinguishing between television programming and advertising (Martin, 1997). Research has indicated a link between obesity and television viewing, showing a dose-response relationship between hours of television viewed and obesity (Dietz &c Gortmaker, 1985). The majority of television advertisements are for food products, and most of the foods advertised are sugared cereals, fast food, candy, and soft drinks (Dibb, 1996). Studies have shown that television viewing hours are related to caloric intake of children as well as to food requests by children and food purchases by parents (Taras, Sallis, Patterson, Nader, & Nelson, 1989). Television contributes to obesity both by encouraging children to buy food of low nutritional value, and by enticing them to spend time in a sedentary activity rather than doing something that burns calories (Horgen, Choate, & Brownell, 2001). N o t only are children sitting inactive while watching television, but they are also likely to be snacking while doing so. Several advocacy groups have formed to encourage regulation of advertising to children. In 1996, the Federal Communications Commission strengthened the Children's Television Act of 1990 by requiring broadcasters to show a specific amount (at least 3 hours per week) of programming designed to "educate and inform" (Center for Media Education [CME], 1999, p. 1) chUdren aged 2-16. The C M E (1999) issued a report that reviewed the various methods broadcast stations have chosen for complying with the regulations, and that encouraged parents to be actively involved in monitoring broadcasters' compliance. Some children are barraged by food advertisements in school as well as at home. Schools broadcast Channel O n e — a 10-minute news program with 2 minutes of commercials—to over 8 million middle and high school children, in return for televisions, V C R s , and satellite dishes for the schools (Consumers Union, 1996; Mifflin, 1998). Brand and Greenberg (1994) found that 6 9 % of the 45 commercials shown on Channel O n e during a 4-week period were for food products such as fast food, g u m , candy, soft drinks, and snack chips. The study also found that advertising contributed to students' positive atthudes to-
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ward the products advertised, as well as to their intentions to buy the products, compared to students w h o did not see Channel One. This in-school advertising, combined with the widespread introduction of fast food into school cafeterias and the availability of soft drink, candy, and snack machines, produces a very risky environment for school chUdren. A n American School Food Service Association survey of over 400 schools reported that pizza was the most popular lunch entree at 6 6 % , followed by chicken nuggets at 2 0 % (Hager, 1998). N o t only are Pizza H u t and Domino's competing to supply the pizza, but fast-food restaurants such as Taco Bell are entering cafeterias in alarming numbers. Kids w h o eat fast food for lunch are likely to do so for dinner as well. Children consume 8 5 % of their meals eaten out of the h o m e at fast-food restaurants, and $5 of every $10 spent on restaurant food in the United States is spent on fast food (Hager, 1998). Thirty-eight million people eat at McDonald's across the world daily, so the $588 bUlion spent by McDonald's on 1996 advertising and promotion seems to be effective (Hager, 1998). The more important question is this: H o w is it affecting us?
P R E V E N T I O N A N D PUBLIC P O L I C Y F O R O B E S I T Y Earlier Prevention Efforts The equivocal success of weight loss efforts focusing on the individual has led to calls for increased attention to prevention. Examples are the community heart disease prevention programs aimed at changing a number of behaviors related to risk, including diet. Three such prospective cohort design studies compared individuals w h o participated in seminars, education packages, and mass media programs to persons in control communities w h o received no programs, and found no differences in the average weight of intervention and control communities at 3- to 7-year follow-ups (Fortmann, Williams, HuUey, Haskell, & Farquhar, 1981; Jeffery, 1993; Taylor et al., 1991). Douketis and coUeagues (1999) cite high withdrawal rates, self-reports of weight, and no well-defined criteria for successful outcome as methodological problems with these studies. Focusing on individuals, the Pound of Prevention Study randomly assigned participants to no contact, newsletter education, or education plus incentives, and found that although weight gain in the contact groups was lower than that in the no-contact group at annual weighings up to 3 years, weight gain after 3 years did not differ significantly between contact and no-contact groups (Jeffery & French, 1999). Education aimed at either individuals or entire communities has not been effective with respect to weight. Despite a U.S. Public Health Service objective outiined in Healthy People 2000 that the increase in obesity prevalence be halted (U.S. Department of Health and H u m a n Services, 1991), the epidemic continues to grow. Attempts to halt the obesity epidemic through a focus on genetics and individual behavior change have not produced substantial results. Attempts at prevention aimed at individuals are in their infancy and have not been effective. It is clear that w e must focus our attention on n e w approaches to combating obesity. The toxic environment is a logical target.
Proposals for Combating the Toxic Environment The toxic environment contributes to obesity through both energy intake and energy expenditure. Proposals for environmental interventions should address both sides of the obesity equation.
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Researchers have noted that, given the limited success of current efforts at psychoeducation, pubUc information alone is unhkely to have an appreciable impact on behavior unless it is combined with some form of structural change to counteract poor diet and sedentary lifestyle (BrowneU, 1994; Foreyt & Goodrick, 1995; Horgen & Brownell, 1998). A call has been m a d e for obesity researchers to w o r k with public health officials, legislators, and the food industry to achieve results (Brownell, 1994; Horgen & BrowneU, 1998; Jeffery, 1995). Egger and Swinburn (1997) noted the importance of examining the environment at both a "macro" level (the population at large) and a "micro" level (the individual), citing the interconnected nature of the sectors. Changes at the macro level, such as policies of food manufacturers and costs of products, greatly affect choices at the micro level, such as the ability of a restaurateur to offer specials on healthy products. W e offer specific proposals for broad-scale change created by education, legislation, and regulation. S o m e have been discussed previously (Brownell, 1994; Horgen & BrowneU, 1998). Little w o r k has been done to test whether these would be successful. O n e problem is that almost no research has been done on environmental causes of obesity or environmental means for its prevention. This is a glaring deficit in the funding picture. W e issue these proposals as a means of promoting discussion on environmental interventions. Such discussions are needed desperately, if only to produce policy suggestions superior to ours. 1. Provide resources for physical activity. Even if Americans are eating fewer calories and less fat, daily energy expenditure has decreased due to the near-ubiquity of televisions, video games, computers, remote controls, automobUes, and other energy-saving devices. It is imperative that Americans have easy access to resources for physical activity. Access alone, however, will probably not be sufficient. Even those with access to exercise facilities do not use them enough. Incentives for exercise, such as discounted health care rates, might provide excellent motivation. Frequent-flyer programs that offer g y m patrons airline miles based on time spent using exercise equipment are a creative option. S o m e insurance companies have also begun reimbursing members for exercise facility fees, based on members' completing a m i n i m u m number of visits (Oxford Health Plans, 1999). Increasing physical activity requirements in schools m a y also be a key to promoting a healthier lifestyle. 2. Regulate food advertising directed at children. Food advertising directed at children takes advantage of a population lacking the capability to m a k e informed decisions. Children's purchase requests based on the sugared cereals and fast foods advertised on television translate into poor choices for the entire family. O n e particularly useful approach might be to mandate time for messages promoting nutrition and activity to counter advertisements promoting unhealthy behavior (Horgen et al., 2001) 3. B a n food advertising in schools. School children are unwitting targets of advertising couched as education in schools. Even children whose parents protect what they watch at home cannot be shielded from advertising at school. 4. Prohibit the sale of fast foods and soft drinks in schools. School food service is often an enterprise aimed at satisfying the customers, and customers are m a d e happy mainly w h h poor foods. Food service must become part of a child's education. Children do not need fast food and soft drinks in the schools. Justifying these foods by citing consumer wishes makes no more sense than installing cigarette machines because children smoke. True, selling cigarettes to minors is illegal and offering them poor foods is not, but the two activities m a y rival each other in the toll they take on health. 5. Subsidize healthy foods such as fruits and vegetables. Research has shown that pricing incentives encourage healthier food choices. French, Jeffery, Story, H a n n a , and Snyder
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(1997) found that when the prices of low-fat foods in a vending machine were reduced by 5 0 % , sales of the low-fat items increased from 2 5 . 7 % of machine sales to 4 5 . 8 % , then decreased to 2 2 . 8 % w h e n the prices returned to normal. A cafeteria study reduced fruit and salad prices by 5 0 % and found that sales of these items increased threefold while sales of other items remained constant (Jeffery, French, Raether, & Baxter, 1994). Lower price decreases have also been effective in encouraging healthier choices. A restaurant study lowering prices 2 0 % - 3 0 % found that sales increased significantly over those at baseline and decreased w h e n prices returned to normal (Horgen, 2000). 6. Tax unhealthy foods. Taxes can encourage healthy eating, both by providing money for subsidies of healthy foods and by discouraging the consumption of foods low in nutritional value. Previous food taxes have not been earmarked for subsidies for healthy foods, and they have been crhicized as regressive. O n e could argue that the current pricing structure, which makes healthy foods more expensive than less healthy foods, forces those with lower incomes to eat poorly and is itself regressive. A tax on unhealthy foods with revenues designated for subsidies could reverse this harmful pricing structure. Such taxes have been enacted in several states, but they have not been w e U received. In 1991, California levied an 8.25% tax on "nonessenrial" foods (Zuck, 1992). Although the tax generated approximately $200 million during the first year, it was largely unpopular and was repealed in December 1992. Maryland's 5 % snack food tax was enacted in 1992 (Abramowitz, 1995; Harrison, 1993) and repealed effective July 1997 (Maryland ComptroUer of the Treasury, 2000). The tax received widespread opposition from the Snack Food Association, which represents snack manufacturers and suppliers to the snack food industry. Maine imposed a 7 % tax on "nonnutritious" foods, instituted in 1991 (Zuck, 1992). Maine lawmakers repealed the tax in 2000 (Higgins, 2001). Critics have attacked the taxes as regressive (Lozano, 1991), arbitrary in their classification of foods (Garry, 1992), and difficult for retailers to impose (Gasparello, 1991). The taxes were never evaluated, but judging by the fierceness of the opposition from snack food companies, they might be expected to have an effect. Although there is m u c h room for improvement in the design of such taxes, it is also clear that they generate substantial revenue. They might be improved through a classification system based on clearer nutritional guidelines and a designation of revenues for healthy food and exercise projects. There is also the possibility, if taxes large enough to change food consumption are not acceptable, of using smaller taxes to generate funds for programs aimed at altering diet and activity patterns. Jacobson and Brownell (2001) have noted that a number of cities and states have imposed taxes on soda pop or snack foods. The taxes are smaU enough (usually several cents per can or bottle) to minimize resistance, but the consequence has been many millions of dollars in revenue. Currently the monies are earmarked for work irrelevant to diet and physical activity (e.g., budding roads), or are not earmarked at all. Jacobson and Brownell (2001) propose specific earmarking of such m o n e y for nutrition education or other similar programs. 7. Increase awareness of the obesity epidemic. Twenty years ago, few would have heeded warnings about tobacco or beheved that smoking would be Ulegal in m a n y public places. Only through widespread education about the health and financial costs of the problem did the campaign against tobacco gain public support. With mortality from obesity approaching that related to tobacco, and health care costs increasing, an analogy between smoking and obesity is not only useful but unavoidable. 8. Involve parents in the protection of their children. M a n y parents do not k n o w that theh children are targets of advertising in school. They are also unaware of the extent of the focus on their children by the fast-food industry. Children w h o are obese are
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at increased risk of becoming obese adults (Whitaker, Wright, Pepe, Seidel, & Dietz, 1997), and parents can play a role in helping their children avoid a painful struggle with obesity.
FUTURE DIRECTIONS By drawing attention to the toll that obesity takes on America's physical and mental health, as well as on the American health care budget, public advocates can gain support for action at the environmental level. A survey of community attitudes toward public policy approaches to alcohol, tobacco, and food control indicated that the public favored regulatory controls in aU three areas, although support w a s greater for alcohol and tobacco regulation than for food control intervention (Jeffery et al., 1990). The regulation most strongly supported w a s that designed to protect children, followed by advertising restriction and control over sales conditions. A survey of over 700 mothers of elementary school children revealed significant concerns with the nutritional content s h o w n in food advertising toward children (Grossbart & Crosby, 1984). T h e authors delineate suggestions to food advertisers, including direct appeals to children to be conscious about nutrition and to be responsible consumers. They also advocate advertising messages showing respect for parental authority. A n overview of health psychology and public pohcy noted that from 1985 to 1995, health care costs grew more than any other segment of the economy (DeLeon, Frank, & Wedding, 1995). T h e researchers cite efforts to contain health care costs through public and preventive measures as paramount. W e agree, and feel that the obesity field is in desperate need of such a mentality. It is clear that obesity has become a national epidemic, and that worldwide rates of obesity continue to expand at alarming rates. The limited success of interventions focused on the individual indicates that it is time to approach the problem from a different perspective. The environment provides numerous opportunities for intervention and stands as a largely untapped resource for relief from the obesity epidemic.
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a n d
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S y n d r o m e
ALBERTJ. STUNKARD
This chapter describes the relationship of obesity to the eating disorders. For m a n y years this relationship has been unclear. At times even obesity itself w a s considered an eating disorder—a result of disordered overeating that affected all obese persons indiscriminately. This view became particularly popular during the 1970s, w h e n the advent of behavior therapy had effects on food intake and body weight, almost regardless of differences a m o n g obese persons. A s w e learned more about eating disorders, however, it became clear that there were major differences in eating behavior a m o n g obese individuals. For the majority, overeating fitted n o specific pattern. For a minority, however, two eating disorders that contribute to obesity have been identified: binge-eating disorder and the night-eating syndrome.
BINGE-EATING DISORDER Diagnostic Criteria A m o n g disorders of eating, binge eating (or its cognate, bulimia) has by far the longest history. Bulimia (literally, "ox hunger") w a s recognized by Hippocrates as a sick hunger, distinct from normal hunger (Stunkard, 1993). Reports during the past century have mentioned bulimia, usually as eating binges, but at times also as the associated vomiting and purging. In 1959 a diagnosis, binge-eating syndrome, w a s proposed (Stunkard, 1959). T h e cardinal feature of this syndrome w a s bingeing, which has been defined as "eating, in a discrete period of time . . . , an amount of food that is definitely larger than most individuals would eat under simUar circumstances" (American Psychiatric Association [APA], 1994, p. 731). The concept of binge eating, without the purging, vomiting, exercise, and fasting associated with bulimia nervosa, w a s advanced by the proposal by Spitzer and colleagues (1992) of the diagnosis of binge-eating disorder. T h e propositi was based o n data from a
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large number of clinical and nonclinical programs dealing with eating disorders, which yielded t w o samples of 1,984 and 1,785 subjects. T h e data had acceptable psychometric properties and showed coherence a m o n g the characteristics of the disorder: "recurrent episodes of binge eating associated with subjective and behavioral indicators of impaired control over, and significant distress about, the binge eating and the absence of the regular use of inappropriate compensatory behaviors" ( A P A , 1994, p. 729). T h e fuU criteria for binge-eating disorder that were first proposed by Spitzer and colleagues (1992) are stiU used (see Table 6.1).
Associated Features Initial reports proposed that persons with binge-eating disorder, compared to control groups of obese persons, had (1) m o r e severe obesity; (2) earher onset of overweight; (3) earlier onset of, and m o r e frequent, dieting; and (4) greater psychopathology, including depression, substance use disorders, and emotional problems (Spitzer et al., 1992; Spitzer, Stunkard, et al., 1993; Spitzer, Yanovski, et al., 1993). Despite these reports and others noted below, binge-eating disorder is included only in an appendix of the Diagnostic and Statistical M a n u a l of Mental Disorders, fourth edition ( D S M - I V ; A P A , 1994) as a proposed diagnosis requiring further study; it can be formally diagnosed only as "eating disorder not otherwise specified." T h e publication of the Spitzer and colleagues papers w a s followed by an increase in the already rapid publication rate of studies of binge eating. Although there were some disagreements about the characteristics of binge-eating disorder in the earlier papers, extensive research has resulted in a consensus as to the major characteristics of binge-eating disorder. This consensus supports the propositions of the Spitzer and coUeagues research (see above). In support of the first proposition, Telch, Agras, and Rossiter (1988) and
T A B L E 6.1. Proposed Diagnostic Criteria for Binge-Eating Disorder A. Recurrent episodes of binge eating. An episode of binge eating is characterized by the following: (1) eating, during a discrete period of time (e.g., within any 2-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time under similar circumstances (2) a sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating) B. The binge-eating episodes are associated with three (or more) of the following: (1) eating much more rapidly than normal (2) eating until feeling uncomfortably full (3) eating large amounts of food when not feeling physically hungry (4) eating alone because of being embarrassed by how much one is eating (5) feeling disgusted with oneself, depressed, or very guilty after overeating C. Marked distress regarding binge eating is present. D. The binge eating occurs, on average, at least 2 days per week for 6 months. .
E. The binge eating is not associated with the regular use of inappropriate compensatory behaviors (e.g purging, fasting, excessive exercise) and does not occur exclusively during the course of Anorexia Nervosa or Bulimia Nervosa. Note. From American Psycliiatric Association (2000). Copyright 2000 by the American Psychiatric Association. Reprinted by permission.
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Marcus, Wing, and Lamporski (1985) have shown a strong relationship between body mass index and the frequency of bingeing. Supporting the second and thhd propositions, Marcus, Amith, Santelh, and Kaye (1992) and Yanovski (1993) have found an eariier onset of both overweight and dieting in binge-eating disorder. In support of the fourth proposition, Marcus, W i n g , and Hopkins (1988), Marcus and colleagues (1996), Yanovski, Nelson, Dubbert, and Spitzer (1993), and MitcheU and Mussell (1995) have shown greater psychopathology (especially depression) in persons with binge-eating disorders than in those w h o do not binge-eat, and W a d d e n , Foster, and Letizia (1994) and Kuehnel and W a d d e n (1994) have confirmed the increased prevalence of depression. Marcus and colleagues (1992), W U s o n , Nonas, and Rosenblum (1993), and Wilfley, Schwartz, Spurrell, and Fahburn (2000) have reported that persons with binge-eating disorder have weight and shape concerns comparable to those of persons with bulimia nervosa, and far higher than those in an obese control group. A study by Tanofsky, Wilfley, Spurrell, Welch, and Brownell (1997) suggested that m e n with binge-eating disorder are significantly more likely to manifest substance use disorders. The widely varying estimates of the prevalence of binge-eating disorder derive at least in part from problems in defining the essential behavior of the disorder—the binge. Fairburn and Cooper (1993) have proposed that a binge comprise at least two elements: an objective component (i.e., the amount of food consumed) and a subjective component (i.e., a sense of loss of control). There is general agreement on the subjective aspect of the binge— the feeling of loss of control. By contrast, there is often disagreement about the objective aspect—the size and duration of a binge. The disagreement is reflected in the aforementioned arbitrary and imprecise definition of the size of the binge: "an amount of food that is definitely larger than most individuals would eat." The disagreement is also reflected in the duration of a binge. In contrast to the purging type of bulimia nervosa, in which a binge is clearly terminated by an episode of purging, termination of a binge in binge-eating disorder often has no clear demarcation. Accordingly, it has been assigned an arbitrary duration of 2 hours. This duration requirement is inadequate. Marcus and coUeagues (1992), for example, reported that almost 2 5 % of binge-eating episodes in binge-eating disorder lasted an entire day. A feature of binge-eating disorder that is particularly relevant to obesity is that persons with this disorder s h o w a general tendency to overeat, in addition to their binges. In other words, their binges occur against a background of overeating. This pattern is in sharp contrast to the eating patterns of persons with bulimia nervosa, in which binges occur against a background of extreme dietary restraint.
Risk Factors The proliferation of diagnoses in successive issues of the D S M has been based upon the APA's presumption that more precise diagnosis wiU lead to better understanding of disordered behavior. Such understanding has been advanced by the large-scale, communitybased, case-control survey of Fairburn and colleagues (1998). It showed that bingeeating disorder w a s associated with exposure to risk factors in two different domains: psychiatric disorder and obesity. Compared with risk factors for bulimia nervosa, those for binge-eating disorder were weaker and more circumscribed. Compared to heahhy control subjects, however, persons with binge-eating disorder showed greater parental depression; vulnerability to obesity; repeated exposure to negative comments about shape, weight, and eating; morbid perfectionism; and negative self-evaluation. Compared to subjects with other psychiatric disorders, they more often reported childhood obesity and negative comments about shape, weight, and eating.
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A great deal of attention has been directed toward the possibility that dieting is a risk factor for binge-eating disorder. Thus it has been proposed that binge eating is a result of dieting (Herman & Polivy, 1980, 1990), that dieting is a "precondition" for the development of binge eating (Marcus et al., 1988), and that attempts at weight loss m a y exacerbate binge eating (Garner & Wooley, 1991; Polivy &C H e r m a n , 1985). Interest in the possibility that dieting is a risk factor for binge-eating disorder arose from its similarity to bulimia nervosa. Dieting has been implicated in the genesis of bulimia nervosa (Polivy &c H e r m a n , 1985; Polivy, H e r m a n , Olmsted, &c Jazwinski, 1984), and since bingeing occurs in both, it seemed reasonable to implicate dieting in the genesis of bingeeating disorder. This implication has been the subject of considerable study, focused particularly on the question of which comes first—bingeing or dieting? In binge-eating disorder, very frequently dieting follows bingeing and thus can hardly have caused it. Spitzer and colleagues' first papers on binge-eating disorder (Spitzer et al., 1992; Spitzer, Yanovski, et al., 1993), described binge eating as occurring before the first diet. Wilson and coUeagues (1993) reported that bingeing preceded dieting in 6 4 % of their subjects, and no more than 9 % reported that they had been on a strict diet at the time they began bingeing. Five subsequent reports have confirmed this sequence (Abbott et al., 1998; Berkowitz, Stunkard, & StaUings, 1993; Grilo & Masheb, 2000; MusseU et al., 1997; Spurrell, Wilfley, Tanofsky, & Brownell, 1997). In the face of this evidence, what w a s the basis for the idea that dieting led to bingeing? The idea seems to have arisen from the finding that dieting led to an increase in the Restraint factor of the H e r m a n and Polivy (1980) Restraint Scale, and that this "restraint" w a s elevated in bulimia nervosa as well as in unsuccessful dieting (Herman & Polivy, 1990; Polivy & H e r m a n , 1993). But this "restraint" is a misnomer. T h e Scale's two subscales appear to measure not restraint, but disinhibition of eating behavior. T h e Weight Fluctuation subscale is associated with greater weight and the weightfluctuationsthat accompany this greater weight, as well as with dietary lapses. The Concern with Dieting subscale measures the kind of rigid dieting that has been found (Westenhoefer, Stunkard, & Pudel, 1999) to be associated with a poor outcome of dieting, and in fact this subscale is associated with unsuccessful dieting (Charnock, 1989; G o r m a n &c AUison, 1995). A key experiment in the development of the H e r m a n and Polivy (1980) Restraint Scale showed (significantly) that in response to a preload of food by persons w h o scored high on the scale, restraint was disinhibited, and subjects overate. The development of a later scale, the Eating Inventory (Stunkard & Messick, 1985), built upon the H e r m a n and Polivy (1980) scale to address problems with it. Instead of focusing on a single factor of restrained eating, construction of the Eating Inventory began with literature-based items that tapped several aspects of eating behavior. These items were administered to large groups of persons selected as being high or low in dietary restraint. Factor analysis of their responses yielded three factors, prominent a m o n g which was a factor designated Disinhibirion. It corresponded to the Concern with Diering subscale in the H e r m a n and Polivy scale, and performed clinically in m u c h the same way. A second factor on the Eating Inventory reflected Restraint, but a restraint far different from the Restraint factor of the H e r m a n and Polivy scale and one that predicted successful dieting (Charnock, 1989; G o r m a n & Allison, 1995). The differing implications of "restraint" as conceptualized by the two scales was demonstrated in the study by Yanovski and Sebring (1994). W h e n persons with bingeeating disorder were placed on reducing diets, their Restraint factor scores on the Eating Inventory increased significantly during precisely the time w h e n their rate of bingeing decreased dramatically. These authors concluded that disinhibition, rather than restraint, is a major contributor to binge eating.
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Prevalence A benefit of the delineation of binge eating has been to encourage study of its prevalence. The study is still in its infancy, as illustrated by widely varying estimates. Thefirstestimates, in the original Spitzer and colleagues papers, were that 2 9 % - 3 0 % of obese people seeking treatment for their obesity had binge-eating disorder, with the disorder being about 1.5 times more c o m m o n in overweight w o m e n than in overweight m e n (Spitzer et al., 1992). These estimates were based upon self-report questionnaires. Later interview-based studies of treatment-seeking obese persons have found a far lower prevalence. For example, m y colleagues and I found h necessary to screen 1,450 obese w o m e n , w h o had identified themselves as bingeing, in order to recruit 50 subjects w h o met interview-based criteria for binge-eating disorder (Stunkard, Berkowitz, Tanrikut, Reiss, & Young, 1996). A m o n g patients seeking treatment for obesity in other studies, the prevalences were 7 . 6 % (Stunkard, Berkowitz, W a d d e n , et al., 1996), 8.9% (Basdevant, PouiUon, & Lahlon, 1995), and 18.8% (Brody, Walsh, &c Devlin, 1994). In community studies, the prevalences were 2 % (of w h o m only half were obese; Spitzer et al., 1992) and 1.8% (Bruce & Agras, 1992).
Treatment A flood of reports of treatment for binge-eating disorder followed publication of the Spitzer and colleagues papers. These treatments have often foUowed the precedent of treatments for bulimia nervosa. The most distinctive have involved the use of cognitive-behavior therapy.
Psychological Treatments: Cognitive-Behavior Therapy and Interpersonal Therapy In 1993 Fairburn revised his manual for the treatment of bulimia nervosa to include treatment of binge-eating disorder (Fairburn, Marcus, & W U s o n , 1993). Wilfley and colleagues (1993), WUfley and Cohen (1997), and Marcus (1997) have further adapted this approach, which focuses first on the eating disturbance and the associated problematic cognitions and attitudes about eating, body shape, and weight. It emphasizes moderation in food intake so that it is neither over- nor underrestrictive, and recommends increased physical activity. Fairburn and others maintain that control of binge eating is necessary before obese persons can lose weight, and that attempts at weight loss should be deferred until binge eating has been controlled. Cognitive-behavior therapy consistently produces clinically significant reductions (from 4 8 % to 9 8 % ) in binge eating (Marcus et al., 1996; Smith, Marcus, &c Kaye, 1992; Telch, Agras, Rossiter, Wilfley, & Kenardy, 1990; WUfley & Cohen, 1997; Wilfley et al., 1993). A n important extension of cognitive-behavior therapy was pioneered by Carter and Fairburn (1998), w h o assessed its effectiveness in a 12-week program w h e n delivered with little or n o professional attention. In this study, patients with binge-eating disorder were given Fairburn's (1995) book Overcoming Binge Eating. Then they either were given instructions to read and apply the contents (pure self-help), or received six to eight 25-minute sessions with a nonprofessional "facUitator." The results were comparable to those of faceto-face treatments, with reductions in the frequency of binge eating of 5 3 % in the pure selfhelp condition and 7 6 % in the guided self-help condition. A second psychological treatment (also following the precedent with bulimia nervosa) is interpersonal therapy, modified by Wilfley and colleagues (1993) for application to binge-eating disorder. It too produced a cUnically significant reduction ( 7 1 % ) in binge eating, with maintenance of these effects at a 1-year follow-up (Wilfley et al., 1993, 2000). It is worthy to note that, despite the reduction in binge eating, neither cognitive-behav-
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ior therapy nor interpersonal therapy for binge-eating disorder has produced significant weight loss. There are two possible explanations of this surprising finding. First, the excess caloric intake of the binges m a y be so small as to m a k e negligible or n o contribution to body weight. Second, nutrient intake that would have been consumed in binges m a y be redistributed to the non-binge-eating caloric intake. Pharmacotherapy Pharmacotherapy has also reduced the frequency of binge eating. The first controlled trial (Alger, Schwalberg, Bigaoutte, Michalek, & H o w a r d , 1991) found that, compared to a placebo control, neither naltrexone nor imipramine reduced the frequency of binges. H o w ever, a significant reduction in bingeing was found in small, short-term trials of three antidepressants—desipramine ( M c C a n n & Agras, 1990), fluvoxamine (Hudson et al., 1998) and sertraline (McElroy et al., 2000)—and in one trial of the appetite suppressant dexfenfluramine (Stunkard, Berkowitz, Tanrikut, et al., 1996). T w o of the studies reported weight loss (Hudson et al., 1998; McElroy et al., 2000), but two did not ( M c C a n n & Agras, 1990; Stunkard, Berkowitz, Tanrikut, et al., 1996). In the latter two studies, the efficacy of the drugs was shown by the prompt recurrence of bingeing w h e n medication was discontinued ( M c C a n n &c Agras, 1990; Stunkard, Berkowitz, Tanrikut, et al., 1996). Presumably medication could be used over the long term, but such use has never been attempted. Standard Weight Reduction Programs A surprising finding has been the effectiveness of traditional behavioral weight loss programs that ignore the issue of binge eating. Agras and colleagues (1994) found that such programs reduced binge eating as adequately as pharmacotherapy did, and Marcus, Wing, and Fairburn (1995) found that a behavioral weight loss program reduced the number of binge days from 21.6 per 28 days to 2.7 per 28 days. Four previous reports on the use of very-low-calorie diets together with behavioral treatment found that the presence of binge eating did not affect weight loss, adherence to diet, or attrition, and that the frequency of binge eating decreased (Laporte, 1992; Telch & Agras, 1993; W a d d e n , Foster, & Letizia, 1992; W a d d e n et al., 1994). H o , Nichaman, Taylor, Lee, and Foreyt (1995) have shown that those with binge eating were actually only half as likely as those without it to drop out of a large treatment program for obesity. Assessing the outcome of a behavioral treatment that also included no special provision for binge eating, Gladis and colleagues (1998) found that patients with binge-eating disorder lost significantly more weight than those without the disorder, and had comparable attrition rates and decreases in depression. The table in Porzelius, Houston, Smith, Arfkin, and Fisher (1995) shows that a standard behavioral treatment was as effecrive as a "binge-eating weight loss treatment" in reducing bingeing and body weight in persons with moderate and severe binge-eating disorder. These studies have clearly laid to rest one of the concerns that had motivated the development of cognitive-behavior therapy—namely, that dietary restriction might exacerbate problems with binge eating. It should be noted that few studies have addressed the longterm effects of behavioral treatment on binge eating; the limited effects on weight loss are all too well known. Binge-Eating Disorder: A Reassessment The surprising effectiveness of programs that have ignored the issue of binge eating calls for a reassessment of the nature of binge-eating disorder. In this reassessment, two types of studies are useful: those of placebo responsiveness and those of untreated subjects.
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Thefirsttype of research concerns the remarkable placebo responsiveness of bingeeating disorder. In the study by Alger and colleagues (1991) described above, placebo responsiveness was 6 8 % , not significantly less than the 7 9 % and 8 8 % reductions produced by active medication. In the H u d s o n and colleagues (1998) study, a m o n g patients receiving placebo, binges per week fell 4 1 % (from 5.3 * 2.5 to 3.1 ± 3.0; J. I. Hudson, personal communication), and 4 4 % of these patients showed a greater than 5 0 % reduction in binges per week. This placebo response was also sufficient to affect the results: A difference between fluvoxamine and placebo w a s statistically significant only in a completer analysis, not in a last-observation-carried-forward analysis. Similarly, in the McElroy and colleagues (2000) study, a m o n g patients receiving placebo, binges per week fell 4 6 % (from 7.2 ± 5.8 to 3.9 ± 3.8) (S. L. McElroy, personal communication). Once again, the placebo response was large enough to affect the results: T h e difference between sertraline and placebo was statistically significant only in a last-observation-carried-forward analysis, not in a completer analysis. A fourth study assessed placebo responsiveness by means of a 4-week placebo run-in period. During this period, binges fell from 6.0 to 1.8 per w e e k — a reduction of 7 0 % (Stunkard, Berkowitz, Tanrikut, et al., 1996). Figure 6.1 Ulustrates thefindings.But the placebo responsiveness was as great as any in the medical literature. The second kind of study assessed the fate of binge-eating disorder a m o n g persons w h o received no treatment at all, either as waiting-list control subjects or as members of a community survey. The shortest such duration was the 12 weeks of the minimal-treatment program of Carter and Fairburn (1998). A m o n g subjects in the waiting-hst control group, binge eating fell by 3 8 % . In the second longest period with no treatment, the 6-month community survey of Cachelin and colleagues (1997), partial remission was reported in 4 8 % of persons w h o had been diagnosed with binge-eating disorder. In a second community study, Fairburn, Cooper, D o U , N o r m a n , and O'Connor (in press) reported that only 1 0 % of sub-
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FIGURE 6.1. T w o illustrations of the unstable nature of binge-eating disorder. The panel on the left shows the 9 0 % decline in persons diagnosed as having binge-eating disorder during a 5-year period when they received no treatment. The panel on the right shows the 7 0 % decline in the frequency of binge eating during a 4-week period when subjects received only placebo. Data from Stunkard, Berkowitz, Tanrikut, Reiss, and Young (1996).
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jects diagnosed with binge-eating disorder at the beginning of the survey received this diagnosis 5 years later. Fairburn and colleagues (in press) concluded that, unlike bulimia nervosa, binge-eating disorder "is an unstable state with a strong tendency toward spontaneous remission." These two types of studies help to explain the results with binge-eating disorder of traditional weight loss programs that have ignored binge eating. These studies and their results raise serious doubt that control of binge eating is necessary before obese persons can lose weight, and that attempts at weight loss should be deferred until binge eating is controlled. In fact, it has been argued that "standard behavioral treatments are better able to address aU of the treatment needs of this [binge-eating] group" (Gladis et al., 1998, p. 383). If binge-eating disorder is an unstable state with a strong tendency toward spontaneous remission, should it be the object of special treatment? Probably not for the binge eating. Traditional weight loss programs appear fully able to cope with both the overweight and the binge eating of persons with this disorder. T h e diagnosis of binge-eating disorder, however, m a y serve another function: identification of persons whose comorbidity deserves treatment. Such treatment, however, should be directed toward the specific comorbid conditions, not toward the binge eating. In the last analysis, this m a y be the major value of the diagnosis of binge-eating disorder—as a marker for other psychological problems that deserve consideration in their o w n right.
NIGHT-EATING
SYNDROME
Whereas binge-eating disorder is the oldest of the eating disorders, the night-eating syndrome is the youngest. It was described for the first time in 1955 as a syndrome comprising the triad of morning anorexia, evening hyperphagia, and insomnia (Stunkard, Grace, & Wolff, 1955). Although this was not a defining characteristic, the disorder included depression with an unusual circadian pattern: The depression was minimal in the morning and increased during the evening and night. Clinical investigation revealed that it occurred disproportionately a m o n g obese persons during periods of life stress and was alleviated with the alleviation of the stress. In the 1955 publication, the night-eating syndrome was suggested to be a special diurnal response to stress characteristic of some obese persons. Although it has not been included in any edition of the D S M , studies of the prevalence of the night-eating syndrome have revealed that it is u n c o m m o n in the general population (1.5%; Rand, Macgregor, & Stunkard, 1997). Like that of binge-eating disorder, prevalence of the night-eating syndrome increases with increasing weight—to 8 . 9 % in an obesity clinic (Stunkard, 1959), and to a peak of 2 7 % a m o n g obese persons in a clinic for the surgical treatment of obesity (Rand et al., 1997). M u c h of what w e k n o w about the night-eating syndrome was reported by Birketvedt and coUeagues (1999). This study confirmed the elements of the night-eating syndrome previously reported, including night eating, evening hyperphagia, and insomnia. The list of provisional criteria for the syndrome developed by these authors is provided in Table 6.2. Birketvedt and coUeagues (1999) also quantified the evening hyperphagia, showing that daily food intake, which continued later than that of obese control subjects, was 2,930 kUocalories (kcal) compared to 2,334 for the control subjects (p < .055). Figure 6.2 shows that the cumulative caloric intake of the night-eating subjects lagged behind that of the obese control subjects so that at 6:00 P.M. they had consumed only 3 7 % of theh daily intake, compared to 7 4 % for the controls (p < .001). The food intake of the control subjects then slowed, while that of the night-eating subjects conrinued at a rapid pace untU after midnight. During the period from 10:00 p.m. to 6:00 a.m., the night-earing subjects consumed
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Binge-Eating Disorder and the Night-Eating Syndrome T A B L E 6.2. Provisional Criteria for the Night-Eating Syndrome
A. Morning anorexia, even if the subject eats breakfast B. Evening hyperphagia. At least 5 0 % of the daily caloric intake is consumed in snacks after the last evening meal C. Awakenings at least once a night at least three nights a week D. Consumption of high calorie snacks during the awakenings on frequent occasions E. The pattern occurs for a period of at least 3 months F. Subjects do not meet criteria for any other eating disorders Note. From Birketvedt et al. (1999). Copyright 1999 by the American Medical Association. Reprinted by permission.
5 6 % of their caloric intake, compared to 1 5 % for the control subjects (p < .001). A s reported also in the Stunkard and colleagues (1955) paper. Figure 6.2 shows that the m o o d of the night-eating subjects w a s lower than that of the control subjects during the morning, and that it fell significantly during the evening and night. T h e night-eating subjects studied by Birketvedt and colleagues (1999) suffered from both sleep onset and sleep maintenance insomnia, awakening 3.6 times per night, compared to 0.3 for the control subjects (p < .001). Half of the 178 awakenings of the night-eating subjects were associated with food intake, while none of the controls ate while they were
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I I I I I I I I I I I ' I I I I I I I ' I ' I I 06 08 10 12 14 16 18 20 22 24 02 04 Time FIGURE 6.2. Twenty-four-hour pattern of mean cumulative energy intake and mood ^r a 5-day period. The intake of the night-eating subjects lags behind that of control subjects untU 10:00 p.m. and then greatly exceeds it (p < .001). Daytime m o o d of the night-eatmg subjects is ower than that of the control subjects (p < .001) and falls even lower during the evemng and night (p < .001). Error bars represent S E M in all figures. N E S indicates night-eating syndrome. From Birketvedt et al. (1999). Copyright 1999 by the American Medical Association. Reprinted by permission.
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awake. The nighttime snacks of the night-eating subjects were not binges but of only moderate size, averaging 271 kcal. The carbohydrate content of these nighttime snacks was very high ( 7 0 % of caloric intake), compared to 4 7 % for their food intake during the rest of the day (p < .001). Furthermore, the carbohydrate-to-protein rario of the nightrime snacks was also very high—7:1. This nutrient pattern of a high carbohydrate-to-protein ratio increases the availability of tryptophan for transport into the brain and conversion into serotonin with its sleep-promoting properties (Berry, G r o w d o n , W u r t m a n , Caballero, & Wurtman, 1991; Yokogoshi & W u r t m a n , 1986). This sequence makes h appear that the nighttime snacks are a form of self-medication for insomnia. The behavioral study was complemented by a neuroendocrine study conducted in the Clinical Research Center of the University Hospital in Tromso, N o r w a y , where subjects were admitted for 24-hour periods (Birketvedt et al., 1999). All subjects were w o m e n , and both the night-eating and control groups included both overweight and normal-weight subjects, matched for body mass index and age. Unlike the usual nighttime eating of the nighteating subjects, all subjects received four meals of 4 0 0 kcal at 8:00 a.m., 12:00 noon, 4:00 P.M., and 8:00 p.m. A m o n g the night-eating subjects, both overweight and normal-weight, there was a marked blunting of plasma melatonin levels at night (p < .001). A s expected, plasma leptin levels were considerably higher a m o n g overweight subjects than a m o n g normal-weight ones in both groups. In contrast to the expected rise in leptin at night a m o n g the control subjects, there was no increase in leptin a m o n g the night-eating subjects, either overweight or normal-weight. Confirming the earlier clinical impression that the night-eating syndrome was associated with stress, plasma Cortisol levels of the night-eating subjects were higher than those of control subjects for most of the 24 hours (see Figure 6.3). The night-eating syndrome appears to be a unique combination of an eating disorder, a sleep disorder, and a m o o d disorder. The distinctive neuroendocrine findings are closely associated in a pattern that helps to link these findings with the behavior characteristic of this syndrome. Thus the blunting of the nighttime rise in melatonin m a y contribute to the sleep maintenance insomnia, as suggested by Hajak and colleagues (1995), and to depression, as suggested by Kennedy, Garfinkel, Parienti, Costa, and Braun (1989). The failure of leptin to rise at night must limit its usual nighttime suppression of appetite and m a y permit the breakthrough of hunger impulses, further disrupting sleep. The elevated levels of Cortisol reflect the clinical impression that night eating occurs during periods of life stress. The first step in defining a disease or disorder has been taken in the case of the nighteating syndrome: It is readily recognized by persons manifesting the disorder, and physicians are becoming familiar with it. There have been no studies of treatment to date, but research on this topic is currently underway. The nature of the symptoms suggests the use of melatonin and selective serotonin reuptake inhibitors. The night-eating syndrome appears to differ from binge-earing disorder both in the far greater frequency of nighttime awakenings and in the modest amount of the food ingested—270 kcal, compared to the 1,300 kcal ingested during eating binges reported by Grilo and Schiffman (1994). It appears to differ also from the "nocturnal sleep-related eating disorders" reported in sleep research clinics and characterized by earing upon awakening from sleep, often in association with sleepwalking and related sleep disturbances. The relation between these disorders and the night-eating syndrome is unclear, in part because of the uncertainty regarding the nature of the former disorders. Thus Schenk and M a h o w a l d (1994) reported only 38 (0.5%) cases out of approximately 8,000 polysomnographk examinations, and in 8 4 % the night eating occurred during total or partial unconsciousness. Manni, Ratti, and Tartara (1997), on the other hand, reported
Binge-Eating Disorder and the Night-Eating Syndrome 900 -1
117
control NES
800 700 600 i 500 c o in e 400 o 300 u 200 100 —r08
—r12
ia
— I — 20 Time
-~r24
—r— 04
—r— 08
Figure 6.3. Twenty-four-hour mean plasma Cortisol levels in subjects with (n = 12) and without (n = 21) night-eating syndrome (NES). The asterisk and line indicate a significant difference between the levels of the two groups (p < .001). From Birketvedt et al. (1999). Copyright 1999 by the American Medical Association. Reprinted by permission.
that 5 . 8 % of 120 persons referred for insomnia manifested night eating during full consciousness.
SUMMARY A N D CONCLUSIONS The identification of two different eating disorders helps to define two subsets of obese persons w h o m a y benefit from special attention. Studies of binge-eating disorder s h o w that traditional behavioral weight reduction programs reduce binge eating and body weight and are the treatment of choice. T h e diagnosis of binge-eating disorder m a y be m o s t useful as a marker for the other psychological problems that frequently affect those w h o binge-eat, and that deserve treatment in their o w n right. Identification of the night-eating syndrome provides information that m a y be useful in the care of persons afflicted with this disorder. Treatment of the night-eating syndrome has not been assessed since the initial report (Stunkard et al., 1955). In that report, h w a s noted that long-term psychodynamic psychotherapy w a s associated with improvement in the night eating behaviors of s o m e patients. Anecdotal reports from persons with night-eating syndrome w h o have explored treatment options suggest that selective serotonin reuptake inhibitors have been helpful, as might be expected from their effects o n disturbances in m o o d and sleep. In view of the lack of rise in nighttime melatonin, provision of such agents at bedtime w o u l d seem a rational option.
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Gladis, M. M., Wadden, T. A., Vogt, R., Foster, G., Kuehnel, R. H., & Bartktt, S. J. (1998). Behavioral treatment of obese binge eaters: D o they need different care? Journal of Psychosomatic Research, 44, 375-384. Gorman, B. S., Sc Allison, D. B. (1995). Measures of restrained eating. In D. B. AUison (Ed.), History of assessment methods for eating behavior and weight related problems. Thousand Oaks, CA: Sage. Grilo, C. M., Sc Masheb, R. M . (2000). Onset of dieting vs. binge eating in outpatients with binge eating disorder. International Journal of Obesity, 24, 4 0 4 ^ 0 9 . Grilo, C. M., Si Shiffman, S. (1994). Longitudinal investigation of the abstinence violation effect in binge eaters. Journal of Consulting and Clinical Psychology, 62, 611-619. Hajak, G., Rodenbeck, A., Staedt, J., Bandelow, B., Huether, G., & Rather, E. (1995). Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia. Journal of Pineal Research, 19, 116-122. Herman, C. P., & Polivy, J. (1980). Restrained eating. In A. J. Stunkard (Ed.), Obesity (pp. 208-225). Philadelphia: W.B. Saunders. Herman, C. P., & Polivy, J. (1990). From dietary restraint to binge eating: Attaching causes to effects. Appetite, 14, 123-125. Ho, K. S. I., Nichaman, M . Z., Taylor, W . C , Lee, E. S., & Foreyt, J. P. (1995). Binge eating disorder, retention and drop-out rate in an adult obesity program. International Journal of Eating Disorders, 18,291-194. Hudson, J. I., McElroy, S. L., Raymond, N . C , Crow, S., Keck, P. E., Carter, W . P., MitcheU, J. E., Strakowski, S. M., Pope, H . G., Coleman, B. S., & Jeffrey, J. M . (1998). Fluvoxamine in the treatment of binge eating disorder: A multicenter placebo-controlled, double-blind trial. American Journal of Psychiatry, 155, 1756-1762 Kennedy, S. H., Garfinkel, P. E., Parienti, V., Costa, D., & Braun, G. M . (1989). Changes in melatonin levels but not Cortisol levels are associated with depression in patients with depression and eating disorders. Archives of General Psychiatry, 46, 73-78. Kuehnel, R. H., & Wadden, T, A. (1994). Binge eating disorder, weight cycling, and psychopathology. International Journal of Eating Disorders, 15, 321-329. Laporte, D. J. (1992). Treatment response in obese binge eaters: Preliminary results using a very low calorie diet ( V L C D ) and behavior therapy. Addictive Behaviors, 17, 247-157. Manni, R., Ratti, M . T., & Tartara, A. (1997). Nocturnal eating: prevalence and features in 120 insomniac referrals. Sleep, 20, 734-738. Marcus, M . D. (1997). Adapting treatment for patients with binge-eating disorder. In D. M . Garner Si P. E. Garfinkel (Eds.), Handbook of treatment for eating disorders (2nd ed., pp. 484-493). N e w York: Guilford Press. Marcus, M . D., Amith, D., Santelh, R., Si Kaye, W . (1992). Characterization of eating disordered behavior in obese binge eaters. International Journal of Eating Disorders, 12, 249-255. Marcus, M . D., Wing, R. R., Ewing, L., Kern, E., Gooding, W., Si McDermott, M . (1996). Psychiatric disorders among obese binge eaters. International Journal of Eating Disorders, 9, 69-77. Marcus, M . D., Wing, R. R., & Fairburn, C. G. (1995). Cognitive behavioral treatment of binge eating vs. behavioral weight control on the treatment of binge eating disorder. Annals of Behavioral Medicine, 17, S090. Marcus, M . D., Wing, R. R., Si Hopkins, J. (1988). Obese binge eaters: Affect, cognitions and response to behavioral weight control. Journal of Consulting and Clinical Psychology, 56, 433-439. Marcus, M . D., Wing, R. R., Sc Lamporski, D. M . (1985). Binge eating and dietary restraint in obese patients. Addictive Behaviors, 10, 163-168. McCann, U. D., & Agras, W . S. (1990). Successful treatment of nonpurging bulimia nervosa with desipramine: A double-blind, placebo-controlled study [see comments]. American Journal of Psychiatry, 147, 1509-1513. McElroy, S. L., Casuto, L., Nelson, E., Lake, K. A., SoutuUo, C , Keck, P., Sc Hudson, J. I. (2000). Sertraline in the treatment of binge eating disorder: A randomized trial. American Journal of Psychiatry, 157(6), 1004-1006.
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Mitchell, J. E., Sc Mussell, M. P. (1995). Comorbidity and binge eating disorder. Addictive Behavio 20, 725-732. MusseU, M . P., Mitchell, J. E., Fenna, C. J., Crosby, R. D., Miller, J. P., & Hoberman, H. M . (1997). A comparison of onset of binge eating versus dieting in the development of bulimia nervosa. International Journal of Eating Disorders, 12, 353-360. Polivy, J., & Herman, C. P. (1985). Dieting and bingeing: A causal analysis. American Psychologist, 40, 193-201. Polivy, J., Si Herman, C. P. (1993). Etiology of binge eating: Psychological mechanisms. In C. G. Fairburn Si G. T. Wilson (Eds.), Binge eating: Nature, assessment, and treatment (pp. 173-205). N e w York: Guilford Press. Polivy, J., Herman, C , Olmsted, M., Si Jazwinski, C. (1984). Restraint and binge eating. In R. C. Hawkins, W . J. Erenow, Si P. P. Clement (Eds.), The binge-purge syndrome: Diagnosis, treatment and research (pp. 104-122). N e w York: Springer. Porzelius, L. K., Houston, C , Smith, M., Arfkin, C , Si Fisher, E. (1995). Comparison of a standard behavioral weight loss treatment and a binge eating weight loss treatment. Behavior Therapy, 26, 119-134. Rand, C. S. W., Macgregor, M . D., Sc Stunkard, A. (1997). The night eating syndrome in the general population and among post-operative obesity surgery patients. International Journal of Eating Disorders, 22, 65-69. Schenk, C. H., & Mahowald, M . W . (1994). Review of nocturnal sleep-related eating disorders. International Journal of Eating Disorders, 16, 343-356. Smith, D. E., Marcus, M . D., Sc Kaye, W . (1992). Cognitive-behavioral treatment of obese binge eaters. International Journal of Eating Disorders, 12,157-161. Spitzer, R. L., Devlin, M., Walsh, B. T., Hasin, D., Wing, R., Marcus, M., Stunkard, A. J., Wadden, T., Yanovski, S., Agras, S., MitcheU, J., Sc Nonas, C. (1992). Binge eating disorder: A multisite field trial of the diagnostic criteria. International Journal of Eating Disorders, 11, 191-203. Spitzer, R. L., Stunkard, A. J., Yanovski, S., Marcus, M . D., Wadden, T. A., & Wing, R. R. (1993). Binge-eating disorder should be included in DSM-IV: A reply to Fairburn et al.'s "The classification of recurrent overeating: The 'binge-eating disorder' proposal." International Journal of Eating Disorders, 13, 161-169. Spitzer, R. L., Yanovski, S., Wadden, T. A., Wing, R., Marcus, M . D., Stunkard, A. J., Devlin, M., MitcheU, J., Hasin, D., & H o m e , R. L. (1993). Binge-eating disorder: Its further validation in a multisite study. International Journal of Eating Disorders, 13, 137-150. SpurreU, E. B., WUfley, D. E., Tanofsky, M . B., & BrowneU, K. D. (1997). Age of onset for binge eating disorder: Are there different pathways to binge eating? International Journal of Eating Disorders, 21, 55-65. Stunkard, A. J. (1959). Eating patterns and obesity. Psychiatric Quarterly, 33, 284-294. Stunkard, A. J. (1993). A history of binge eating. In C. G. Fahburn & G. T. Wilson (Eds.), Binge eating: Nature, assessment, and treatment (pp. 15-34). N e w York: Guilford Press. Stunkard, A. J., Berkowitz, R., Tanrikut, C , Reiss, E., &; Young, L. (1996). D-Fenfluramine treatment of binge eating disorder. American Journal of Psvchiatrv, 153, 1455-1459. Stunkard, A. J., Berkowitz, R., Wadden, T., Tantikut, C , Reiss, E., &; Young, L. (1996). Binge eating disorder and the night eating syndrome. International Journal of Obesity, 20, 1-6. Stunkard, A. J., Grace, W . J., Si Wolff, H. G. (1955). The night-eating syndrome: A pattern of food intake among certain obese patients. American Journal of Medicine, 19, 78-86. Stunkard, A. J., & Messick, S. (1985). The Three-Factor Eating Questionnaire to measure dietary restraint, disinhibition and hunger. Journal of Psvchosomatic Research, 29, 71-83. Tanofsky, M . B., Wilfley, D. E., Spurrell, E. B., Welch, R., & BrowneU, K. D. (1997). Comparison of men and w o m e n with binge eating disorder. International Journal of Eating Disorders, 21, 49-54. Telch, C. F., Si Agras, W . S. (1993). The effects of a very low calorie diet on binge eating. Behavior Therapy, 24, 177-193. Telch, C. F., Agras, W . S., Si Rossiter, F. M . (1988). Binge eating increases with increasing adiposity. International Journal of Eating Disorders, 7, 115-119.
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Telch, C. F., Agras, W. S., Rossiter, F. M., Wilfley, D. E., Si Kenardy, J. (1990). Group cognitive behavioral treatment for non-purging bulimics: A n initial evaluation. Journal of Consulting and Clinical Psychology, 58, 629-635. Wadden, T. A., Foster, G. D., & Letizia, K. A. (1992). Response of obese binge eaters to treatment by behavior therapy combined with very low calorie diet. Journal of Consulting and Clinical Psychology, 60, 808-811. Wadden, T. A., Foster, G. D., & Letizia, K. A. (1994). One-year behavioral treatment of obesity: Comparison of moderate and severe caloric restriction and the effects of weight maintenance therapy. Journal of Consulting and Clinical Psychology, 62, 165-171. Westenhoefer, J., Stunkard, A. J., & Pudel, V. (1999). Validation offlexibleand rigid control dimensions of dietary restraint. International Journal of Eating Disorders, 26, 53-64. Wilfley, D. E., Agras, W . S., Telch, C. F., Rossiter, E. M., Schneider, J. A., C o k , A. G., Sifford, L., Si Raeburn, S. D. (1993). Group cognitive-behavioral therapy and group interpersonal psychotherapy for the nonpurging bulimic individual: A controlled comparison. Journal of Consulting and Clinical Psychology, 61, 296-305. Wilfley, D. E., & Cohen, L. R. (1997). Psychological treatment of bulimia nervosa and binge eating disorder. Psychopharmacology Bulletin, 33, 4 3 7 ^ 5 4 . Wilfley, D. E., Schwartz, M . H., SpurreU, E. B., & Fahburn, C. G. (2000). Using the Eating Disorders Examination to identify specific psychopathology of binge eating disorder. International Journal of Eating Disorders, 27, 259-269. Wilson, G. T., Nonas, C. A., & Rosenblum, G. D. (1993). Assessment of binge eating in obese patients. International Journal of Eating Disorders, 150, 1472-1479. Yanovski, S. Z. (1993). Binge eating disorder: Current knowledge. Obesity Research, 1, 306-324. Yanovski, S. Z., Nelson, J. E., Dubbert, B. K., & Spitzer, R. L. (1993). Association of binge eating disorder and psychiatric comorbidity in obese subjects. American Journal of Psychiatry, 150, 1472-1479. Yanovski, S. Z., & Sebring, N . G. (1994). Recorded food intake of obese w o m e n with binge eating disorder before and after weight loss. International Journal of Eating Disorders, 15, 135-150. Yokogoshi, H., & Wurtman, R. J. (1986). Meal composition and plasma amino acid ratios: Effects of various proteins or carbohydrates, and of various protein concentrations. Metabolism, 35, 637-642.
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P A R T 11
HEALTH CONSEQUENCES O F
W E I G H T
R E D U C T I O N
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7
T h e
Relationship
Intentional Disease
W e i g h t
Incidence
of
Loss
a n d
to
Mortality
EDWARD W. GREGG DAVID F. W I L L I A M S O N
Obesity is related to m a n y adverse health outcomes, including cardiovascular disease (CVD), diabetes, cancer, osteoarthriris, sleep apnea, and mortahty (National Institutes of Health Consensus Development Panel on the Health Imphcations of Obesity, 1985; Pi-Sunyer, 1993a). Weight loss, on the other hand, is k n o w n to improve physiological risk factors such as impaired glucose tolerance (IGT), hyperlipidemia, and high blood pressure over the short term (Maggio & Pi-Sunyer, 1997; Pi-Sunyer, 1993b). Despite these benefits, epidemiological studies have generally failed to show that weight loss reduces disease incidence or mortality, but have instead suggested that the greatest longevity results from stable weight or slight weight gain (Andres, Muller, & Sorkin, 1993; Lee & Paffenbarger, 1996). Others have suggested that repeated weight loss and regain m a y actually be detrimental (Blair, Shaten, BrowneU, Collins, & Lissner, 1993; H a m m , Shekelle, & Stamler, 1989; Lissner et al., 1991). Thus a quandary exists: It is clear that obesity is bad, but do w e k n o w whether intentional weight loss is good? The contradictory reports of the effects of weight loss m a y stem from the fact that there are m a n y different circumstances of weight loss. For instance, weight loss m a y be deliberate or intentional, as achieved through lifestyle or medical interventions. Weight loss m a y also be unintentional, but resulting from a deliberate process to improve health, such as through physical activity or dietary change. Finally, weight loss m a y occur unintentionally due to k n o w n disease processes, mental illness, stressful life events, aging, or u n k n o w n circumstances. Estimates from epidemiological studies suggest that unintentional weight loss is almost as c o m m o n as intentional weight loss (WiUiamson, 1997). National estimates have s h o w n that a m o n g those reporting weight loss, about 6 0 % lost the weight intentionally and 4 0 % unintentionally (Meltzer & Everhart, 1995). Obesity has become increasingly prevalent and costly, affecting approximately onefourth of U.S. adults and leading to over $50 biUion in direct medical costs (Flegal, CarroU, 125
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Kuczmarski, & Johnson, 1998; Kuczmarski, Flegal, CampbeU, & Johnson, 1994; Wolf &c Colditz, 1996). Given that almost two-thirds of overweight people try to lose weight in any given year, and that approximately 4 0 % of them report initially succeeding (Meltzer &c Everhart, 1996), it is important to understand whether the short-term physiological benefits of weight loss really translate into long-term reductions in morbidity and mortality. In this chapter w e review the published literature of the effects of intentional weight loss on health outcomes, with particular emphasis on epidemiological studies and clinical trials of weight loss occurring intentionally or accompanying lifestyle-based interventions. As background, w e also briefly summarize the physiological effects of weight loss and the epidemiological studies that have assessed the effects of weight loss of u n k n o w n intent on mortality.
S U M M A R Y O F P H Y S I O L O G I C A L EFFECTS O F I N T E N T I O N A L W E I G H T L O S S Short-term intentional weight loss has been consistently related to physiological benefits that could improve overaU health (Figure 7.1). In brief, intentional weight loss has been related to improvements in blood pressure, low-density lipoprotein (LDL), total cholesterol, triglycerides, insulin levels, and cardiorespiratory fitness in both general populations and those with hypertension and C V D . It is also related to improved glycemic control among people with diabetes (Maggio & Pi-Sunyer, 1997; Pi-Sunyer, 1993b). Weight loss of 4 % - 8 % has been related to average reductions in systolic and diastolic blood pressure of 3-8 m m H g over 6-12 months (Agurs-CoUins, Kumanyika, Ten Have, & Adams-CampbeU, 1997; Eriksson &c Lindgarde, 1998; M c M a h o n , Cutler, Brittain, & Higgins, 1987; Torjeson et al., 1997; Trials of Hypertension Prevention [ T O H P ] Collaborative Group, 1992, 1997; Wing, Venditti, Jakicic, PoUey, & Lang, 1998; W o o d , Stefanick, Williams, & Haskell, 1991). Relative reductions in total and L D L cholesterol have typically been 5 % - 1 0 % ; such reductions m a y depend in part upon whether the weight loss is accompanied by reduced fat intake and increased physical activity (Andersen, W a d d e n , Bartlett, Vogt, & Weinstock, 1995; Dengel, Katzel, & Goldberg, 1995; Katzel et al., 1995; Stefanick et al., 1998; Torjeson et al, 1997; W o o d et al., 1991). Effects on high-density lipoprotein ( H D L ) cholesterol have been variable, with levels tending to decline with weight loss over the short term, but
Physical activity/diet
Potential positive Dhvsloloaical effects Blood pressure Lipid levels Glucose tolerance/insulin resistance Mobility Physical fitness
Potential positive outcomes iCHD i Stroke i Diabetes i Disability T Quality of life i Mortality
Potential negative Dhvsloloaical effects Loss of muscle m a s s Loss of bone mass Gallstone formation
Potential negative outcomes T Falls T Fractures i Quality of life t Mortality
Intentional weight loss
F I G U R E 7.1. M o d e l of potential pathways for influence of weight loss o n disease incidence and mortality.
Intentional Weight Loss and Disease Incidence/Mortality
127
returning to baseline levels or even increasing after longer-term weight stability (Andersen et al., 1995; Dengel et al., 1995; Pi-Sunyer, 1993b; Simkin-SUverman et al., 1995, 1998; Wing et al., 1998). A m o n g people with diabetes, loss of 5 % - 1 0 % of body weight has been related to net decreases in glycated hemoglobin of 1.0%-2.5% (Agurs-CoUins et al., 1997; W i n g et al., 1987,1988). Weight loss m a y also improve sleep apnea symptoms, pulmonary function, osteoarthritis symptoms, and mobility, but evidence from randomized controlled trials (RCTs) to support these effects is sparse (Pi-Sunyer, 1993b; Strobel &c Rosen, 1996). Notably, the strongest effects of weight loss on physiological parameters are observed in short-term studies. F e w studies have assessed the sustainability of weight-loss and its physiological effects over more than a year. Given the well-documented tendency for people w h o intentionally lose weight to regain it gradually over the following years (Wadden, 1993), it is possible that the initial improvements in risk factors resuhing from weight loss diminish over time as well. Potential negative consequences of intentional weight loss also exist and m a y depend upon the strategies used to achieve it. Acute cardiac arrest, cardiac arrhythmias, and electrolyte imbalances have been associated with extended use of very-low-calorie diets, particularly those providing fewer than 800 kilocalories (kcal)/day and inadequate protein content (Centers for Disease Control and Prevention, 1998; Pi-Sunyer, 1993b; W a d d e n , VanltaUie, 8c Blackburn, 1990). Similarly, cardiac valvulopathy and primary pulmonary hypertension have been associated with certain weight loss medications (Centers for Disease Control and Prevention, 1997). Intentional weight loss has also been related to gallstone formation a m o n g obese persons (Liddle, Goldstein, & Saxton, 1989; Weinsier, Wilson, & Lee, 1995). Intentional weight loss of at least 2.2 kg (i.e., 5 pounds) was associated with a 1 3 8 % increased risk of cholecystectomy, independent of initial body mass index (BMI), a m o n g w o m e n in the Nurses' Health Study (Syngal et al., 1999). In a review of studies evaluating weight-loss-associated gallstone formation, Weinsier and colleagues (1995) noted that this risk w a s greatest when the rate of weight loss exceeded 1.5 kg per week, leading the authors to recommend more gradual weight loss to avoid this complication. S o m e have suggested that repeated failed attempts at weight loss (e.g., weight cycling) have detrimental effects on metabolism, although objective reviews of this literature suggest otherwise (National Task Force on the Prevention and Treatment of Obesity, 1994; Wing, 1992). Weight loss m a y also include loss of lean mass, and at least one R C T (Salamone et al., 1999) found a greater rate of bone loss a m o n g premenopausal w o m e n enrolled in an 18-month weight loss intervention than a m o n g controls. A m o n g elderly persons, such effects could conceivably reduce muscle strength or physical functioning, and thus increase risk for falls and osteoporotic fractures.
EPIDEMIOLOGICAL STUDIES OF GENERAL WEIGHT LOSS
(INTENTION U N K N O W N ) Because of the physiological impact of weight loss, long-term weight reduction should not only reduce risk for m a n y chronic diseases (particularly diabetes and C V D ) , but also increase longevity. T h efirstepidemiological studies to assess weight loss and longevity came from the life insurance industry, wherein weight loss of unspecified intention a m o n g working-aged, overweight m e n w a s associated with 2 0 % - 3 0 % reductions in mortality (Dublin, 1953; Dublin & Marks, 1951). However, these studies lacked control for confounding by comorbidhies, and they m a y have been biased by medical screening that varied according to weight loss (Williamson &C P a m u k , 1993). S o m e subsequent epidemiological studies also
128
HEALTH C O N S E Q U E N C E S O F W E I G H T REDUCTION
found weight loss to be associated with reduced mortality (Hammond & Garfinkel, 1969), but as indicated by several extensive review articles, m a n y more studies have found weight loss to be associated with increased mortahty (Andres et al., 1993; Lee & Paffenbarger, 1996; Williamson & Pamuk, 1993). For example, Lee and Paffenbarger (1996) reported that only 3 out of 17 epidemiological studies found weight loss to be associated with increased longevity; mortality tended to be highest a m o n g people w h o had lost or gained substantial weight during their lives, and lowest a m o n g those whose weight had remained stable. The authors pointed out, however, that these studies are limited by lack of data on weight loss intention, and in some cases by failure to rule out coexisting disease or to control adequately for smoking and other behavioral confounders. T w o recent epidemiological studies, however, suggest that the association of weight loss and longevity depends on the composition of the weight that is lost. Allison and colleagues (1999) used skinfold thickness measures to estimate change in body fat in two population-based cohort studies (Framingham, Massachusetts, and Tecumseh, Michigan). A L though each additional standard deviation of weight loss (4.6 kg-7.6 kg in the two studies) was associated with a 2 8 % - 3 9 % increase in mortality rates, each additional standard deviation of fat loss was associated with about a 1 6 % reduction in mortality rates in the two studies. In support of the view that loss of body fat increases longevity, Heitmann, Erikson, EUsinger, Mikelsen, and Larsson (2000) followed up a cohort of 60-year-old Swedish men 2 2 years after their body composition had been measured by potassium counting. They found that m e n with lower lean body mass had increased mortality, but m e n with lower fat mass had decreased mortality. There m a y be reason to believe that weight loss could have either beneficial or detrimental effects on musculoskeletal outcomes, disability, and quality of life. In the Framingh a m Knee Osteoarthritis Study, weight loss during the previous 10 years was associated with a 5 9 % reduction in risk for symptomatic knee osteoarthritis a m o n g overweight w o m e n (Felson, Zhang, Anthony, Naimark, &c Anderson, 1992). Although obesity has also been related to an increased risk of disability (Launer, Harris, Rumpel & Madans, 1994), weight loss can result in loss of lean mass and bone mineral density, which could lead to adverse consequences, particularly a m o n g the elderly. This is evident in at least three cohort studies of older adults—the Study of Osteoporotic Fractures, the Established Populations for Epidemiologic Study of the Elderly, and the National Health and Examination Survey Follow-Up Study I—in which weight loss between middle age and later years was associated with at least a twofold increased relative risk of hip fracture and loss of mobility (Ensrud, Cauley, Lipshutz, & Cummings, 1997; Langlois et al., 1998; Launer et al., 1994). O n e population-based study has assessed the relationship between weight change and change in health-related quality of life. A m o n g w o m e n participating in the Nurses' Health Study, weight loss over 4 years was associated with improved physical function and vitality, particularly a m o n g the most obese w o m e n (Fine et al., 1999). The only exception was among lean w o m e n (BMI < 25 kg/m^), for w h o m weight loss was associated with worsening scores on physical functioning, freedom from bodily pain, vitality, and mental health. The authors conjectured that among the lean group in particular, weight loss was probably largely unintentional and a marker of physical or mental iUness.
METHODOLOGICAL LIMITATIONS OF THE EPIDEMIOLOGICAL STUDIES O F G E N E R A L W E I G H T L O S S A key limitation of the epidemiological hterature on general weight loss summarized above is the lack of information on weight loss intention (WUUamson, 1996). Several studies have
Intentional Weight Loss and Disease Incidence/Mortality
129
shown that in addition to being common, unintentional weight loss is associated with older age, negative health behaviors, and poor health status (French, Jeffery, Folsom, Williamson, & Byers, 1995; McGuire, Wing, & HiU, 2000; McGuire, Wing, Klem, & HiU, 1999; Meltzer & Everhart, 1995, 1996; W U U a m s o n et al., 1995). Weight loss m a y be related to depression or m a y be part of the natural history (particularly the end stages) of conditions such as cancer, diabetes, coronary heart disease, cerebrovascular disease, obstructive pulmonary disease, and dementia (Marton, Sox, & Krupp, 1981; T h o m p s o n & Morris, 1991). Thus inclusion of people w h o had unintentional weight loss in the studies discussed above could have spuriously increased disease incidence and mortality a m o n g those losing weight. Observational studies of weight loss and disease are plagued by other seemingly obvious, but confusing, methodological dilemmas. First, obese people, those w h o smoke, and those with preexisting disease are more likely to lose weight during their lives than healthy people w h o are of normal weight (French et al., 1995; Meltzer & Everhart, 1995). Thus the interpretation of studies relating weight loss to an increased risk of diseases such as diabetes and heart disease should acknowledge that people w h o lost weight were likely at higher risk for disease and death in thefirstplace. This points to the need for careful stratification and/or control for initial body weight and health status. For example, in a report from the Nurses' Health Study, a weight loss (intent unknown) of > 1 1 kg was related to an almost twofold increased risk of diabetes (Colditz, Willett, Rotnitzky, & Manson, 1995). After initial B M I was controUed for, however, weight loss was associated with about an 8 0 % reduced risk of diabetes. Second, people w h o lose weight are also more likely to experience weight cycling (French et al, 1995). Since some have argued that weight cycling m a y have its o w n adverse effects on metabolism and health outcomes independent of weight loss (National Task Force on the Prevention and Treatment of Obesity, 1994), weight cycling could also confound relationships between weight loss and disease. The reader is referred to several extensive reviews of the epidemiology of general weight loss and disease (Andres et al., 1993; Lee & Paffenbarger, 1996; WiUiamson, 1996; Williamson & P a m u k , 1993).
STUDIES O F I N T E N T I O N A L W E I G H T L O S S Because of the limhations of observational studies of general weight loss, we have focused the remainder of this review on studies in which weight loss intention was assessed directly or was part of controlled weight loss or lifestyle interventions. The limitations of observational studies point toward R C T s as an appropriate alternative to assessing the causal impact of intentional weight loss on health outcomes (Yanovski, Bain, & WiUiamson, 1999). However, with the exception of hypertension and diabetes studies, few R C T s have specifically examined the impact of weight loss approaches on morbidity or mortality. Thus evidence for evaluating whether a causal relationship between intentional weight loss and health outcomes comes from three types of studies: (1) observational cohort studies that include dhect self-report of weight loss intention; (2) nonrandomized controlled trials (NCTs) of weight loss interventions; and (3) R C T s of lifestyle interventions in which weight loss was a secondary objective.
Observational Cohort Studies Six prospective cohort studies and one retrospective cohort study have examined the relationship between intentional weight loss and mortality in middle-aged and older populations (Table 7.1).
T A B L E 7.1. S u m m a r y of Observational Cohort Studies Assessing Effects of Intentional Weight Loss on Disease Incidence and Mortality Author(s) Williamson etal. (1995)
Outcome Mortality
Design, mean follow-up Observational cohort, 13 yr
Population
Definition of weight loss
43,457 nonsmoking Self-reported U.S. white w o m e n intentional weight loss aged 40-64 yr
Weight change comparison Weight loss (0-9 kg and a 9 kg) vs. no change
Effect +
0
CO O
Effect of weight loss relative to control A m o n g w o m e n with obesity-related health conditions: 20 % L all-cause mortality; 4 0 % - 5 0 % -I obesity-related cancer mortality; 3 0 % - 4 0 % i diabetes mortality; no difference in C V D mortality. A m o n g healthy w o m e n : N o difference in all-cause, C V D , or diabetes mortality. 1-9 kg of intentional weight loss: 5 8 % t obesityrelated cancer mortality.
Self-reported weight loss with diet and exercise
Weight loss (10 lb) vs. no change
0 No difference in mortality among men or women.
Observational 9,228 Israeli m e n cohort, 18 yr aged 40-65 yr
Self-reported "slimming" diet for weight loss
Weight loss (>5 kg) vs. stable
- Twofold t mortality incidence.
Observational 49,337 overweight cohort, 13 yr U.S. m e n aged 40-64 yr
Self-reported intentional weight loss
Weight loss (0-9 kg and > 9 kg) vs. no change
0
Diehr et al. (1998)
Mortality
Observational cohort, 5 yr
Yaari Si Goldbourt (1998)
Mortality
Williamson et aL (1999)
Mortality
4,317 m e n and w o m e n aged >65yr
+
N o significant differences in all-cause, C V D , or cancer mortality. 3 3 % i diabetes-associated deaths among those with preexisting disease.
French et al. Mortality (1999)
Observational cohort with retrospective weight loss
25,897 Iowa w o m e n aged 55-69 yr
Weight loss Self-reported (>9 kg) vs. intentional weight no change loss (a 9 kg) between ages 18-39 yr, 40-54 yr, and >54yr
0
N o difference in all-cause or C V D mortality for any age group.
Ensrud et al. Hip fracture, (1997) falls
Observational cohort, 1.5 yr
6,754 white w o m e n aged >65yr
Self-reported intentional weight loss
Weight loss (10%) vs. no change
0 -
N o increased risk in fracture among those intentionally losing weight. 1 6 % t falling incidence.
Syngal et al. (1999)
Cholecystectomy
Observational cohort, 6 yr
47,153 w o m e n (mean age 55 yr)
Self-reported intentional weight loss
Weight loss (>5 lb)
-
13 8 % T cholecystectomy incidence.
Lean et al. (1994)
Diabetes incidence
Retrospective cohort, 9 yr
233 m e n and w o m e n with Type 2 diabetes (mean age 65 yr)
Dietary counseling from time of diabetes diagnosis
Each kilogram of weight loss
+
Each kg weight loss associated with 3 m o of increased survival (average survival = 8.8 yr).
+ 2 5 % - 2 8 % i in all-cause, C V D , and DM-related Loss vs. stable Self-reported 4,970 overweight mortality associated with intentional weight weight intentional weight m e n and w o m e n loss. Greatest reductions (33%) associated loss aged 40-64 yr with 1 0 % - 1 5 % weight loss. with diabetes "Effect refers to overall evidence of study for effect on mortality or disease incidence, with "+" referring to beneficial effect, "-" referrring to adverse effect, and " 0 " refering to no effect.
Williamson et al. (2000)
Mortality
Observational cohort, 12 yr
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HEALTH CONSEQUENCES OF WEIGHT REDUCTION
/Mortality In prospective studies of approximately 100,000 enrolled in the Cancer Prevention Study I, intentional weight loss w a s related to a 2 0 % reduction in aU-cause mortality and 3 0 % ^ 0 % reductions in diabetes and cancer mortality a m o n g w o m e n , as well as one-third reduction in diabetes-related mortality a m o n g m e n (WiUiamson et al., 1995, 2000). These reductions were greater for those w h o lost 1-9 kg than for those w h o lost more than 9 kg and were only observed a m o n g those with preexisting conditions such as heart disease, diabetes, and hypertension. However, there were no associations between intentional weight loss and C V D mortality in these studies. In a study specifically conducted a m o n g overweight diabetic persons in the Cancer Prevention Study, intentional weight loss w a s associated with about 2 5 % reduced risk of allcause, cardiovascular, and diabetes-related mortality (WiUiamson et al., 2000). Weight loss of up to 50 lbs was associated with reduced mortality, with greatest reductions observed a m o n g those losing 1 0 % - 1 5 % of initial weight. In contrast, intentional weight loss of >70 lbs and unintentional weight loss and weight gain are associated with small increases in mortality. A report of approximately 26,000 w o m e n aged 55-69 years in the Iowa Women's Health Study found that intentional weight loss of more than 9 kg during any of three periods of adulthood (ages 18-39, 40-54, or 55+ years) w a s unrelated to total C V D or aUcause mortality (French, Folsom, Jeffery, & WiUiamson, 1999). Those w h o had unintentionally lost more than 9 kg, however, were at 4 0 % - 6 0 % increased risk of C V D or all-cause mortality. O n e study has assessed intentional weight loss and mortality a m o n g older adults. In a 5-year follow-up of 5,204 adults aged 65 years or older enrolled in the Cardiovascular Health Study, the 5-year cumulative mortality a m o n g m e n with an intentional 4.4-kg (10pound) weight loss (16.4%) was equivalent to that for those with stable weight (16.1%), but mortality was over twice as high (33%) a m o n g those with an unintentional 4.4-kg weight loss (Diehr et al., 1998). A m o n g w o m e n , those with an intentional 4.4-kg weight loss had a slightly lower 5-year mortality incidence ( 5 % ) than those with stable weight (7.4%), and they had only one-third the mortality of those with unintentional weight loss (16.2%). Yaari and Goldbourt (1998) conducted an 18-year foUow-up of more than 9,000 Israeli m e n aged 40-65 years and found that, overall, weight loss of at least 5 kg was associated with a 2 0 % - 4 0 % greater risk of mortality than that associated with stable weight. The study also reported that, compared to m e n with stable weights, those w h o had lost at least 5 kg and reported being on a "slimming diet" to lose weight had a twofold higher mortality risk. However, these analyses based on dieting status did not control for body weight and important comorbidities such as hypertension and coronary heart disease, so it is unclear whether the increased mortality risk was due to underlying disease a m o n g those trying to lose weight. Thus, of the six prospective epidemiological studies that have assessed the relationship of intentional weight loss to mortality, one found benefits on all-cause, cancer, and diabetes mortaUty a m o n g w o m e n with preexisting disease (WiUiamson et al., 1995); one also found benefits on diabetes mortality a m o n g m e n (WiUiamson et al., 1999); and one found reduced C V D and all-cause mortality a m o n g m e n and w o m e n with diabetes (Williamson et al., 2000). Three studies found that intentional weight loss neither increased nor decreased allcause or C V D mortality a m o n g older aduh m e n (Diehr et al., 1998; French et al., 1999; Williamson et al., 1999); and one (Yaari & Goldbourt, 1998) found an increased risk of allcause mortality. Although these studies did not consistently find that intentional weight loss was associated with decreased mortality, they suggest that the earlier epidemiological stud-
Intentional Weight Loss and Disease Incidence/Mortality
133
ies relating weight loss of unknown intention to increased mortality were confounded by unintentional weight loss. O n e retrospective cohort study assessed mortality a m o n g 233 patients with Type 2 diabetes w h o had received intensive dietary counseling after their disease was diagnosed (Lean, Powrie, Anderson, &c Garthwaite, 1990). M e a n weight change was -3.5 kg in m e n and -2.3 kg in w o m e n . For the entire sample, life expectancy was 2.5 months longer for each kilogram of weight loss, and it was 3.6 months longer per kilogram of weight loss among those with a B M I greater than 25 kg/m^.
Osteoporotic Fractures Only one study has assessed the relationship of intentional weight loss to risk of musculoskeletal outcomes. A report by Ensrud and colleagues (1997) found that older w o m e n w h o had a 1 0 % unintentional weight loss had a significant 8 0 % increased risk of osteoporotic fracture, but those w h o lost weight intentionally did not have an increased fracture risk. Both intentional and unintentional weight loss were associated with slight but statistically significant (relative risk = 1.16-1.18) increased risks of falling, however.
NCTs of Weight Loss Interventions Several NCTs have examined the effects of weight loss on diabetes incidence and mortality (Table 7.2). Such trials are hampered by the fact that systematic differences in health status and behavior m a y exist between people w h o agree to undergo difficult weight loss interventions and those w h o do not.
Diabetes The M a l m o Prevention Trial (Eriksson & Lindgarde, 1991) recruited 785 m e n aged 47-49 years and enrolled them in a nonrandomized manner into four groups: (1) a 6-year diet and exercise intervention for people with IGT; (2) a usual-care condition for those with IGT; (3) the same diet-plus-exercise intervention conducted a m o n g people with diabetes; and (4) a control condition for persons with normal glucose tolerance. Percentages of B M I change a m o n g the I G T intervention, I G T control, diabetes, and normal glucose tolerance groups after 6 years were - 2 . 3 % , 0.5%, - 3 . 7 % , and 1.7%, respectively. Thus the I G T intervention group had a net 2 . 8 % B M I decrease (-2.3% vs. 0.5%), compared to the I G T control group. After 6 years, those with I G T in the intervenrion group had a 6 3 % reduction in diabetes incidence ( 1 1 % ) , compared to the nonrandomized control group of people with I G T ( 2 9 % ) . T w o studies found reduced incidence of diabetes a m o n g individuals w h o underwent surgical treatment for obesity. A study of 109 patients undergoing gastric bypass surgery (Long et al., 1994) and 2 7 nonrandomized controls found a strong protective effect of surgery on diabetes risk. The surgery group lost more than 5 0 % of excess weight after a year, and had only one incident case of diabetes a m o n g treated individuals (incidence = 0.15 per 100 person-years) after 6 years. By comparison, 6 out of the 2 7 control subjects (4.7 per 100 person-years) developed diabetes. A follow-up examination of the surgical patients reported 3 0 % loss of body weight after 7.6 years (Pories et al., 1995), and a m o n g those with diabetes, a reduction in diabetic medication use and overall mortaliry^ compared to those not receiving surgery (MacDonald et al., 1997). These studies, however, were limited by theh design, which included an unmatched and nonrandomized control group. In the Swedish Obese Subjects study, 845 individuals had bariatric surgery that w a s ac-
T A B L E 7.2. Summary of Nonrandomized Controlled Trials (NCTs) of Weight Loss Interventions: Effects on diabetes incidence and mortality
CO
Design, mean follow-up
Population
Definition of weight loss
Author(s)
Outcome
Eriksson & Lindgarde (1991)
Diabetes incidence
N C T , 6 yr
260 men aged 47-^9 yr with IGT
Long et al. (1994)
Diabetes incidence
N C T , 6 yr
136 men and women, 45 kg overweight, mean age 37 yr
N C T , 2 yr, 8yr
1,479 m e n and women, Bariatric surgery aged 37-60, B M I > 34 vs. control kg/m-^
Sjostrom et al.Diabetes (1999, 2000) incidence
Eriksson 8i Lindgarde (1998)
Mortality
N C T , 12 yr 423 men aged 47-49 yr with IGT
MacDonald et al. (1997)
Mortality
N C T , 9 yr
"See footnote to Table 7.1.
205 morbidly obese men and w o m e n (mean age 42 yr)
Diet and exercise mtervention vs. control Bariatric surgery vs. control
Diet and exercise intervention vs. control
Weight change comparison
Effect^
Effect of weight loss relative to control or referent group
2.3% loss vs. 0.5% gain (net 2.8%)
6 3 % L diabetes incidence.
> 50% of excess weight loss in year 1
30-fold t incidence of diabetes among controls compared to surgery group.
23% weight loss vs. no change
90% 4- diabetes incidence, and 62% i hypertension incidence; after 2 years 8 4 % -l diabetes incidence and no effect on hypertension after 8 years.
2.3% loss vs. 0.5% gain (net 2.8%) at 6 yr
51% i ischemic heart disease incidence, 5 5 % 4- all-cause mortality.
Bariatric surgery -30% weight loss at 10 years vs. control
4.5-foid t incidence of mortality among controls compared to surgery group.
Intentional Weight Loss and Disease Incidence/Mortalif/
135
companied by a 28-kg (23%) weight loss and impressive net reductions (compared to controls) in systolic blood pressure (7 m m H g ) , diastolic blood pressure (5 m m H g ) , triglycerides ( 2 7 % ) , glucose ( 2 3 % ) , total cholesterol ( 3 % ) , and H D L levels ( 1 1 % ) after the 2-year follow-up (Sjostrom, Lissner, Wedel, & Sjostrom, 1999). Cumulative (2-year) incidence of diabetes was only 0.2%, and hypertension incidence was 5 . 4 % a m o n g surgery patients, compared to a 6 % diabetes incidence and 1 4 % hypertension incidence a m o n g matched controls. This difference corresponded to 9 0 % and 6 2 % reductions in diabetes and hypertension risk, respectively, associated with the intervention. In a follow-up report after 8 years, the authors reported a continued reduction in diabetes incidence but not hypertension incidence associated with obesity surgery (Sjostrom, Peltonen, Wedel, and Sjostrom, 2000). A separate report from the same group showed that weight loss was significantly correlated (r = .36) with reductions in left ventricular mass and wall thickness a m o n g a subgroup of 63 patients losing weight through surgery or conventional means (Karason, Wallentin, Larsson, Sc Sjostrom, 1997).
Mortality A separate report from the previously described M a l m o Prevention Trial (Eriksson & Lindgarde, 1998) after 6 additional years of foUow-up (12 years total) showed that those with I G T assigned to the intervention group had about a 5 0 % reduction in ischemic heart disease mortality (3.6 per 1,000 person-years) and aU-cause mortality (6.5 per 1,000 person-years), compared to those in the I G T control group (7.3 ischemic heart disease deaths and 14.6 aU-cause deaths per 1,000 person-years). Mortality rates in the intervention group were equivalent to those in the group with normal glucose tolerance. However, the study did not report weight change after the second 6-year follow-up and was limited by the fact that differences in blood pressure existed at baseline (mean 138/92 m m H g for the intervention group vs. 144/97 m m H g for the control group).
RCT of Lifestyle Interventions At least three R C T s have studied the effects of weight loss interventions on hypertension incidence (Table 7.3). Other R C T s have studied the effects of lifestyle interventions accompanied by weight loss on incidence of diabetes, C V D , and mortality.
hlypertension In two studies, the T O H P CoUaborative Research Group (1992, 1997) tested the independent effects of modest weight loss and sodium on hypertension risk a m o n g 30- to 54-yearold m e n and w o m e n with high-normal diastolic blood pressure. In T O H P I, the weight loss intervention group achieved a 4 % weight loss and had a 3 4 % reduction in hypertension risk over 18 months. In T O H P II, the weight loss group achieved a m e a n 5 % weight loss over 6 months, but only 2 % after 3 years. Nevertheless, the weight loss group had a 2 1 % reduction in risk of hypertension after 4 years, compared to controls. A more recent R C T , the Trial of Nonpharmacological Interventions in the Elderly (Whelton et al., 1998), tested whether weight loss could be used to help obese hypertensive patients aged 60-80 years taper off their medication without having a cardiovascular event. Those randomly assigned to weight loss had a 3 0 % reduced incidence of the combined endpoint of hypertension, stroke, transient ischemic attack, congestive heart failure, or arrhythmia. However, this outcome was driven largely by hypertension, as the cumulative incidence of cardiovascular events w a s essentially equivalent between those in the weight loss
T A B L E 7.3. Summary of Randomized ControUed Trials (RCTs) of Lifestyle Interventions: Effects on Disease Incidence and Mortality Outcome
Author(s)
Population
Definition of weight loss
Weight change comparison Effect^
Effect of weight loss relative to control 3 4 % L hypertension incidence.
T O H P Collaborative Research Group (1992)
Hypertension incidence
R C T , 1.5 yr
2,182 m e n and w o m e n aged 30-54 yr with high-normal diastolic blood pressure
Diet and exercise intervention vs. control
Net 4 % loss vs. control
TOHP Collaborative Research Group (1997)
Hypertension incidence
R C T , 4 yr
2,382 overweight m e n Diet and exercise and w o m e n aged 30-54 intervention vs. control yr with high-normal diastolic blood pressure
Net 2 % loss vs. control at 3 yr
R C T , 2.5 yr
585 obese hypertensive m e n and w o m e n aged 60-80 yr
Diet and exercise Net 4 % loss vs. control intervention vs. control
3 0 % -l combined hypertension and C V D outcomes. 29%, 32%, and 33% 4- diabetes incidence in diet, exercise, and diet + exercise groups, respectively.
Whelton etal. (1998) Hypertension and C V D events _ OJ cs
Design, mean follow-up
+
2 1 % i- hypertension incidence.
Pan etal. (1997)
Diabetes incidence
R C T , 6 yr
577 m e n and w o m e n (mean age 45 yr) with IGT
Diet, exercise, andNet 2% weight loss among diet diet + exercise plus exercise; no interventions vs. weight change in control other groups
Wing etal (1998)
Diabetes incidence
R C T , 2 yr
154 m e n and w o m e n aged 40-55 yr
Diet, exercise, andNet 2% weight diet + exercise loss vs. control interventions vs. control
0
Cardioprotective diet intervention vs. control
+ 40% i cardiac events; 45% i total mortality; nonsignificant 5 1 % 4- stroke deaths.
Singh et al. (1992)
Cardiac events, mortality
R C T , 1 yr
406 m e n and w o m e n aged 50+ yr with coronary heart disease
Tuomilehto et al. (2001)
Diabetes incidence
R C T , 3.2 yr
522 overweight, glucose Diet and exercise intolerant men and vs. control w o m e n (mean age 55 ±7yr)
"See footnote to Table 7.1.
Net 6 % weight loss vs. control
Net 3.8% weight loss at 1 yr vs. control
+
N o significant association with diabetes incidence. 4.5-kg weight loss related to 3 0 % •[• diabetes incidence in post hoc analyses.
5 8 % i diabetes incidence.
Intentional Weight Loss and Disease Incidence/Mortalif/
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(14.3%) and usual-care (16.7%) conditions. At the end of the 2.5-year study, 39% of those in the weight loss intervention were medication- and event-free, compared to 2 6 % of those getting usual care.
Diabetes A study of 577 people with IGT randomly assigned to diet, exercise, or diet-plus-exercise groups in the D a Qing I G T and Diabetes Study in China resulted in 2 % - 5 % reductions in B M I and 2 9 % - 3 3 % reductions in diabetes incidence relative to controls over 6 years (Pan et al., 1997). Six-year cumulative incidence of diabetes ranged from 4 4 % to 4 7 % a m o n g lifestyle conditions, compared to 6 6 % a m o n g controls. However, these effects appeared to be independent of weight loss. Only overweight individuals in the diet plus exercise condition had lost weight (5.5% decrease in B M I ) compared to controls (3.2% decrease in B M I ) . Paradoxically, individuals w h o developed diabetes in the four groups had higher m e a n weight loss (0.9 kg) than those w h o did not develop diabetes (0.3 kg). It is possible, however, that in m a n y individuals weight loss occurred after being diagnosed with diabetes. W i n g and colleagues (1998) conducted a four-arm, 2-year intervention trial in which 154 individuals aged 40-55 years were randomly assigned to control, diet, exercise, or diet-plus- exercise groups. Relative to controls, the diet and diet-plus-exercise interventions achieved approximately 9 % weight loss after 6 months and 5 % - 7 % weight loss after 1 year. The initial 6-month weight loss was accompanied by significant improvements in several cardiovascular risk factors. However, after 2 years, the net weight loss a m o n g intervention groups w a s only 2 % ; most risk factor advantages had disappeared; and the incidence of diabetes was paradoxically higher (p = .08) in the intervention groups (diet, 3 0 % ; exercise, 1 4 % ; diet plus exercise, 1 6 % ) than in the control group ( 7 % ) . However, in post hoc analyses, those w h o lost at least 4.5 kg in each of the treatment conditions had a 2 5 % - 3 0 % reduction in diabetes risk, compared to those w h o lost no weight. This study suggests that substantial benefits m a y be achieved a m o n g those successful at losing weight, but that the overall benefit in clinical trials m a y be diluted by those w h o do not maintain weight loss. M o r e recently, results from the Finnish Diabetes Prevention Study provide yet more evidence that modest weight loss reduces the risk of Type 2 diabetes (Tuomilehto et al., 2001). The study randomized 522 middle-aged, overweight m e n and w o m e n with glucose tolerance to an intensive diet and exercise-based lifestyle intervention or a control group. Participants in the intervention group lost 4 . 7 % (4.2 kg) of their body weight after 1 year, compared to 0 . 9 % (0.8 kg) in the control condition. After an average follow-up of 3.2 years, the intervention group had a 5 8 % reduced risk of diabetes compared to the control group. The 4-year cumulative incidence of diabetes was 1 1 % for intervention participants, compared to 2 3 % for participants in the control group.
CVD and AAortality A n R C T of a lifestyle intervention (Singh et al., 1992) a m o n g 406 patients with coronary heart disease resulted in a 9 % weight loss (vs. 3 % in the control group), as w e U as significant improvements in lipid and blood pressure levels. The study also observed 4 0 % ^ 5 % reductions in cardiac events and all-cause mortality, and a 5 0 % reduction in deaths from stroke relative to controls. Post hoc analyses conducted a m o n g intervention participants indicated that the reduction in events w a s primarily driven by those w h o had lost weight during the year. These findings are consistent with the Lifestyle Heart Trial (Ornish et al., 1990, 1998), which showed that intensive hfestyle changes were associated with 8 % net
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weight loss and significant reductions in coronary stenosis over 5 years. It is important to note, however, that these lifestyle interventions were multifaceted and included a low-fat, high-fiber, and antioxidant-rich diet, along with counseling for smoking cessation, alcohol, stress, and exercise. Thus the extent to which health benefits were primarily due to weight loss or to dietary and behavioral changes is unclear. Interpretation of the RCTs is complicated by the fact that some of these trials were not weight loss studies per se, but instead were hfestyle interventions wherein weight loss was one of several effects. Because physical activity and dietary factors such as fat and sodium intake can influence health outcomes independently of body weight, it is difficult to separate the effects of these behaviors from the effects of weight loss. K n o w i n g the independent effects of weight loss, physical activity, and dietary change on health outcomes is important for understanding biological mechanisms. F r o m a public health perspective, however, identifying the feasible and appropriate interventions that improve long-term health status m a y be more important than isolating the mechanisms for their effects.
SUMMARY Several conclusions may be drawn from our review of the effects of weight loss on disease incidence and mortality: 1. Weight loss is related to many short-term benefits, primarily in terms of reduced risk factors for C V D and diabetes. These benefits have been consistently observed in studies of 3 to 12 months' duration, but rarely have been tested for more than 2 years. 2. Intentional weight loss does not increase mortality but m a y decrease mortality, especially a m o n g people with obesity-related health conditions. Although three observational studies and one N C T of lifestyle intervention suggest that weight loss enhances longevity a m o n g high-risk populations, more studies are needed to confirm this. Previous observations relating weight loss of u n k n o w n intent to increased mortality are probably explained by unintentional weight loss associated with preexisting disease. 3. Modest weight loss and lifestyle interventions can prevent hypertension and diabetes a m o n g those at high risk for these diseases. Benefits of modest weight loss (e.g., l % - 6 % ) on hypertension and diabetes have been demonstrated in R C T s . A combination of N C T s of surgical and lifestyle interventions have also suggested that diabetes m a y be prevented. 4. It is unclear whether intentional weight loss reduces C V D incidence. O n e R C T and one N C T have suggested that weight loss reduces C V D incidence and mortality, but observational studies have not found that intentional weight loss reduces C V D incidence. 5. There is a lack of studies on the effects of intentional weight loss on important health outcomes. R C T s would be an ideal approach to assess the effects of intentional weight loss on physical disability, osteoporotic fractures, and health-related quality of life. There is also a need for well-designed observational studies of this issue. Many fundamental questions about unintentional weight loss remain unanswered. Do the physiological benefits of short-term weight loss translate into long-term benefits on C V D incidence and mortality? Are there particular populations, such as elderly persons or those with preexisting diseases, a m o n g w h o m the health effects of intentional weight loss are enhanced or diminished? W h a t is the impact of different weight loss modalhies, such as dietary restriction and exercise, on quality-of-life? Could the quality-of-life benefits of in-
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tentional weight loss justify possible null effects on disease incidence and mortality? Finally, can weight loss interventions be implemented with reasonable effectiveness, safety, and cost through clinical and public health efforts? Clearly, R C T s of the long-term impact of intentional weight loss on disease incidence and mortality are needed, and several ongoing trials m a y provide some answers to these questions. T h e L o o k A H E A D (Action for Health in Diabetes) trial, a multicenter clinical trial funded by the National Institutes of Health, w a s recently inhiated to study the effects of weight loss on cardiovascular and other outcomes a m o n g overweight persons with Type 2 diabetes over a planned follow-up period of 11.5 years (Yanovski et al., 1999). T h e Diabetes Prevention Program, currently underway in the United States, is designed to estimate the impact of lifestyle interventions on the incidence of diabetes in overweight persons with I G T (Diabetes Prevention Program Research Group, 1999). Regardless of the results of ongoing R C T s , debates about the long-term health impact of intentional weight loss are likely to continue. Perhaps the scientific focus of obesity research will begin to m o v e toward the question of whether obesity prevention is ultimately more effective than obesity treatment in reducing disease incidence and mortality.
ACKNOWLEDGMENTS We thank Dr. Henry Kahn for his insightful comments on an earlier draft of this chapter.
REFERENCES Agurs-CoUins, T. D., Kumanyika, S. K., Ten Have, T. R., Si Adams-Campbell, L. L. (1997). A randomized controlled trial of weight reduction and exercise for diabetes management in older African-American subjects. Diabetes Care, 20, 1503-1511. Allison, D. B., ZannoUi, R., Faith, M . S., Heo, M., Pietrobelli, A., VanltaUie, T. B., Pi-Sunyer, F. X., & Heymsfield, S. B. (1999). Weight loss increases and fat loss decreases aU-cause mortality rate: Results from two independent cohort studies. International Journal of Obesity, 23, 603-611. Andersen, R. E., Wadden, T. A., Bartlett, S. J., Vogt, R. A., Si Weinstock, R. S. (1995). Relation of weight loss to changes in serum lipids and lipoproteins in obese women. American Journal of Clinical Nutrition, 62, 350-357. Andres, R., Muller, D. C , & Sorkin, J. D. (1993). Long-term effects of change in body weight on allcause mortality: A review. Annals of Internal Medicine, 119, 737-743. Blair, S. N., Shaten, J., BrowneU, K., Collins, G., Si Lissner, L. (1993). Body weight change, aU-cause mortality, and cause-specific mortality in the Multiple Risk Factor Intervention Trial. Annals of Internal Medicine, 119, 749-757. Centers for Disease Control and Prevention. (1997). Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U. S. Department of Health and H u m a n Services interim public health recommendation, November 1997. Morbidity and Mortality Weekly Report, 46, 1061-1065. Centers for Disease Control and Prevention. (1998). Hyperthermia and dehydration-related deaths associated with intentional rapid weight loss in three collegiate wrestlers—North Carolina, Wisconsin, and Michigan, November-December 1997. Morbidity and Mortality Weekly Report, 47, 105-108. Colditz, G. A., Willett, W . C , Rotnitzky, A., & Manson, J. E. (1995). Weight gain as ariskfactor for clinical diabetes mellitus in women. Annals of Internal Medicine, 122, 481-486. Dengel, J. L., Katzel, L. I., & Goldberg, A. P. (1995). Effect of an American Heart Association diet, with or without weight loss, on lipids in obese middle-aged and older men. American Journal of Clinical Nutrition, 62, 715-721. Diabetes Prevention Program Research Group. (1999). The Diabetes Prevention Program: Design and
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T., Ports, T. A., Kirkeeide, R. L., Hogeboom, C, Si Brand, R. J. (1998). Intensive lifestyk changes for reversal of coronary heart disease. Journal of the American Medical Association, 280, 2001-2007. Salamone, L. M., Cauley, J. A., Black, D. M., Simkin-SUverman, L., Lang, W., Gregg, E., Palermo, L., Epstein, R. S., Kuller, L. H., Sc Wing, R. (1999). Effect of a lifestyle intervention on bone mineral density in premenopausal women: A randomized trial. American Journal of Clinical Nutrition, 70, 97-103. Simkin-SUverman, L. R., Wing, R. R., Boraz, M . A., Meilahn, E. N., & Kuller, L. H. (1998). Maintenance of cardiovascular risk factor changes among middle-aged w o m e n in a lifestyle intervention trial. Women's Health: Research on Gender, Behavior, and Policy, 4, 255-271. Simkin-SUverman, L. R., Wing, R. R., Hansen, D. H., Klem, M . L., Pasagian-Macaulay, A. P., Meilahn, E. N., & KuUer, L. H. (1995). Prevention of cardiovascular risk factor elevations in healthy perimenopausal women. Preventive Medicine, 24, 509-517. Singh, R. B., Rastogi, S. S., Verma, R., Laxmi, B, Singh, R., Ghosh, S., Si Niaz, M . A. (1992). Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: Results of 1-year follow-up. British Medical Journal, 304, 1015-1019. Sjostrom, C. D., Lissner, L., Wedel, H., Si Sjostrom, L. (1999). Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: The SOS Intervention Study. Obesity Research, 7, 477-484. Sjostrom, C. D., Peltonen, M., Wedel, H., & Sjostrom, L. (2000). Differentiated long-term effects of intentional weight loss on diabetes and hypertension. Hypertension, 36, 20-25. Stefanick, M . L., Mackey, S., Sheehan, M., Ellsworth, N., HaskeU, W . L., & Wood, P. D. (1998). Effects of diet and exercise in men and postmenopausal w o m e n with low levels of H D L cholesterol and high levels of L D L cholesterol. N e w England Journal of Medicine, 339, 12-20. Strobel, R. J., Si Rosen, R. C. (1996). Obesity and weight loss in obstructive sleep apnea: A critical review. Sleep, 19, 104-115. Syngal, S, Coakley, E. H., Willett, W . C , Byers, T., WiUiamson, D. F., & Colditz, G. A. (1999). Longterm weight patterns and risk for cholecystectomy in women. Annals of Internal Medicine, 130, 471-477. Thompson, M . P., & Morris, L. K. (1991). Unexplained weighr loss in the ambulatory elderly. Journal of the American Geriatrics Society, 39, 497-500. Torieson, P. A., Birkeland, K. I., Anderssen, S. A., Hjermann, I., Holme, I., Sc Urdal, P. (1997). Lifestyle changes may reverse development of the insulin resistance syndrome. Diabetes Care, 20, 26-31. Trials of Hypertension Prevention (TOHP) Collaborative Research Group. (1992). Effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Journal of the American Medical Association, 267, 1213-1220. Trials of Hypertension Prevention (TOHP) Collaborative Research Group. (1997). Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. Archives of Internal Medicine, 157, 657-667. Tuomilehto, J., Lindstrom, J., Eriksson, J. G., Valle, T. T., Hamalainen, H., Uanne-Parikka, P., Keinanen-Kiukaanniemi, S., Laakso, M., Louheranta, A., Rastas, M., Sc Salminen, V. (2001). Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N e w England Journal of Medicine, 344, 1343-1350. Wadden, T. A. (1993). Treatment of obesity by moderate and severe caloric restriction: Results of clinical research trials. Annals of Internal Medicine, 119(7, Pt. 2), 688-693. Wadden, T. A., VanltaUie, T. B., & Blackburn, G. A. (1990). Responsible and irresponsible use of very-low-calorie diets in the treatment of obesity. Journal of the American Medical Association, 263, 83-85. Weinsier, R. L., Wilson, L. J., Sc Lee, J. (1995). Medically safe rate of weight loss for the treatment of obeshy: A guideline based on risk of gallstone formation. American Journal of Medicine, 98, 115-117. Whelton, P. K., Appel, L. J., Espeland, M., Applegate, W . B., Ettinger, W . H., Kostis, J. B., Kumanyika, S., Lacy, C. R., Johnson, K. C , Folmar, S., & Cutler, J. A. (1998). Sodium reduction and
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weight loss in the treatment of hypertension in older persons. Journal of the American Medical Association, 279, 839-846. Williamson, D. F. (1996). "Weight cycling" and mortality: H o w do the epidemiologists explain the role of intentional weight loss? Journal of the American College of Nutrition, 15, 6-13. Williamson, D. F. (1997). Intentional weight loss: Patterns in the general population and its association with morbidity and mortality. International Journal of Obesity, 21 (Suppl. 1), S14-S19. Williamson, D. F., & Pamuk, E. R. (1993). The association between weight loss and increased longevity: A review of the evidence. Annals of Internal Medicine, 119(7, Pt. 2), 731-736. Williamson, D. F., Pamuk, E., Thun, M., Flanders, D., Byers, T., Sc Heath, C. (1995). Prospective study of intentional weight loss and mortality in never-smoking overweight U. S. white w o m e n aged 40-64 years. American Journal of Epidemiology, 141, 1128-1141. Williamson, D. F., Pamuk, E., Thun, M., Flanders, D., Byers, T., Sc Heath, C. (1999). Prospective study of intentional weight loss and mortality in overweight white m e n aged 40-64 years. American Journal of Epidemiology, 149, 491-503. Williamson, D. F., Thompson, T. J., Thun, M., Flanders, D., Pamuk, E., & Byers, T. (2000). Intentional weight loss and mortality among overweight persons with diabetes. Diabetes Care, 23, 1499-1504. Wing, R. R. (1992). Weight cycling in humans: A review of the literature. Annals of Behavioral Medicine, 14, 113-119. Wing, R. R., Epstein, L. H., Paternostro-Bayles, M., Kriska, A., Nowalk, M . P., & Gooding, W . (1988). Exercise in a behavioral weight control programme for obese patients with Type 2 (noninsulin-dependent) diabetes. Diabetologia, 31, 901-909. Wing, R. R., Koeske, R., Epstein, L. H., Nowalk, M . P., Gooding, W., Si Becker, D. (1987). Longterm effects of modest weight loss in Type II diabetic patients. Archives of Internal Medicine, 147, 1749-1753. Wing, R. R., Venditti, E., Jakicic, J. M., PoUey, B. A., Si Lang, W . (1998). Lifestyle intervention in overweight individuals with a family history of diabetes. Diabetes Care, 21, 350-359. Wolf, A. M., & Colditz, G. A. (1996). Social and economic effects of body weight in the United States. American Journal of Clinical Nutrition, 11, 660-672. Wood, P. D., Stefanick, M . L., W U U a m s , P. T., Si HaskeU, W . L. (1991). The effects on plasma lipoproteins of a prudent weighr-reducing diet, with or without exercise, in overweight m e n and women. N e w England Journal of Medicine, 325, 461-466. Yaari, S., Si Goldbourt, U. (1998). Voluntary and involuntary weight loss: Associations with longterm mortality in 9228 middle-aged and elderly men. American Journal of Epidemiology, 148, 546-555. Yanovski, S. Z., Bain, R. P., & WiUiamson, D. F. (1999). Report of a National Institutes of Health-Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons. American Journal of Clinical Nutrition, 69, 366-372.
8
Psychosocial of O b e s i t y
C o n s e q u e n c e s
a n d
W e i g h t
Loss
T H O M A S A. W A D D E N LESLIE G . W O M B L E ALBERTJ. S T U N K A R D D R E W A. A N D E R S O N
Stereotypes about obesity abound. This is particularly true concerning psychological characteristics attributed to obese persons and to the effects of weight loss. In m a n y cases, popular views are contradictory. Overweight individuals are frequently portrayed as jolly, but equally often as depressed or anxious. Advertisements picture dieters as brimming with selfconfidence, energy, and sex appeal, while some researchers contend instead that they are vulnerable to binge eating, irritability, and emotional distress. This chapter reviews empirical studies of the psychosocial consequences of obesity and weight loss. Studies are described under four general categories: (1) the prejudice and discrimination to which obese individuals are subjected; (2) the effects of this hostile environment on their psychological functioning; (3) the behavioral and psychosocial effects of dieting and weight loss; and (4) the consequences of the aU-too-frequent occurrence of weight loss and regain (i.e., weight cycling).
PREJUDICE A N D D I S C R I M I N A T I O N A G A I N S T O B E S E I N D I V I D U A L S Prejudice History shows that prejudice against obese individuals is not simply a product of society's current worship of a thin ideal. A s early as the 12th century, Buddhists stigmatized obesity as the karmic consequence of moral failing (Stunkard, LaFleur, & W a d d e n , 1998). In the Christian culture, gluttony w a s considered one of the seven deadly sins, and A d a m was labeled a glutton for eating the apple (Stunkard et al., 1998). Today obesity is k n o w n to have a significant genetic component; yet disparagement of overweight and obese individuals
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persists as what Sobal and Stunkard (1989) have called "the last socially acceptable form of prejudice" (p. 417). Such prejudice has been observed in children as young as 6 years of age, w h o labeled silhoueti:es of an overweight child as "lazy, dirty, stupid, ugly, cheats, and lies" (Staffieri, 1967). W h e n shown black-and-whitefinedrawings of an obese child and children with various handicaps, including missing hands and facial disfigurement, both children and adults rated the obese child as the one with w h o m they least wished to play (Goodman, Dornbusch, Richardson, & Hastorf, 1963; Richardson, G o o d m a n , Hastorf, & Dornbusch, 1961). In a similar study, college students rated embezzlers, cocaine users, shoplifters, and blind people as more suitable marriage partners than obese individuals (Venes, Krupka, & Gerard, 1982). Almost aU obese and overweight adolescent girls in one sample reported having been verbally abused (Neumark-Sztainer, Story, & Faibisch, 1998). Prejudice against the obese extends to heahh care professionals. Numerous studies have reported that physicians have negative attitudes toward obesity (Harris, H a m a d a y , & M o c h a n , 1999; Maddox, Back, &c Liederman, 1968; M a d d o x & Liederman, 1969; Olson, Schumaker, & Yawn, 1994; R a n d & Macgregor, 1990).
Discrimination Prejudice against obese individuals is associated with discrimination that affects virtually every domain of life. A n exemplary study by Gortmaker, Must, Perrin, Sobol, and Dietz (1993) foUowed 10,039 overweight and normal-weight adolescents for 7 years. At the end of this time, overweight females had completed significantly fewer months of school, were less likely to be married, and had lower household incomes than nonoverweight females, despite comparable intellectual aptitudes. Overweight males were less likely to be married than were their nonoverweight peers. By contrast, people with other chronic conditions such as asthma, rheumatoid arthritis, and cerebral palsy did not differ from the nonoverweight participants on any of these outcomes. Other studies similarly found that obese individuals had lower acceptance rates into prestigious colleges than nonobese students did, despite comparable scholastic performance in the two groups (Canning & Mayer, 1966; Pargaman, 1969). Studies from the 1960s and 1970s found evidence of weight-related discrimination in the workplace. Sixteen percent of employers interviewed by Roe and Eichwort (1976) reported that they would not hire obese individuals under any conditions, and an additional 4 4 % would hire them only under special circumstances. A study in 1974, w h e n salaries were lower, revealed that only 9 % of executives w h o earned $25,000-$50,000 were more than 10 pounds overweight, whereas 3 9 % of those earning $10,000-$20,000 were simUarly overweight ("Fat Execs Get Slimmer Paychecks," 1974). The authors of this study calculated that each pound of fat cost an executive $1,000 per year. M o r e recent laboratory studies, which have experimentally manipulated job applicants' perceived weights, have found a strong bias against obese individuals in almost every stage of employment—selection, placement, compensation, promotion, discipline, and discharge (Frieze, Olson, & Good, 1990; Roehling, 1999). This bias seems to be more pronounced for w o m e n than for men. A study, for example, by Pingitore, Dugoni, Tindale, and Spring (1994) asked participants to rate videotaped job interviews of actors w h o appeared to be of normal weight or were m a d e up to look overweight. The applicant's apparent weight was the strongest determinant of the hiring decision, accounting for 3 5 % of the variance. The same applicant, w h e n m a d e to look overweight, was selected significantly less often than w h e n he or she appeared to be of average weight. This bias was stronger against overweight-appearing w o m e n than against such men.
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Field studies, which usually involve national samples of self-reported survey data, have yielded simUar but less consistent results (Roehling, 1999). A longitudinal survey by Averett and K o r e n m a n (1996) found that the wages of obese European American w o m e n were lower than those of their average-weight peers. This effect w a s not found in African American females. By contrast, a m o n g overweight and underweight m e n , there w a s weaker and less consistent evidence of a wage penalty. Despite evidence of discrimination against obese persons in the workplace, regrettably, such practice does not appear to violate current federal law (Roehling, 1999). Title VII, which safeguards employees from discrimination, does not designate obesity as a protected characteristic. Under Title VII, disparate treatment occurs w h e n an employer treats people differently because of race, color, religion, sex, or national origin. In a few cases, obese individuals have prevailed w h e n their weight w a s associated with a protected characteristic. In 1982, a court determined that Continental Airlines applied its weight restriction policy only to female employees, and therefore the policy resulted in discrimination based on gender (Gerdom v. Continental Airlines, 1982). Obesity has, in a few instances, been protected as a disability under federal law. T o attain this status, a person must be either extremely obese ( 1 0 0 % above ideal weight) or obese because of a physiological condition (Roehling, 1999). Because less than 3 % of the obese population is extremely obese, this leaves the great majority of obese individuals vulnerable to discrimination. Similarly, although obesity is k n o w n to be under significant genetic control, only rare circumstances (such as absolute leptin deficiency or Cushing's disease) would allow a practitioner to attribute a patient's obesity 1 0 0 % to a physiological condition. Studies clearly demonstrate that obese people bear overt discrimination and prejudice in today's society. However, despite the preponderance of evidence, this discrimination is rarely considered illegal according to federal law. S o m e states and municipalities have passed laws barring discrimination based on weight (Roehhng, 1999). W e beUeve that it is time for the federal government to do the same.
P S Y C H O S O C I A L S T A T U S O F O B E S E INDIVIDUALS Given the ubiquitous prejudice and discrimination that obese persons endure, it would not be surprising to discover that they experience greater psychological distress than their nonobese peers. This appears to be the case with individuals w h o seek weight reduction; distress is probably one of the factors that leads them to seek weight loss. This section reviews the psychosocial status of obese individuals encountered in chnical settings, as well as that of unselected obese individuals from the general population.
Psychosocial Status of Obese Individuals in the General Population Psychological Functioning Several early studies found few differences in psychological functioning between obese and nonobese individuals in the general population (Friedman & Brownell, 1995; Stunkard & W a d d e n , 1992; W a d d e n & Stunkard, 1985). For example, M o o r e , Stunkard, and Stole (1962) examined 1,660 people in midtown Manhattan and found that obese individuals scored significantly higher than nonobese persons on only three of nine measures of psychological functioning—immaturity, suspiciousness, and rigidity. Differences between groups
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on these measures were so small, however, as to be judged chnically insignificant. Stewart and Brook (1983) simUarly observed only small differences between obese and nonobese subjects. In a study of 5,817 persons, obese individuals were significantly less depressed and anxious than were theh nonobese counterparts. Results of two British studies (Crisp & McGuiness, 1976; Silverstone, 1968) and three European investigations (Hallstrom & N o p pa, 1981; Kittel, Rustin, Dramaix, DeBacker, & Kornitzer, 1978; Larsson, 1978) also found few differences in psychological status between obese and nonobese persons in the general population. The finding of essentially normal psychological functioning in obese individuals is heartening. As reviewed by Friedman and Brownell (1995), however, some of these early investigations had shortcomings that included (1) the study of small convenience samples rather than nationally representative surveys; (2) the use of variable criteria to define overweight and obesity; (3) the often hmited assessment of psychological status by paper-andpencU inventories that did not yield chnical diagnoses; and (4) the failure to include appropriate control groups. SimUarly, W a d d e n and Stunkard (1985) noted that w o m e n appeared to be at higher risk than m e n of emotional complications because of the greater social pressures on females to be thin. M a n y early studies, however, did not adequately examine gender differences, particularly at the highest weight levels. At least two studies have addressed these limitations. In a nationally representative sample of 32,000 persons 25-74 years of age, Istvan, Zavela, and Weidner (1992) found a positive (though weak) relation in w o m e n between body mass index (BMI) and symptoms of depression, as measured by the Center for Epidemiologic Studies Depression (CES-D) scale (Radloff, 1977). A s shown in Figure 8.1, w o m e n in the highest B M I quintUe w h o had ever smoked (in the past or present) had significantly higher CES-D total scores than did w o m e n of similar smoking status w h o fell in the lower B M I quintiles. N o relationship, however, was found between B M I and C E S - D scores in w o m e n w h o had never smoked. Istvan and colleagues (1992) hypothesized that depression in obese w o m e n w h o had ever smoked might have resulted from the failure of smoking to reduce weight, as these w o m e n might have expected it to. In contrast to w o m e n , no relationship was observed in m e n between body weight and C E S - D scores, regardless of smoking status. Carpenter, Hasin, Allison, and Faith (2000) used a structured interview to estabhsh a diagnosis of major depression in a nationally representative sample of 40,289 persons. They used criteria comparable to those proposed in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). They found that obese w o m e n , as defined by having a B M I > 30 kg/m-^, were 3 7 % more likely to have experienced major depression in the past year than were average-weight w o m e n (defined as having a B M I between 20.8 and 29.9 kg/m^). Obese w o m e n also were significantly more likely to report suicidal ideation and suicide attempts (see Table 8.1 for odds ratios). By contrast, in m e n , obesity was associated with significantly reduced risks of major depression and suicide attempts. Being underweight (defined as having a B M I < 20.8 kg/m^), not obese, was associated with an increased risk of all three adverse events in men. These last two studies clearly suggest that excess weight has different psychosocial consequences in males and females (in the general population), as reviewed by other investigators (Polivy & H e r m a n , 1985; Striegel-Moore, 1993). W o m e n and teenage girls appear to be particularly vulnerable to symptoms of low self-esteem and depression w h e n they fail, in their o w n eyes, to measure up to the thin ideal that haunts them on video screens and magazine covers. Their perception that they are overweight, rather than their actual body weight, m a y well be the more important factor in precipitating emotional complications (Wadden, Foster, Stunkard, & Linowitz, 1989). W o m e n of upper-middle to upper socioeconomic status (SES) would appear to be particularly vulnerable to weight-related distress.
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148 13
10 4
o o
7.8
o UJ o
5.2
2.6 -
1
2
3
4
5
Body Mass Quintile
FIGURE 8.1. Mean reported depressive symptoms, as measured by the Center for Epidemio Studies Depression (CES-D) scale (Radloff, 1977), among women as a function of smoking status and body mass index quintile following regression adjustment for age and years of education. Squares, women who currently smoked; circles, women who had smoked in the past; triangles, women who had never smoked. From Istvan, Zavela, and Weidner (1992). Copyright 1992 by Nature Publishing Group. Reprinted by permission.
given the greater social sanctions against obesity at these SES levels (Sobal &C Stunkard, 1989). Some have suggested that minority women may be protected against such adverse effects because they do not appear to seekfiguresas thin as those desired by European American women (Fitzgibbon, Blackman, & AveUone, 2000). Results, however, of the Carpenter and colleagues (2000) study showed the same relationship between obesity and depression in African American women as in European American women, after SES was controlled for. Although health care providers should be alert to the possibility of depressive symptoms in obese women (particularly those w h o smoke), neither they nor the general public should mistakenly conclude that most obese females have significant psychological problems; they do not. Although the risk of depression in the obese w o m e n studied by Carpenter and colleagues (2000) was 3 7 % greater than that in average-weight women, the authors did not present data on the absolute risk of depression in either group. If, for example, 1 0 % of average-weight women reported depression in the prior year, as shown from other surveys (Kessler et al., 1994), then we could estimate that 13.7% of obese w o m e n experienced depression during the same time. This increase is certainly of concern, but should not be used to inadvertently support stereotypes that a majority of obese w o m e n (or men) suffer from depression, anxiety, or otber complications that are supposedly responsible for their obesity. Such beliefs are simUar to previous erroneous assertions that obese individuals have a specific personahty style. Personality is as diverse in obese individuals as h is in those of average weight (Wadden & Stunkard, 1985).
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TABLE 8.1. Adjusted Odds Ratios for the Categorized and Continuous Weight-by-Sex Interactions Major depression. Suicide ideation. Suicide attempts, O R ( 9 5 % CI) Continuous weight (BMI)" Men Women Categorical weight contrasts Underweight vs. average-weight Men Women Obese vs. average-weight Men Women
O R ( 9 5 % CI)
O R ( 9 5 % CI)
0.55(0.48,0.63) 1.22 (1.06, 1.40)
0.74(0.64,0.86) 1.22 (1.13, 1.32)
0.45(0.40,0.51) 1.22 (0.91, 1.63)
1.25(1.18,1.32) 1.02 (0.84, 1.23)
1.81(1.71,1.89) 1.10 (0.88, 1.34)
1.77(1.34,2.33) 0.88 (0.55, 1.41)
0.63(0.60,0.67) 1.37 (1.09, 1.73)
1.02(0.98,1.06) 1.20 (0.96, 1.50)
0.63(0.48,0.83) 1.23 (0.74,2.03)
Note. OR, odds ratio; 9 5 % CI, 9 5 % confidence interval. All ORs are adjusted for race, age, education, past-year income, self-reported disease history, and the race-by-weight interaction term. From Carpenter, Hasin, Allison, and Faith (2000). Copyright 2000 by the American Public Health Association. Reprinted by permission. "Odds ratios are presented for a 10-unit change in body mass index (BMI).
Quality of Life Rather than causing clinically significant depression or anxiety, obesity's most significant adverse psychosocial effect m a y be in decreasing "health-related quality of life." This latter term refers to the burden of suffering and limitations in work and social functioning associated with illness. Health-related quality of life is most commonly measured by the 36-Item Short-Form Health Survey (SF-36), which evolved from the Medical Outcomes Study, developed by W a r e and Sherbourne (1992). The 36 questions of the SF-36 measure eight domains of functioning: Physical Functioning, Role Limitations due to Physical Health Problems, Social Functioning, Bodily Pain, General Mental Heahh, Role Limitations due to Emotional Problems, Vitality, and General Health Perceptions. Numerous surveys of obese individuals in the general population, as well as the clinic, have revealed complaints of pain, reduced vitality, and impairment in social or occupational roles. LePen, Levy, Loos, Bunzet, and Basdevant (1998), for example, found that persons with a B M I > 30 kg/m^ scored significantly worse on the Physical Functioning, Bodily Pain, General Health Perceptions, and Vitality scales of the SF-36 than did nonobese individuals. Barofsky, Fontaine, and Cheskin (1998) found that almost 5 0 % of 312 obese patients w h o sought weight reduction reported moderate to severe pain, particularly in the lower back. Their reports of pain were greater than those of patients with congestive heart failure and human immunodeficiency virus. In a nationally representative sample of 12,905 Dutch m e n and w o m e n . Lean, H a n , and Seidell (1999) found that a large number of participants with a B M I > 30 kg/m2 experienced shortness of breath w h e n walking uphill (i.e., 4 6 % w o m e n and 3 4 % m e n ) , as well as chronic low back pain (i.e., 2 5 % w o m e n and 2 0 % men). These symptoms were reported significantly lessfrequentlyby nonobese persons (i.e., B M I < 30 kg/m^). Doll, Petersen, and Stewart-Brown (2000) found that increasing B M I was associated with increased physical comorbidities and with reports of poorer physical health. Others have shown that obese persons experience self-consciousness or embarrassment w h e n eating in restaurants, swimming in public, or shopping for food or clothing (Karlsson, Sjostrom, & Sullivan, 1998). r , , . , Taken together, these findings suggest that a large proportion of obese individuals in the general population experience undesired physical or social consequences of their weight that diminish their quality of life. These emotional consequences typically do not
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require professional attention, but nonetheless are likely to detract from the individuals' enjoyment of work and leisure activities. Further studies are needed to identify those individuals w h o are at greatest risk of progressing from decreased quality of life to clinically significant anxiety or depression. A s discussed later, our clinical impression is that these individuals are likely to be heavier (i.e., B M I > 4 0 kg/m^) and to have more serious health complications.
Psychological Status of Obese Individuals in Clinical Populations In contrast to population studies, investigations of obese individuals in clinical settings have consistently reported significant psychopathology (Friedman & Brownell, 1995; Stunkard & W a d d e n , 1992; W a d d e n & Stunkard, 1985). Reports in the 1950s by psychodynamically oriented psychiatrists described patients' unconscious conflicts and difficulties in establishing intimate relationships, which purportedly resulted in pathological eating and obesity. The 1960s and 1970s witnessed the publication of at least 10 studies that described elevations in obese individuals on the Depression, Hypochondriasis, and Impulsivity scales of the Minnesota Multiphasic Personality Inventory ( M M P I ; Hathaway & McKinley, 1967) (for a review, see W a d d e n & Stunkard, 1985). In their review of the literature, Friedman and Brownell (1995) found a moderate effect size (mean d = 0.52) for differences in rates of depression between population controls and obese individuals presenting for treatment. W a d d e n and Stunkard (1985) and Friedman and Brownell (1995) noted that these early clinical studies had numerous shortcomings, a m o n g which was the failure, reported before, to include appropriate control groups. Increased anxiety and depression, for example, are routinely observed in patients w h o seek medical care, regardless of their body weight. Swenson, Pearson, and Osborne (1973) administered the M M P I to 18,328 w o m e n w h o underwent general medical or surgical procedures. M e a n scores on the Hypochondriasis and Depression scales were 61 and 60, respectively, equal to one standard deviation above the mean. This was the criterion used to define psychopathology in the studies of obese individuals described above. This finding does not diminish the distress experienced by obese individuals w h o seek weight reduction. It does, however, place it in context; untoward emotional responses to medical conditions are not unique to obese individuals. O n e of the most thorough studies of psychopathology was conducted by Fitzgibbon, StoUey, and Kirschenbaum (1993), w h o examined the psychological status of obese persons w h o did (n = 57) or did not (n = 57) seek weight reduction, as w e U as that of nonobese individuals (n - 57) w h o were not seeking medical care. The obese treatmentseeking patients reported significantly greater symptoms of distress, as measured by the Borderline S y m p t o m Inventory (Conte, Plutchik, Karaus, & Jerrett, 1980), than did either the obese or nonobese individuals w h o did not seek treatment. These latter two groups did not differ significantly from each other. Obese persons seeking treatment also reported significantly greater psychopathology than nonobese individuals, as assessed by the S y m p t o m Checklist 90 (Derogatis, Lipman, & Covi, 1973), with no other differences between groups. This study clearly indicates that obese individuals w h o seek treatment are hkely to have higher rates of psychopathology than are obese individuals in the general population. Significant emotional distress (i.e., symptoms of depression or anxiety) is hkely to be one of the factors that prompts people to seek professional assistance. In addition to m o o d disorders, these individuals appear more likely than obese individuals in the general population to suffer from binge-eating disorder (BED) and body image dissatisfaction.
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Binge-Eating Disorder As reviewed by Stunkard in Chapter 6 of this volume, binge eating is characterized by the consumption of an objectively large a m o u n t of food in a brief period (i.e., less than 2 hours), during which the individual experiences a subjective loss of control. W i t h B E D , overeating is not followed by purging or other compensatory behavior, which distinguishes this condition from bulimia nervosa. B E D w a s originally estimated, by self-report, to occur in approximately 3 0 % of obese individuals w h o sought treatment (Spitzer et al., 1992, 1993). W h e n diagnosed by expert examiners, however, the prevalence appears to be as low as 1 0 % - 1 5 % (Stunkard, Chapter 6, this volume). This reduced rate is stUl several times greater than that observed in the general population, again suggesting that the presence of B E D motivates patients to seek treatment (Spitzer et al., 1992). Binge eating appears to account for increased rates of depression within the population of obese individuals w h o seek weight reduction. Several early studies found that patients with severe binge eating, as diagnosed by the Binge Eating Scale (BES; Gormally, Black, Daston, & Rardin, 1982), reported significantly greater s y m p t o m s of depression, as m e a sured by the Beck Depression Inventory (BDI; Beck & Steer, 1987), than did obese individuals with moderate or n o binge eating. A s s h o w n in Table 8.2, the m e a n B D I scores of patients with severe binge eating, as determined in three studies, ranged from 14.1 to 17.5. These scores are indicative of mild depression and reflect the need for further clinical evaluation. By contrast, the scores of obese individuals without severe binge eating fell in the normal range. T w o of three later studies also found greater depression in patients w h o were diagnosed with B E D , as defined by Spitzer and coUeagues (1992). Obese patients with B E D studied by Kuehnel and W a d d e n (1994) and by Mussell, Peterson, and colleagues (1996) scored in the mildly depressed range and at least 5 points higher than obese individuals without B E D , w h o in both studies scored in the normal range. By contrast, patients diagnosed with B E D by Brody, Walsh, and Devlin (1994) did not score in the depressed range or even significantly higher than obese patients without B E D . T h e overwhelming majority of research in this area indicates that, compared to obese persons without B E D , obese individuals with B E D are m o r e likely to report not only increased s y m p t o m s of depression but also lower self-esteem, greater s y m p t o m s of borderline personality disorder, and a significantly greater lifetime prevalence of any Axis I disorder.
T A B L E 8.2. M e a n BDI Scores of Binge-Eating and Non-Binge-•Eating Patients as Assessed by Self-Report or Interview
BDI score Study
Method of assessment
Marcus, Wing, & Hopkins (1988) Telch & Agras (1994) Wadden, Foster, Letizia, & Wilk (1993) Brody, Walsh, & Devlin (1994) Kuehnel 8c Wadden (1994) Mussell, Peterson, etal (1996)
BES BES BES Q E W P with interview Q E W P with interview SCID—Patient Version
n
Binge-eating Non-binge-eating
56 107 86
17.5 ± 5.4 14.1 ±7.3 17.0 ± 8.4
7.7 ±5.2 10.2 ± 6.0 7.0 ± 4.7
69 70 128
8.7 ± 6.5 15.5 ± 6.9 11.4 ±7.3
7.8 ± 5.1 8.1 ± 5.3 6.1 ±4.5
Note. QEWP, Questionnaire on Eating and Weight Patterns (Spitzer et al., 1992); SCID, Structured Clinical Interview for DSM-m-R (Spitzer, Williams, Gibbon, & First, 1990); BES, Binge Eating Scale (Gormally, Black, Daston, & Rardin, 1982); BDI, Beck Depression Inventory (BDI; Beck & Steer, 1987).
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including substance abuse or dependence (Eldredge & Agras, 1996; Mussell, Mitchell, et al., 1996; MusseU, Peterson, et al., 1996; Specker, de Z w a a n , R a y m o n d , & MitcheU, 1994; Tanovsky, Wilfley, Spurrell, Welch, & Brownell, 1997; Telch & Agras, 1994, Williamson & Martin, 1999; Yanovski, Nelson, Dubbert, & Spitzer, 1993). Findings concerning B E D reveal the importance of distinguishing between obese individuals w h o do and do not have an eating disorder, in addition to their weight problem. A majority of obese individuals do not have an eating disorder, and these persons have essentially normal psychological functioning, whether encountered in the general population or the chnic (BrowneU & W a d d e n , 1991; Friedman & BrowneU, 1995). Obese individuals w h o suffer from binge eating are more likely to report psychological complications. Once again, this is true whether these individuals are encountered in treatment settings or in the general population (French, Jeffery, Sherwood, & Neumark-Sztainer, 1999; Telch & Stice, 1998). The relations among obesity, binge eating, and depression are not well understood, as discussed by Stunkard in Chapter 6 of this volume. It is not clear whether depressed m o o d is secondary to bjnge eating or whether binge eating is an expression of depression of other psychopathology. Similarly, the relation between dieting and binge eating is uncertain, as also noted by Stunkard in Chapter 6. From a clinical standpoint, however, binge eating is a reliable marker for symptoms of depression and indicates the need for further evaluation of mood.
Body Image Dissatisfaction Body image dissatisfaction is far more c o m m o n in obese individuals than is binge eating (CargiU, Clark, Pera, Niaura, & Abrams, 1999; Cash, Counts, & Huffine, 1990; Foster, W a d d e n , & Vogt, 1997). In fact, such dissatisfaction is so pervasive in adolescent girls, even those of average weight, as to be described as a "normative discontent" (Rodin, 1993). The nature, etiology, and prevalence of body image dissatisfaction are reviewed by Sarwer and Thompson in Chapter 21 of this volume. Obese w o m e n studied by Sarwer, W a d d e n , and Foster (1998) reported significantly greater body image dissatisfaction than average-weight controls, as assessed by the Body Dysmorphic Disorder Examination—Self-Report (Rosen &c Reiter, 1996). Obese participants, however, did not score significantly higher on depression, with m e a n B D I values of 7.7 and 7.0, respectively. Thisfindingraises questions concerning whether body image dissatisfaction is associated with clinically significant distress, in the same manner as binge eating. Sarwer and colleagues (1998) found that approximately one-third to one-half of their obese w o m e n reported that their upset about their shape or appearance affected their social interactions. Such upset could be associated witb a subchnical syndrome characterized by frequent negative self-statements, avoidance of social interactions, and camouflaging of body parts. A small minority of obese individuals w h o seek treatment, however, are likely to suffer from body image dissatisfaction that is clearly associated with clinically significant depression or related complications. Stunkard and Mendelson (1961, p. 328) described a group of patients with body image disparagement w h o believed that their bodies were "ugly and despicable" and that others "viewed them with hostihty and contempt." Their body image disturbance took the form of an overwhelming preoccupation with their obesity, "often to the exclusion of any other personal characteristics." Sarwer and colleagues (1998) appear to have observed a similar phenomenon in 8%> of their sample w h o met the criteria for body dysmorphic disorder. This disorder is defined in D S M - I V as a preoccupation with an imagined or slight defect in appearance that causes clinically significant distress or impairment in social, occupational, or other important areas of functioning (American Psychiatric Association, 1994). Patients with body dysmorphic disorder scored an average of 13.2 on the BDI,
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as compared with a score of 7.2 for patients w h o reported body image dissatisfacrion but did not meet criteria for the disorder. Further research is needed to determine the prevalence of severe body image dissatisfaction (as described in these last t w o investigations) in both clinical and community samples. Further investigation is also needed of the etiology of this condition. Contributory factors appear to include a childhood history of weight-related teasing by peers (Grilo, Wilfley, BrowneU, & Rodin, 1994), as well as parental derision (Stunkard & Mendelson, 1961). In addition, t w o studies found that body image dissatisfaction w a s m o r e pronounced in obese individuals with binge eating than in those without binge eating, even after level of depression w a s controUed for (French et al. 1999; MusseU, Peterson, et al., 1996). Psychological Status of Extremely Obese Individuals Numerous studies have revealed a strong linear relation between BMI and the risk of health complications such as T y p e 2 diabetes and cardiovascular disease; the greater the B M I , the greater the likelihood of adverse heahh consequences. In the Nurses' Health Study, for example, w o m e n with a B M I > 4 0 kg/m^ had at least a twofold greater risk of fatal and nonfatal myocardial infarction than did those with a B M I of 27-29 kg/m^ and at least a fourfold greater risk than individuals with a B M I of 19-22 kg/m^ (Manson et al., 1995). W e suspect that individuals with extreme obesity (i.e., B M I > 4 0 kg/m^) are similarly at the greatest risk of adverse psychological complications of obesity. This is because of the greater prejudice and discrimination to which they are probably subjected, as well as the greater medical complications associated with their obesity. Sullivan and colleagues (1993) reported significantly poorer general mental well-being in extremely than in moderately obese persons. These authors, however, did not report whether there were differences between these t w o groups in depression or anxiety. In a pilot investigation, w e compared depression and self-esteem scores of patients with a B M I < 4 0 kg/m^ versus > 4 0 kg/m^, all of w h o m sought weight reduction at the University of Pennsylvania's clinic. Patients in thefirstgroup were treated by pharmacotherapy, while those in the second were candidates for bariatric surgery. A s s h o w n in Table 8.3, patients with a B M I > 4 0 kg/m^ reported significantly greater symptoms of depression, as well as lower self-esteem, than did patients with a B M I < 4 0 kg/m^. Those in the former group scored in the mild range of depression. Further studies of this issue, with larger samples, are clearly needed. T h e results of the pilot study described above, as well as clinical experience, lead us to encourage practitioners
T A B L E 8.3. Depression and Self-Esteem Scores of Patients Treated by Bariatric Surgery or Pharmacotherapy
Variable Age (yr) Weight (kg) BMI (kg/m2) Education (yr) Depression Self-esteem
Pharmacotherapy patients B M I < 40 kg/m^ (n = 40)
Bariatric surgery patients B M I > 40 kg/m2 (« = 137)
P
42.3 ± 9.0 98.7 ±9.0 36.0 ±2.2 15.7 ±1.9 9.2 ±7.8 16.0 ±5.0
40.1 ±9.6 144.1 ±29.1 52.7 ± 9.5 13.6 ±2.0 16.9 ±11.0 22.9 ± 2.5
<.05 <.001 <.001 <.001 <.001 <.01
Note. BMI, body mass index. Depression was assessed by the Beck Depression Inventory (Beck & Steer, 1987) and selfesteem by the Rosenberg Self-Esteem Inventory (Rosenberg, 1965). Higher scores on both inventories indicate greater complications. Sample size for group with BMI a 40 kg/m^ was 137 with the exception of self-esteem, which was 44.
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to pay particular attention to the psychological status of extremely obese individuals. As B M I increases beyond 40 kg/m^, these individuals are increasingly likely to experience health complications that limit their functioning at work and at h o m e , and thus precipitate depression or other untoward psychological reactions. Binge eating also appears to be comm o n in these individuals (Hsu, Betancourt, & SuUivan, 1996), and two studies have reported higher-than-expected rates of sexual abuse in persons with extreme obesity (Brewerton, O'NeU, Dansky, & Kilpatrick, 1999; Felitti, 1991). W a d d e n , Sarwer, Arnold, Gruen, and O'NeU (2000) have described elsewhere the psychological status and assessment of obese individuals w h o seek bariatric surgery.
P S Y C H O S O C I A L EFFECTS O F D I E T I N G A N D W E I G H T L O S S Dieting, the principal treatment for obesity, has been the subject of significant controversy during the past decade, as discussed by Foster and M c G u c k i n in Chapter 2 4 of this volume. Several critics have charged that "diets don't work," because most people regain their lost weight within 5 years (Garner &c Wooley, 1991; Goodrick & Foreyt, 1991). It has also been charged that dieting is associated with adverse emotional responses (e.g., depression) and m a y precipitate binge eating (Polivy & H e r m a n , 1985). These charges appear to be without merit. In a recent review, the National Task Force on the Prevention and Treatment of Obesity (2000) concluded that dieting in overweight and obese individuals is not associated with adverse psychosocial or behavioral effects. The second half of this chapter briefly examines the data on which these conclusions were based, and also assesses the effects of weight loss on quality of life and body image. The review is limited to weight loss efforts by overweight individuals, not by average-weight teenage girls, w h o often diet aggressively and unwisely in pursuit of an ever-thinner ideal. Dieting clearly m a y contribute to eating disorders in these individuals, although it is not a sufficient cause of such complications, as reviewed by Wilson (1993). The term "dieting," as used here, refers to "the intentional and sustained restriction of caloric intake for the purpose of reducing body weight or changing body shape. The restriction of caloric intake results in significant negative energy balance" (National Task Force, 2000, p. 2582). The effects of dieting on psychological status m a y differ from those of restrained eating, a separate topic that is not discussed here (Lowe, 1993). Separating the effects of dieting from those of weight loss is also not discussed, since the two usually go hand in hand.
Effects of Dieting on Mood Concerns that dieting precipitates depression and other adverse emotional reactions resulted from two n o w classic reports. The first, from Minnesota, was an experiment in which normal-weight male volunteers reduced their initial body weight by 2 5 % during 6 months of marked caloric restriction (Keys, Brozek, Henschel, Mickelsen, & Taylor, 1950). This loss resulted in a body weight lower than that required for a diagnosis of anorexia nervosa (i.e., a weight > 1 5 % below normal), and the m e n displayed m a n y of the psychological symptoms of this disorder, including depressed m o o d , apathy, and preoccupation with food. Findings of this study are frequently used to warn of potential dangers of dieting in obese individuals. These findings, however, are more relevant to the experiences of averageweight teenage girls (who diet aggressively) than they are to obese adults w h o seek weight reduction. The second investigation found that 5 4 % of obese patients w h o were treated in a hos-
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pital nutrition clinic reported retrospectively that they had experienced symptoms of weakness, nervousness, irritability, or fatigue at some time w h e n previously dieting (Stunkard, 1957). These individuals did not report symptoms of depression, although the journal article that described thesefindingsw a s titled "The Dieting Depression." The tide was derived from observations of a second group of 25 individuals w h o were treated on an inpatient unit for both their psychiatric illness and obesity. Other early investigations, reviewed by Stunkard and Rush (1974), also reported negative emotional responses to dieting. In contrast to these early findings, numerous studies published in the past 25 years have reported reductions in symptoms of depression and anxiety—or, at a m i n i m u m , no worsening in affect—in obese patients w h o lost weight with behavior modification combined with a low-calorie diet (Taylor, Ferguson, & Reading, 1978; W a d d e n & Stunkard, 1986; Wing, Blah, Marcus, Epstein, & Harvey, 1994; Wing, Marcus, Epstein, & Kupfer, 1983), a very-low-calorie diet ( V L C D ) (Wadden, Foster, & Letizia, 1994; W a d d e n & Stunkard, 1986; W i n g et al., 1994; Wing, Marcus, Blah, & Burton, 1991), or weight loss medkations (BrowneU & Stunkard, 1981; Craighead, Stunkard, & O'Brien, 1981; W a d den, Vogt, et al., 1997). Several factors appear to explain the discrepancy between the early and later findings. Reports in the 1950s and 1960s were based principally on patients w h o had been referred to psychiatrists and were thus more likely to have had significant emotional disturbance prior to weight loss (SmoUer, W a d d e n , & Stunkard, 1987; Wing, Epstein, Marcus, & Kupfer, 1984). By contrast, more recent investigations, since 1975, have included obese individuals w h o volunteered specifically for weight reduction; a majority of these individuals are k n o w n to be free of clinically significant depression (Telch & Agras, 1994). In addition, most patients in the more recent studies received both group support and cognitive-behavioral therapy, each of which m a y favorably influence m o o d (SmoUer et al., 1987; W i n g et al., 1984). A review by SmoUer and colleagues (1987), showed that studies that included patients w h o were treated in behaviorally or medically oriented programs reported uniformly favorable changes in m o o d , whereas investigations of obese patients w h o received psychiatric care found uniformly negative outcomes. The difference in findings m a y also reflect differences in the frequency with which m o o d was assessed. Behavioral studies typically evaluated m o o d only before and after treatm e n t — a n assessment that m a y capture primarily the positive effects of losing weight, which often include looking and feeling better, receiving compliments from family and friends, or being able to wear fashionable clothing (SmoUer et al., 1987; W a d d e n , Stunkard, & SmoUer, 1986). M o r e frequent assessment, as included in early studies, m a y detect daily stresses and strains of dieting, which m a y include feeling hungry, having to monitor food intake, or missing out on food-related celebrations. A pilot study revealed partial support for this hypothesis (Wadden et al., 1986): A handful of patients reported chnically significant increases in dysphoria at some point while dieting, but m e a n depression scores were significantly below baseline at the end of the 26-week weight loss program. SmoUer and colleagues (1987) identified other methodological factors that appeared to account for the differences reported in early and later studies.
Clinical Issues The vast majority of findings indicate that obese individuals w h o lose weight are likely to experience improvements in m o o d . Improvements, however, are generally modest. As discussed previously, obese individuals w h o do not binge-eat usually score in the nondepressed range on the B D I and similar inventories. With weight loss they report even fewer symptoms of dysphoria, but such changes are probably not of clinical significance, given the normal baseline levels. Larger reductions in depression are likely to be observed in obese indi-
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Week FIGURE 8.2. Mean scores on the Beck Depression Inventory (BDI; Beck & Steer, 1987) of four groups classified on the basis of the Questionnaire on Eating and Weight Patterns ( Q E W P ; Spitzer et al., 1992). The four QEWP-derived groups were no overeating, episodic overeating (without a sense of loss of control), overeating plus a loss of control (subthreshold binge-eating disorder [BED]), and BED. From Gladis et al. (1998). Copyright 1998 by Elsevier Science. Reprinted by permission.
viduals with B E D , as shown, for example, by Gladis and colleagues (1998) (see Figure 8.2). In this study, obese patients with B E D improved from mildly depressed to essentially normal m o o d . Although dieting and weight loss appear to be associated with generally favorable changes in m o o d , practitioners should not conclude that weight reduction is an appropriate treatment for depression, anxiety, or related emotional complications in obese individuals. It is not, any more than it is with lean individuals. T h e approximately 1 0 % of obese patients w h o have clinically significant depression should receive professional attention before undertaking weight loss. Similarly, a small minority of obese individuals w h o seek weight reduction m a y need professional support during the course of losing weight. Rand, Kowalske and Kuldan (1984), for example, found that some patients left unsatisfactory marriages after losing weight with bariatric surgery. This ultimately m a y have been a positive step, but nonetheless a very stressful one. Similarly, in extremely obese w o m e n with a history of sexual abuse, weight loss has been reported to precipitate feelings of marked vulnerability and anxiety (Felitti, 1991). Such findings underscore the importance of practitioners' assessing patients' psychosocial status before and during weight loss, as reviewed by W a d d e n and Phelan in Chapter 10 of this volume.
Self-Directed Weight Loss Little is known about the psychological consequences of weight loss efforts undertaken outside of clinical trials. Specifically, what are the experiences of the mUlions of Americans w h o lose weight on their o w n using diet and/or exercise? Results of the National Weight Control Registry suggest that changes in m o o d in do-it-yourself dieters are similar to those in obese research patients (Klem, Wing, McGuire, Seagle, & HUI, 1997). T h e Registry consists of more than 1,000 individuals w h o have lost approximately 29.5 kg and maintained their weight losses for an average of 5.7 years. Approximately half of these individuals lost weight on their o w n , without professional assistance. Their scores (after losing weight) on measures
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of depression, distress, dietary disinhibition, and similar variables fell into essentially the mal range, suggesting that self-directed weight loss was not associated with adverse emotional responses. Further investigation is needed of weight loss efforts in the general population.
Effects of Dieting on Eating Disorders Dieting is considered a necessary precursor to the development of anorexia nervosa and bulimia nervosa (National Task Force, 2000; W U s o n , 1993). Its relationship, however, to the development of B E D — t h e eating disorder most frequently observed in obese individuals—is less clear (Stunkard, Chapter 6, this volume). Several studies found that approximately half of individuals with B E D reported that their pathological eating preceded their dieting, raising doubts as to whether dietary restraint is a prerequisite to binge eating (Berkowitz, Stunkard, & StaUings, 1993; Grilo & Masheb, 2000; SpurreU, Wilfley, Tanofsky, & BrowneU, 1997; Wilson, Nonas, & Rosenblum, 1993). Additional studies, reviewed below, revealed little influence of dieting in the development or exacerbation of binge eating. M o s t behavioral weight loss programs prescribe 1,000-1,500 kilocalories (kcal)/day for w o m e n and 1,500-1,800 kcal/day for m e n . Several studies found that this intervention was not associated with reports of binge eating in obese individuals w h o , before treatment, were classified as not binge-eating (Porzelius, Houston, Smith, Arfkin, & Fisher, 1995; Sherwood, Jeffery, & W i n g , 1999; W a d d e n et al., 1994). Moreover, numerous investigators observed significant reductions in binge eating during behavioral weight reduction in patients w h o were diagnosed with B E D prior to treatment (Agras et al., 1994; Marcus, Wing, & Fairburn, 1995; Porzelius et al., 1995). For example, the obese patients with B E D treated by Marcus and colleagues (1995) lost 9.9 kg during a 6-month program, and binge episodes decreased from 2 0 per m o n t h to approximately 2.7 per month. Although larger studies that include more males are needed, the evidence suggests that obese individuals w h o participate in traditional behavioral weight loss programs (i.e., with a diet of 1,000-1,900 kcal/day) are at minimal risk of developing binge eating. O n the contrary, such interventions appear likely to ameliorate binge eating, probably by helping patients adopt a more structured meal plan, increase their physical activity, or cope more effectively with food triggers and adverse emotions.
yery-low-Calorie Diets Some investigators as well as laypersons believe that V L C D s , which provide <800 kcal/day, present a significant risk of binge eating (O'NeiU, 1990; Polivy & H e r m a n , 1985). This belief is based in part on the results of the Minnesota study, in which m a n y of the weightreduced male volunteers engaged in binge eating following the termination of marked caloric restriction (Keys et al., 1950). T w o studies of obese individuals that examined this issue observed generally positive results. Yanovski and colleagues treated patients with a V L C D for 12 weeks and observed no significant increase in the frequency of reported binge days in persons w h o , before treatment, were classified as not binge-eating (Yanovski, Gormally, Lesser, Gwirtsman, & Yanovski, 1994; Yanovski & Sebring, 1994). In addition, there were no significant changes on the B E S (Gormally et al., 1982) 6 months after the V L C D . Patients w h o were diagnosed as binge-eating before treatment tended to report fewer binge episodes at the 6-month follow-up (p < .06), and their scores on the B E S declined significantly. W a d d e n and colleagues (1994) also reported reductions in symptoms of binge eating, as measured by this scale, foL lowing a 16-week liquid V L C D . The number of patients w h h severe binge eating decreased from nine to five.
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In contrast to these findings, Telch and Agras (1993) reported an increase in binge eating after 12 weeks' consumption of a liquid V L C D . Nearly 6 0 % of patients w h o at baseline had been classified as not binge-eating, reported occasional binge episodes in the 9 months following consumption of the V L C D . At afinalassessment, 12 months after severe caloric restriction, 1 5 % of these individuals met criteria for B E D . (Surprisingly, 3 9 % of patients w h o met criteria for B E D before treatment no longer did so at the final assessment.) These findings are cause for concern, but must be interpreted cautiously. Except for the baseline and final assessments, all measurements of binge eating were based on patients' self-reports, which are likely to overestimate the occurrence of binge episodes (see Stunkard, Chapter 6, this volume). This finding underscores the need to use uniform criteria in assessing binge eating. Data on the relationship between severe caloric restriction and binge eating are contradictory, and thus cannot provide definitive clinical guidance. Smith and W i n g (1991), for example, found no greater rate of reported dietary lapses in patients treated by moderate versus severe caloric restriction. In addition, patients with B E D generally lose as much weight on a V L C D as those w h o are free of this disorder (LaPorte, 1992; Telch & Agras, 1993; W a d d e n , Foster, & Letizia, 1992; Yanovski et al., 1994). Prudence, however, suggests not prescribing V L C D s to patients with a history of B E D or bulimia nervosa. Moreover, our research team has obtained excellent weight losses with the use of a 925-1,000 kcal/day diet that combines four servings a day of a nutritional supplement with an evening meal of a frozen food entree (Wadden, Vogt, et al., 1997). Patients treated by this diet reported few worries about resuming consumption of conventional foods after the period of marked caloric restriction. This is often a period of high anxiety w h e n a traditional liquid V L C D is used (Wadden & Bartlett, 1992).
Bariatric Surgery Concerns have also been expressed that surgical procedures for obesity, including vertical banded gastroplasty and gastric bypass, m a y precipitate eating disorders. Postoperative vomiting is a direct, involuntary consequence of gastric restriction and serves as a stimulus to reduce the amount consumed, as well as the consumption of certain items (e.g., steak) (Krai, 1998; Sugerman et al., 1992). Although h is aversive to patients, such vomiting is not comparable to that observed with bulimia nervosa or anorexia nervosa, in which patients report losing control of their food intake and then intentionally purging to prevent feared weight gain. Three studies found that approximately 2 5 % - 4 7 % of patients reported binge eating twice weekly or more before surgery (Adami, Gandolfo, Bauer, &c Scopinaro, 1995; Hsu, et al., 1996; Kalarchian, Wilson, Brolin, & Bradley, 1998). H s u and coUeagues (1996), for example, estimated that 3 7 % of their patients met criteria for B E D preoperatively. After surgery, none of their patients reported eating an unusually large amount of food in a discrete period of time, because their reduced stomach capacity prevented such overeating. Thus surgery appeared to ameliorate excessive eating, although 2 0 % of patients still reported subjective loss of control of their food intake, as they did prior to surgery. The few data available do not indicate that bariatric surgery is associated with the precipitation or exacerbation of eating disorders, although further study is required. Effects of Weight Loss on Body Image Several studies have reported improvements in body image in obese individuals who lost weight with behavioral treatment (Cash, 1994; Foster, W a d d e n , & Vogt, 1997; Rosen,
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Orosan, &C Reiter, 1995), as well as with bariatric surgery (Adami et al., 1998). Foster, W a d d e n , and Vogt (1997), for example, found that patients' scores on the Appearance Evaluation and Body Areas Satisfaction scales of the Multidimensional Body-Self Relations Questionnaire (Brown, Cash, & Mikulka, 1990) increased by a full standard deviation, bringing values to "normal." Surprisingly, larger losses were not associated with greater improvements in body image. This finding suggests the possibility of a weight loss threshold: Small losses m a y yield substantial improvements in body image, but no further improvements m a y occur with additional weight reduction. Alternatively, the finding suggests that factors other than weight (or weight loss), such as self-esteem or attributional style, m a y affect changes in body image. Rosen and colleagues (1995), for example, found that a cognitive-behavioral intervention that w a s designed to modify negative weight-related thoughts, but did not induce weight loss, produced significant improvements in body image—comparable to those produced by weight reduction. Studies have also s h o w n that body image dissatisfaction m a y persist despite weight loss. Cash and colleagues (1990) compared body dissatisfaction in normal-weight w o m e n without a history of obesity, currently normal-weight w o m e n with a history of obesity, and w o m e n w h o were currently overweight. Obese w o m e n reported a stronger drive for thinness, more negative body image affect (associated with weight and overall appearance\, more discrepant weight ideals, and higher anxiety while being weighed than did nonobese w o m e n without a history of obesity. However, normal-weight w o m e n with a history of obesity, compared with those without such a history, also reported significantly higher levels of body dissatisfaction, greater anxiety while being weighed, and a larger discrepancy between their current and ideal weights. A d a m i and coUeagues (1995) found that age of onset of obesity w a s a critical determinant of changes in body image satisfaction following bariatric surgery. After weight loss, the body image of individuals with adult-onset obesity did not differ from that of normal-weight controls. In contrast, those with early-onset obesity were significantly less satisfied with their weight and shape than were those with adult-onset obesity and normal-weight controls. The authors argued, simUar to Stunkard and Mendelson (1961), that body image crystaUizes during childhood and adolescence, and that persons with early-onset obesity m a y retain a negative internalized body image despite the reduction in their B M I to normal levels.
Effects of Weight Loss In Extremely Obese Individuals Improvements in /\Aood The most dramatic improvements in psychosocial functioning are likely to be observed in extremely obese individuals w h o undergo bariatric surgery. This is because, prior to surgery, they generally experience the most adverse psychosocial and physical consequences of obesity; thus they have the greatest potential for improvement. Solow, Siberfarg, and Swift (1974) described very favorable changes in their patients following bariatric surgery:
Previously housebound patients began to go out shopping; several took up athletic activities, and one even developed an enthusiasm for motorcycling A virtuous circle seemed operating here: as social withdrawal declined and social contacts developed, patients experienced novel positive feedback. Rather than feeling themselves objects of ridicule and contempt, they came to appreciate the respect and positive regard shown them. (p. 301) Positive changes in mood have been reported by others (Powers, Rosemurgy, Boyd, & Perez, 1997; Stunkard, Stinnett, & SmoUer, 1986; Waters et al., 1991). A s s h o w n in Figure 8.3, sur-
DejHcssirai
Anxiety
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F I G U R E 8.3. Participants in the Swedish Obese Subjects (SOS) study reported significantly greater decreases in depression and anxiety in the year after surgery than the controls. Circles, surgery patients; squares, controls. From Karlsson, Sjostrom, and Sullivan (1998). Copyright 1998 by Nature Publishing Group. Reprinted by permission.
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gically treated participants in the Swedish Obese Subjects (SOS) study, who lost appr mately 30 kg, reported significantly greater decreases in depression and anxiety in the year following surgery than did controls, w h o gained approximately 1 kg (Karisson et al., 1998). Improved Quality of Life
Improvements in mood are probably due to improved quality of life across a variety of cial and physical domains (Kushner & Foster, 2000). Participants in the SOS study, for example, reported marked increases in social interactions that had previously been adversely affected by their weight. Following weight loss, they were significantly less troubled than controls subjects by events such as going to restaurants or community activities, shopping for clothes, or being seen in a bathing suit. They also reported significantiy greater satisfaction with personal relationships. Choban, Onyejekwe, Burge, and Flancbaum (1999) observed simUarly favorable changes in patients w h o lost an average of 6 3 % of their excess weight following bariatric surgery. Before weight loss, patients scored lower than the national average on all scales of the SF-36 (Ware & Sherbourne, 1992) except Role Limitations due to Emotional Problems. Following surgery, their scores were comparable to national norms on the Role Limitations due to Physical Health Problems, Physical Functioning, General Mental Health, and General Health Perceptions scales of the SF-36 (Ware & Sherbourne, 1992). Their scores were higher than the national norms on the Social Functioning, Bodily Pain, and Vitality scales. Weight loss achieved with more traditional diet and exercise interventions is also associated with improvements in quality of hfe. Rippe and colleagues (1998) found that persons who lost 6.1 kg in 12 weeks by participating in a Weight Watchers program showed significantly greater improvements on the Physical Functioning, Role Limitations due to Physical Health Problems, and General Mental Health subscales of the SF-36 than controls w h o gained an average of 1.3 kg. Additional studies are needed of the effects of weight loss on quality of life in individuals w h o are not extremely obese and w h o are treated by traditional behavioral intervention. A central issue, discussed previously, will be determining the clinical significance of such changes. In this regard, it may be found that weight loss significantly enhances feelings of well-being. People may report feeling better physically and emotionally, even though they were not ill to begin with. This is the view of maximizing health, as compared with minimizing disease (Seligman & Csikszentmihalyi, 2000).
P S Y C H O S O C I A L EFFECTS O F W E I G H T LOSS A N D R E G A I N (WEIGHT CYCLING)
h is hard to imagine that the psychological effects of regaining lost weight are anyt negative. And unfortunately, a majority of people w h o lose weight typically return to their baseline weight within 3-5 years of completing treatment (Wadden, Sternberg, Letizia, Stunkard, & Foster, 1989). The behavioral consequences of weight cycUng have been reviewed by the National Task Force (2000), as well as by Foster, Sarwer, and Wadden (1997). Thus the main findings of this literature are only briefly summarized here.
Effects of Weight Cycling on Mood Several cross-sectional studies divided obese individuals into those with or without a history of weight cycling and compared them on mood, which was frequently assessed by the BDI (Bartlett, Wadden, & Vogt, 1996; Foreyt, Brunner, Goodrick, Cutter, &c BrowneU, 1995; Foster, Wadden, KendaU, Stunkard, & Vogt, 1996; Kuehnel & Wadden, 1994; Vendetti,
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Wing, Jakicic, Butier, & Marcus, 1996; Wadden, Bartlett, et al., 1992). The studies consistently found no significant differences in depression between subjects with and without a history of weight cycling. These investigations have been criticized because they did not assess differences in m o o d prior to weight loss and because they used varying definitions of weight cycling (Foster, Sarwer, & W a d d e n , 1997; Friedman, Schwartz, & Brownell, 1998). However, several prospective studies that foUowed patients through a cycle of weight loss and regain also failed to find adverse effects of weight cycling o n m o o d (BrowneU & Stunkard, 1981; Foster et al, 1996; W a d d e n , Sternberg, et al., 1989). T h e most thorough study, which examined patients w h o lost and regained 21.9 kg over a period of approximately 4 years, observed a m e a n B D I score of 9.3 at follow-up, compared with a score of 12.7 at baseline (Foster et al., 1996). Taken together, the results of cross-sectional and longitudinal studies indicate that weight cycling is not associated with clinically significant depression. It would be a mistake, however, to conclude that weight cycling does not have adverse emotional consequences. Patients evaluated by W a d d e n , Stunkard, and Liebschutz (1988) reported that weight regain had a moderately to very negative effect o n their satisfaction with appearance, selfesteem, and self-confidence. Weight cycling m a y affect dimensions of personal experience that simply are not assessed by standard depression scales. T h e generally positive findings reported here should not lead practitioners to minimize the shame and distress that so many patients report concerning their failed efforts to control their weight.
Relation of Weight Cycling to Binge Eating Cross-sectional studies have consistently found a positive relationship between weight cycling and binge eating (Bardett et al., 1996; Spitzer et al, 1992; Venditti et al., 1996; Yanovski & Sebring, 1994). Thus the greater the number of weight loss efforts, the greater the likelihood (or severity) of binge eating. These studies, however, cannot address the casual relation between these two variables. Rather than weight cycling causing binge eating, it is possible that binge eating leads to obesity, which is followed by efforts to lose weight and later to weight regain. In a thorough longitudinal investigation of this issue, Foster and colleagues (1996) observed reductions, rather than increases, in symptoms of binge eating in w o m e n w h o lost and regained 21.6 kg. Moreover, patients reported reductions in dietary disinhibition.
Clinical Implications of Findings Taken as a whole, the literature indicates that neither dieting nor weight cycling has serious adverse effects on the psychosocial functioning or eating habits of the great majority of overweight and obese individuals. Given the clear adverse health effects of excess weight, w e do not believe that obese individuals should be dissauded from trying to lose weight because of fears of negative behavioral consequences. There is, however, a clear and pressing need to identify n e w treatments that will confer long-term weight control, and thus spare obese individuals from the frustration and dismay that accompany weight cycling.
SUMMARY A N D CONCLUSIONS Obesity is an exceptionally heterogeneous disorder in terms of hs etiology, physical and behavioral presentation, and association with adverse health events. This heterogeneity is particularly evident w h e n one considers the psychosocial status of overweight and obese indi-
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viduals. The great majority of these persons appear to have essentially normal psychological functioning, despite their daily exposure to weight-related prejudice and discrimination in a society that glorifies thinness. A m o n g persons encountered in clinical settings, approximately 1 0 % - 2 0 % are likely to suffer from chnically significant symptoms of depression, negative body image, or impaired health-related quality of life. Such problems are most likely to occur in w o m e n (particularly from higher SES levels), in those with B E D , and in those with extreme obesity (i.e., B M I > 4 0 kg/m^) and its attendant health complications. Thus practitioners should be particularly sensitive to the emotional well-being of obese w o m e n w h o present with any of these additional risk factors. Practitioners, however, must balance the need for attentiveness with the equally important need not to stereotype their obese patients—not to attribute psychopathology or other shortcomings to them. T h e most satisfactory approach is to encourage patients to tell their o w n stories concerning h o w weight has affected their lives. M o s t welcome this opportunity. M o r e often than not, w e are impressed not by patients' emotional problems but by their resilient spirit and tenacious efforts to control their weight. These are the very qualities that should guide practitioners' care of their patients.
REFERENCES Adami, G. F., Gandolfo, P., Bauer, B., Sc Scopinaro, N. (1995). Binge eating in massively obese patients undergoing bariatric surgery. International Journal of Eating Disorders, 17, 45-50. Adami, G. P., Gandolfo, P., Campostano, A., MenegheUi, A., Ravera, G., Sc Scopinaro, N . (1998). Body image and body weight in obese patients. International Journal of Eating Disorders, 24, 299-306. Agras, W . S., Telch, C. F., Arnow, B., Eldredge, K. L., WUfley, D., Raeburn, S. D., Henderson, J., Sc Marnell, M . (1994). Weight loss, cognitive-behavioral, and desipramine treatments in binge eating disorder: A n additive design. Behavior Therapy, 25, 225-238. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, D C : Author. Averett, S., Si Korenman, S. (1996). The economic reality of the beauty myth. Journal of H u m a n Resources, 31, 304-329. Barofsky, L, Fontaine, K. R., Si Cheskin, L. J. (1998). Pain in the obese: Impact on health-related quality of Ufe. Annals of Behavioral Medicine, 19, 4 0 8 ^ 1 0 . Bartlett, S. J., Wadden, T. A., & Vogt, R. A. (1996). Psychosocial consequences of weight cycling. Journal of Consulting and Clinical Psychology, 64, 587-892. Beck, A. T., Si Steer, R. A. (1987). Manual for the Beck Depression Inventory. N e w York: Psychological Corporation. Berkowitz, R. I., Stunkard, A. J., & StaUings, V. A. (1993). Binge eating disorder in obese adolescent girls. Annals of the N e w York Academy of Sciences, 699, 200-296. Brewerton, T. D., O'NeU, P. M., Dansky, B. S., & Kilpatrick, D. G. (1999). Links between morbid obesity, victimization, PTSD, major depression, and bulimia in a national sample of women. Obesity Research, 7(Suppl.), 56S. Brody, M . L., Walsh, T., Sc Devlin, M . J. (1994). Binge eating disorder: ReliabUity and validity of a new diagnostic category. Journal of Consulting and Clinical Psychology, 62, 381-386. Brown, T. A., Cash, T. F., Sc Mikulka, P. J. (1990). Attitudinal body image assessment: Factor analysis of the Body-Self Relations Questionnaire. Journal ofPersonality Assessment, 55, 135-144. BrowneU, K. D., & Stunkard, A. J. (1981). Couples training, pharmacotherapy, and behavior therapy in the treatment of obesity. Archives of General Psychiatry, 38, 1224-1232. Brownell, K. D., & Wadden, T. A. (1991). The heterogeneity of obesity: Fitting treatments to individuals. Behavior Therapy, 22, 153-177. Canning, H., Si Mayer, J. (1966). Obesity: hs possible effects on college admissions. N e w England Journal of Medicine, 275, 1172-1174.
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A D U L T
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Patient
R I C H A R D L. A T K I N S O N
As recently as the past decade, obesity w a s not considered a medical Ulness, but instead was viewed as a behavioral disorder. However, obesity meets all of the clinical definitions of a disease. It has an organ, adipose tissue, that is dysfunctional. It produces multiple complications that lead to higher morbidity and mortality (Pi-Sunyer, 1993). T h e most recent estimates suggest that obesity contributes to more than 300,000 deaths per year in the United States (AUison, Fontaine, M a n s o n , Stevens, & VanltaUie, 1999). It is associated with hormonal and metabolic alterations, and treatment returns some of these toward normal (Drent, 1998). Research on the genetics of obesity provides explanations for some of the metabolic and hormonal differences between obese and nonobese individuals (Bouchard, Perusse, Rice, &; R a o , 1998). M o r e than 200 genes and gene markers have been identified that are implicated in h u m a n obesity (Chagnon, Perusse, Weisnagel, Rankinen, & Bouchard, 2000), and it is likely that m a n y more will be discovered. The implications of this research alone suggest that there m a y be dozens (or even hundreds) of different types of obesity, based on genetic variation. (For a fuller discussion of this topic, see Price, Chapter 4, this volume.) Recent research demonstrates that intrauterine and early postnatal factors m a y have a profound impact later in life on the development of obesity and weight-related complications, such as diabetes and hypertension (Silverman, Rizzo, C h o , & Metzger, 1998; Stanner et al., 1997; Strauss, 1997). Animal studies suggest that infectious agents m a y produce obesity (Carter, O w , & Smith, 1983; Dhurandhar, Israel, Kolesar, Cook, & Atkinson, 2000; Dhurandhar, Kulkarni, Ajinkya, & Sherikar, 1992; Dhurandhar, Kulkarni, Ajinkya, Sherikar, & Atkinson, 1997; Gosztonyi & Ludwig, 1995; Lyons et al., 1982), and the first human virus implicated in producing this disorder in animal models has been described (Dhurandhar et al., 2000, 2001). The realization that obesity is a medical Ulness demands that medical evaluation be carried out to identify the biochemical alterations in overweight patients. This is important, because the type of obesity m a y influence the decision of which treatment to initiate. This 173
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chapter describes the medical evaluation of obese patients who seek weight reduction. It is aimed at the practicing physician and attempts to provide a logical, stepwise progression in the medical evaluation, with special reference to complications associated with obesity. These complications m a y be overlooked in an examination that is not focused on obesity.
H I S T O R Y O F T H E PATIENT'S O B E S I T Y A thorough history is the most important part of the initial evaluation. This includes both the usual medical history and an evaluation of obesity-specific factors. Since obesity is the chief complaint, it is necessary to take a history of the patient's development of this disorder.
Onset and Progression of Obesity The clinician should ask w h e n the patient first become overweight or obese, and whether there were any events that might be implicated in the etiology, as discussed below. Changes in body weight over time, with weights at such milestones as puberty, high school or college graduation, pregnancy, or menopause, m a y give clues about the etiology. It is important to record the lifetime m a x i m u m weight, because if the patient is significantly below that weight, it m a y indicate that he or she is engaging in restrained eating and is maintaining a weight below the level that the body defends (i.e., the body weight set point). This m a y have implications for treatment, as described below. A history of events surrounding rapid weight gain or loss should be elicited. For females, prepregnancy weight and weight 6 months after delivery are useful. Fannily History of Obesity A family history of obesity provides an indication of the genetic contribution to the patient's obesity (Bray, 1998b). Also, a family history of comphcations such as diabetes, hypertension, heart disease, or stroke should prompt a careful evaluation for the presence of these in the patient. A family history of complications mandates educating patients about the signs and symptoms to which they should pay attention. It m a y also prompt more aggressive initial or long-term therapy.
ASSESSMENT OF THE ETIOLOGIES OF OBESITY Obesity may have many different etiologies. Decisions on treatment may be influenced by an understanding of the underlying mechanisms in the individual patient. Endocrine Dysfunction Endocrine dysfunction is among the most rare causes of obesity, but critically important, because treating the underlying disease m a y improve or resolve the obesity. The endocrine diseases associated with obesity are as follows: 1. Thyroid disease: Hyperthyroidism and hypothyroidism 2. Syndromes of excess insulin: Insulinoma, nesidioblastosis 3. Cushing's syndrome: Adrenocorticoid excess
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4. Polycystic ovary syndrome 5. Hypogonadism 6. Hypothalamic d a m a g e or disease 7. Growth h o r m o n e deficiency 8. Leptin deficiency or receptor defect 9. Pseudohypoparathyroidism Failure to diagnose an underlying endocrine disorder may have major implications for health and even survival. Research suggests that obese patients often suffer discrimination from health care professionals ( M a d d o x & Leiderman, 1969; Price, D e s m o n d , Krol, Snyder, & O'ConneU, 1987). Physical complaints that in a lean individual might be taken seriously are often ignored in obese patients. Complaints u n c o m m o n in obese people, such as documented hypoglycemia, bone fractures in younger individuals, or cold intolerance, m a y point to insulinoma, Cushing's syndrome, or hypothyroidism.
Genetic Background Single-gene defects as etiologies of obesity are exceedingly rare, but do occur (Bouchard et al., 1998; Chagnon et al., 2000). M o s t cases of obesity due to genetic factors are associated with multiple-gene defects or differences (Bouchard et al., 1998; Chagnon et al., 2000). W h e n a clinician is faced with a massively obese patient or an individual w h o is gaining weight very rapidly, particularly a child, genetic defects should be considered. Several syndromes of obesity are associated with specific findings, such as mental retardation, short stature, small hands and feet, hypogonadism, ophthalmic disorders, and voracious appetite (Bouchard et al., 1998). These include genetic or dysmorphic syndromes (e.g., Prader-Willi, Bardet-Biedl, Ahlstrom, Cohen, and Carpenter syndromes; see Bray, 1998a), as well as endocrine dysfunction sydromes. If there is a suspicion of a genetic disorder or a specific syndrome, referral to a specialist in obesity or pediatric obesity m a y be indicated. These patients are remarkably difficult to treat, and aggressive therapy, such as drugs or surgery, may be indicated.
Environmental Contributors to Obesity All obese individuals have had an imbalance in energy intake and expenditure during accumulation of their excess adiposity. Thus either intake has been excessive, or expenditure has been inadequate. Often obese patients will clearly identify their problem as an excessive intake or a very sedentary lifestyle. A careful evaluation of customary diet and physical activity patterns, as described below, m a y reveal these c o m m o n causes of excess energy balance. Ethnic or social identity m a y be associated with particular patterns of food intake or types of foods that enhance the likelihood of developing obesity (Kumanyika, 1987). A careful evaluation m a y reveal other factors or events that have contributed to obesity. S o m e severely obese people, particularly w o m e n , give a history of sexual abuse in childhood or adolescence that m a y have contributed to their weight gain; in such cases, the obesity serves either a protective or a comforting function (Felitti et al., 1998). Patients rarely volunteer this information, so it is important to inquire. Unresolved issues m a y require referral for psychological or psychiatric counseling. F e w individuals have any knowledge of their mothers' pregnancy histories, but malnutrition during pregnancy is k n o w n to produce obesity and other complications in the offspring (Silverman et al., 1998; Stanner et al., 1997; Strauss, 1997). Thus inquiries about this topic m a y be revealing. Low-birthweight and small-for-gestational-age babies have been
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shown to have a higher prevalence of obesity in later life (Forsen et al., 2000), so inquiries about birthweight m a y be helpful. A n increased prevalence of obesity after tonsillectomy (Lang, Sebok, & Katona, 1986) validates the anecdotal stories that m a n y patients teU of obesity's starting after a surgical procedure. Similar anecdotes about obesity's beginning after the "flu" or other infection gain credibility with the reports of obesity in animals due to infectious agents (Carter et al., 1983; Dhurandhar et al., 1992; Dhurandhar, 1992, 2000, 2001; Gosztonyi & Ludwig, 1995; Lyons et al., 1982).
A S S E S S M E N T O F W E I G H T L O S S E F F O R T S , DIET, A N D P H Y S I C A L ACTIVITY The clinician should inquire, for several reasons, about previous weight loss efforts. A history of repeated failure with diet and exercise therapy m a y be a justification for more aggressive treatment, or m a y require a more careful history to determine whether the programs were sufficiently comprehensive. M y o w n belief is that past failure in a comprehensive program predicts future failure. It m a y be necessary to proceed to pharmacological therapy, or even to obesity surgery if the patient qualifies for it. If a particular pharmacological agent has been used unsuccessfully in the past or with only modest effects, this m a y be an indication to start combination therapy. Other important aspects of past weight loss efforts are the occurrence of any complications, such as gout, gallbladder attack, bulimia, psychological or emotional problems, or other less frequent adverse events.
Current Efforts to Control Body Weight Often patients are already using weight control methods when they are evaluated by the clinician. It is important to k n o w not only about physician-directed treatments, but particularly about self-treatment with special diets, diet supplements, or over-the-counter (OTC) weight loss aids. A hst of the medications the patient takes is obviously needed, but often patients will not volunteer that they are taking O T C preparations unless specifically asked. O T C preparations with substances such as ephedra and caffeine, St. John's wort, or phenylpropanolamine should not be used with certain weight loss drugs. S o m e O T C preparations contain diuretics that m a y promote loss of potassium or magnesium, and m a y influence the selection of obesity medications or prompt careful attention to cardiac function and electrolyte concentrations. Fad diets that restrict or increase intake of individual nutrients, such as low-carbohydrate diets, high-protein diets, or very-low-calorie diets, need to be evaluated to determine the most appropriate treatment regimen. Dietary Assessment Although a physician should be able to obtain at least a cursory diet history, a careful assessment of dietary intake probably is best done by a dietitian. It is useful to have patients keep a 3-day food diary to ascertain theh customary intake, but since most individuals underestimate their calorie intake, and particularly theh fat intake, these diet records should be interpreted cautiously (Livingstone, 1995). Dietitians have experience in assessing the accuracy of diet records and are valuable coUeagues in the treatment of obese patients. The impact of the advent of the Internet on diet analysis programs has not been adequately evah uated. For intelligent and perceptive patients w h o are computer-literate, such programs m a y offer another option for obtaining a diet history. Physicians should note the daily intake of fat, protein, andfiber,as these are most often altered in dieting patients. It m a y be useful to pay particular attention to the consumption of fruits and vegetables, since high in-
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take of these foods is associated with a reduced risk of obesity, heart disease, strokes, and cancer.
Physical Activity Assessment Several studies have now shown that the level of daily physical activity correlates with body mass index (BMI) in the population and is critical for long-term weight maintenance (Coakley, R i m m , Colditz, Kawachi, & Willett, 1998; McGuire, Wing, Klem, Seagle, & Hill, 1998; Sarho-Lahteenkorva & Rissanen, 1998; Schoeller, Shay, & Kushner, 1997). M a n y obese people do not exercise and are not active in their daily lives. The reasons for this are unclear, but Sims and colleagues (1973) noted that overfed volunteers reduced their physical activity as they gained weight, so it is likely that this is a physiological response to increasing adiposity. There are suggestions that obese people are more sensitive to pain than are lean individuals (Pradalier, Dry, WUler, & Boureau, 1980), so perhaps exercise is more uncomfortable. Questions should be directed not only toward the amount and types of exercise that patients engage in each week, but toward their activities of daily living. Zurlo and colleagues (1992) and Levine, Eberhardt, and Jensen (1999) have shown that spontaneous physical activity or "fidgeting" is a source of significant energy expenditure and varies dramatically a m o n g individuals. A history of a very sedentary lifestyle m a y aher the treatment regimen prescribed. Since aerobic and resistance exercise produce different effects on body composition (Garrow & Summerbell, 1995; Walberg, 1989), h is useful to obtain a history of the types of exercise in which patients engage. Swimming produces good cardiovascular conditioning, but some studies suggest that it does not produce as m u c h weight loss as does weightbearing exercise (Garrow & SummerbeU, 1995; Gwinup, 1987; Walberg, 1989).
A S S E S S M E N T O F C O M P L I C A T I O N S O F OBESITY Obesity is associated with numerous health complications, as listed in Table 9.1. Patients may not be aware of these conditions or of their association with obesity. Complications that frequently go unrecognized by a patient are sleep apnea, diabetes melhtus, hypertension, gallbladder disease, gout, and hyperlipidemia. If these conditions are identified, coordination of their treatment with the patient's primary care physician is mandatory. If the condition is already k n o w n , the patient m a y be on medications. Since weight loss reduces or sometimes resolves some of these conditions, medication dose m a y need to be adjusted. With weight loss, patients m a y develop hypoglycemia on diabetes medications or hypotension on antihypertensives. Thus frequent assessment of blood glucose by h o m e glucose monitoring and of blood pressure is necessary. Sleep apnea deserves special mention, since h is c o m m o n in obese individuals and frequentiy is not recognized. The major symptoms include morning headache, daytime hypersomnolence, restless sleep, nightmares, nocturnal awakening with dyspnea, and dramatically loud snoring. Family members m a y give a history of apneic episodes if asked (GuiUeminauh, 1989; PhUlipson, 1993; Schwab, Goldberg, & Pack, 1998). A suspicious history for sleep apnea should prompt consideration of referral to a sleep laboratory for formal evaluation. Other complications seen c o m m o n l y in obese people that should be sought are a history of gastroesophageal reflux disease ( G E R D ) , urinary incontinence, sexual or reproductive dysfunction, symptoms of gout, and symptoms of the increased intra-abdominal pressure
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TABLE 9.1. Complications of Obesity 1. Diabetes mellitus, insulin resistance, 12. Urinary incontinence hyperinsulinemia 13. Reproductive dysfunction 2. Hypertension 14. Gout 3. Dyslipoproteinemia 15. Increased intra-abdominal pressure (lAP) 4. Heart disease: Atherosclerotic disease, congestive syndrome heart faUure 16. Pseudotumor cerebri 5. Cerebrovascular disease 17. Adiposis dolorosa (Dercum's disease) 6. Lung disease: Sleep apnea, restrictive lung disease 18. Pregnancy risks: Toxemia, diabetes 7. Cancer: Breast, uterus, colon, prostate, renal, others 19. Surgery risks: Pneumonia, wound infection, 8. Gallbladder disease: Stones, infection thrombophlebitis 9. Degenerative arthritis 20. Psychological and emotional problems 10. Venous stasis and edema 21. Social and economic problems 11. Gastroesophageal reflux disease (GERD) 22. Premature mortality
(lAP) syndrome (Sugerman, Bloomfield, & Saggi, 1999). Sugerman and coUeagues have published several studies of morbidly obese people that have documented the presence of increased lAP, which m a y include symptoms of hypertension, urinary incontinence, G E R D , headaches, increased intracranial pressure, and pseudotumor cerebri (Bloomfield, Ridings, Blocher, M a r m a r o u , & Sugerman, 1997; Sugerman, Bloomfield, & Saggi, 1999; Sugarman, Felton, Salvant, Sismanis, & K e U u m , 1995; Sugerman, Felton, et al., 1999). lAP responds very well to massive weight loss after gastric bypass surgery, so documentation of its presence is a strong indication for such treatment.
General Medical History Once the history of obesity and its complications has been obtained, a general medical history, appropriate for all patients, should be taken. The presence of other diseases (such as arthritis, fibromyalgia, neuropathy, and gastrointestinal disorders) m a y influence the diet, physical activity, or medication regimens prescribed. It is imperative to determine the medications the patient is taking, since there m a y be drug interactions with obesity drugs. Of particular note are drugs that affect the central nervous system (CNS), since this is the mechanism of action of most obesity drugs. The patient's use of antidepressant medications should be assessed. Fluoxetine and sertraline are associated with weight loss, at least over the short term (Goldstein & Potvin, 1994; Goldstein et al., 1993, 1995; W a d d e n et al., 1995). It m a y be useful to switch to these drugs (from the older noradrenergic agents) if the depression can be controlled with their use. Conversely, antidepressants that are selective serotonin reuptake inhibitors or adrenergic stimulating agents m a y preclude use of some of the obesity drugs, such as sibutramine, phentermine, or other C N S agents.
PHYSICAL EXAMINATION As with the history, there are features specific to obesity that should be assessed in the course of a complete physical examination.
Anthropometric Measurements Obesity is an excess of adipose tissue, and virtually all obese people also are overweight. On every patient, but particularly every obese patient, height and weight should be measured.
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Patients give inaccurate values for both height and weight, so self-reports are not sufficient. Assessment of body fat is better than simple height and weight, and there are simple to very complicated methods of assessing fat (PietrobeUi, W a n g , & Heymsfield, 1998), as discussed later. Perhaps the most global method of estimating body fat is with the B M I , which is calculated as weight in kilograms divided by height in meters squared. The B M I is highly correlated with measures of body fat and predicts both morbidity and mortality. Figure 9.1 aUows determination of B M I , based on the patient's height in inches and weight in pounds. According to the National Heart, Lung, and Blood Institute (1998; see also Table 18.2 in Aronne, Chapter 18, this volume), a B M I of 18.5-24.9 kg/m^ faUs in the "normal" range, w h U e persons with a B M I of 25.0-29.9 kg/m^ are considered "overweight." "Obesity" begins at a B M I of 30 kg/m^, with "extreme obesity" defined as a B M I > 40 kg/m^. The
BODY MASS INDEX (BMI) CHART
1
1
HEIGHT inches, meters! Inches 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 Meters 1.47 1.50 1.52 1.55 1.57 1.60 1.63 165 1.68 1.70 1,73 1.75 1.78 1.80 1.83 1.85 1.88 1.91 1.93 Pounds
Kq
100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 185 190 195 200 205 210 215 220 225 230 235 240 245 250 255 260 265 270 275 280 285 290 295 300 305
45.5 47.7 50.0 52.3 54.5 56.8 59.1 61.4 63.6 65.9 68.2 70.5 72.7 75.0 77.3 79.5 81.8 84.1 86.4 88 6 90.9 93.2 95.5 97.7 100.0 102.3 104.5 106.8 109.1 111.4 113.6 115.9 118.2 120.5 122.7 125.0 127 3 129.5 131 8 134 1
320 325
145 5 147.7
21 22 23 24 25 26 27 28 29 30 31 37 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 SO 51 52 53 54 56 57 SS 59 60 61 62 63 138 6 64
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 67 65 68 66
20 21 22 23 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64
19 20 21 22 23 24 25 26 27 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 44 45 46 47 48 49 50 51 57 S3 54 55 56 57 58 59 60 61 62
18 19 20 21 22 23 24 25 26 27 27 28 29 30 31 32 33 34 35 36 37 38 38 39 40 41 42 43 44 45 46 47 48 49 49 50 51 52 53 54 55 5R 57 58 59 60
18 19 20 20 21 22 23 24 25 26 27 28 28 29 30 31 32 33 34 35 36 36 37 38 39 40 41 42 43 43 44 45 46 47 48 49 50 51 51 52 53 54 55 56 57 58
17 IB 19 20 21 22 22 23 24 25 26 27 28 28 29 30 31 32 33 34 34 35 36 37 38 39 40 40 41 42 43 44 45 46 46 47 48 49 50 51 52 52 53 54 55 56
17 18 18 19 20 21 22 23 23 24 25 26 27 28 28 29 30 31 32 33 33 34 35 36 37 38 33 39 40 41 42 43 43 44 45 46 47 48 48 49 50 51 52 53 S3 54
16 17 18 19 19 20 21 22 23 23 24 25 26 27 27 28 29 30 31 32 32 33 34 35 36 36 37 38 39 40 40 41 42 43 44 44 45 46 47 48 49 49 50 51 52 53
16 16 17 18 19 20 20 21 22 23 24 24 25 26 27 27 28 29 30 31 31 32 33 34 35 35 36 37 38 38 39 40 41 42 42 43 44 45 46 46 47 48 49 49 50 51
15 16 17 16 18 19 20 21 21 22 23 24 24 25 26 27 27 28 29 30 30 31 32 33 34 34 35 36 37 37 38 39 40 40 41 42 43 43 44 45 46 46 47 48 49
15 16 16 17 18 18 19 20 21 21 22 23 24 24 25 26 27 27 28 29 30 30 31 32 33 33 34 35 36 36 37 38 38 39 40 41 41 42 43 44 44 45 46 47 47
14 15 16 17 17 18 19 19 20 21 22 22 23 24 24 25 26 27 27 28 29 29 30 31 32 32 33 34 35 35 36 37 37 38 39 40 40 41 42 42 43 44 45 45 46 50 1 48 47
FIGURE 9.1. Guide for cakulating body mass index (BMI), with a B M I obesity.
14 15 15 16 17 17 18 19 20 20 21 22 22 23 24 24 25 26 27 27 28 29 29 30 31 31 32 33 34 34 35 36 36 37 36 3S 39 40 41 41 42 43 43 44 45 46
14 14 15 16 16 17 18 18 19 20 20 21 22 22 23 24 24 25 26 27 27 28 29 29 30 31 31 32 33 33 34 35 35 35 37 37 38 39 39 40 41 41 42 43 43 44
13 14 15 15 16 17 17 18 19 19 20 20 21 22 22 23 24 24 25 25 26 27 28 28 29 30 30 31 32 32 33 34 34 35 36 36 37 38 38 39 40 40 41 42 42 43
13 14 14 15 15 16 17 17 18 19 19 20 21 21 22 23 23 24 24 25 26 26 27 28 28 29 30 30 31 32 32 33 33 34 35 35 36 37 37 38 39 39 40 41 41 42
13 13 14 14 15 16 16 17 18 18 19 19 20 21 21 22 23 23 24 24 25 26 26 27 28 28 29 29 30 31 31 32 33 33 34 34 35 36 36 37 38 38 39 39 40 41
12 13 13 14 15 15 16 16 17 IB 18 19 20 20 21 21 22 23 23 24 24 25 26 26 27 27 28 29 29 30 30 31 32 32 33 34 34 35 35 36 37 37 38 38 39 40
30 kg/m-^ considered as
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risks of health complications, including Type 2 diabetes, hypertension, and cardiovascular disease, increase with increasing obesity. In patients with a B M I of 25.0-34.9 kg/m^, risk is increased further by the presence of upper-body fat distribution. Upper-body fat is usually indicative of increased abdominal obesity, which is associated with increased morbidity and mortality (Pi-Sunyer, 1993). Body fat distribution m a y be estimated by the waist circumference, which should be measured at the iliac crest. Upper-body obesity is indicated in m e n by a waist circumference over 40 inches, and in w o m e n by a value over 35 inches. The waist-to-hip circumferences ratio has fallen out of favor and no longer is recommended as a tool for evaluating morbidity risk. Skinfold thickness m a y be measured with special calipers, but the accuracy and reproducibility in obese patients, particularly in massively obese individuals, is not adequate.
Specific Evaluation for Obesity-Related Complications A clinician performing a physical exam on an obese person should pay special attention to certain features. These include the impact of obesity on the patient's ability to walk, sit in a chair, or m o v e about. The e x a m should proceed from head to toe. First, the fundi should be examined for any evidence of increased intracranial pressure such as blurred disc margins or papilledema, which m a y be present in the increased intra-abdominal pressure syndrome. The mouth exam m a y reveal carious teeth due to increased sugar or soft drink consumption, or eroded teeth due to gastric acid exposure with bulimia. Also, the uvula and tonsils should be evaluated to see whether the airway is narrowed, as this m a y exacerbate sleep apnea. A careful thyroid exam is necessary, since 5 % or more of obese people will have an enlarged or nodular thyroid. Wheezing on examination of the lungs m a y signal obesityinduced asthma. Obese people are more susceptible to cardiac disease, including arrhythmias, so careful examination of the heart is mandatory (Bray, 1998b). For patients w h o have been on fenfluramine or dexfenfluramine, assessment of aortic or mitral regurgitation m a y be revealing. Breast cancer is more c o m m o n in obese w o m e n , so a breast e x a m should be methodical in covering the four quadrants of each breast (Pi-Sunyer, 1993). GaUbladder disease is m u c h more c o m m o n in obesity, so evaluation of abdominal pain or discomfort in the right upper quadrant should be performed. Thrombophlebitis is c o m m o n in obesity, so a calf e x a m should evaluate for Homan's sign. The presence of stasis changes of the lower legs and any edema should be noted. E d e m a is present in a large majority of patients with a B M I over 40 kg/m^. Since diabetes is c o m m o n in obesity, evaluation of the legs and feet for infection or skin lesions should be performed (Bray, 1998b; Pi-Sunyer, 1993). Adiposis dolorosa is an unusual syndrome that occurs in obesity and is almost always missed unless specifically sought (Atkinson, 1982). This syndrome is characterized by pain on palpation of subcutaneous fat. The pain m a y be very severe, and patients typically have sought increasingly potent analgesics without effect. It often occurs on the trunk, as abdominal pain, flank pain, or occasionaUy across-the-back pain. Pain in the fat pads around the knees is reportedly c o m m o n (Atkinson, 1982). I have seen three patients w h o had surgery or were scheduled for surgery (i.e., laparotomy, gallbladder surgery) and whose symptoms were due to adiposis dolorosa. This syndrome has a dramatic effect on quality of life, and most patients with it are miserable, particularly since theh physicians have usually dismissed them as having psychological problems. Adiposis dolorosa responds in a high percentage of cases to intravenous infusions of lidocaine (Petersen & Kastrup, 1987). Relief
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may be temporary, but with repeated infusions, many patients have permanent resolutio The etiology of this syndrome is unknown.
General Physical Exam
The remaining elements of a general physical exam should be performed in obese indivi als to identify other conditions that may have an impact on the treatment regimen selected.
L A B O R A T O R Y TEST A N D A S S E S S M E N T S O F B O D Y C O M P O S I T I O N Laboratory Tests
An extensive set of laboratory tests is recommended for the initial evaluation of obe tients, because so many different systems may be affected by obesity. A complete blood count (CBC) documents any anemia, but obese patients with sleep apnea may have polycythemia with an elevated hemoglobin level because of the chronic hypoxemia. A white blood cell differential analysis may uncover smoldering cholecystitis or cellulitis secondary to venous stasis. Electrolytes, calcium, and magnesium should also be checked, because obese people are more prone to cardiac arrhythmias. The presence of hypertension often mandates treatment with diuretics, which may alter results of these tests. Diet restriction, if severe, may also alter results of testing. Some obese patients have a high alcohol intake, which may alter electrolytes, magnesium, calcium, and phosphorus levels. Liver and renal function may be abnormal in obesity and should be checked. A blood glucose level and a lipid panel are mandatory because of the high frequency of abnormalities in obese individuals. A n elevated uric acid level should alert the physician to evaluate the patient for a history of gout and to follow the patient more closely during weight loss for any evidence of an acute attack of gout. Proteinuria, urinary tract infections, and renal cancer may occur in obesity, so a urinalysis is indicated. Because the prevalence of heart disease is more c o m m o n in obesity, an electrocardiogram is indicated, and if there are any symptoms, consideration should be given to performing a cardiac stress test before instituting an exercise program. The foUow-up laboratory assessment depends on the treatment regimen. Very-lowcalorie diets are not often used today, but additional lab tests are indicated in those cases (National Task Force on the Prevention and Treatment of Obesity, 1993). Since obese people, as noted, are at increased risk for diabetes, hypertension, cardiac disease, and gallbladder disease, tests that assess these problems should be performed during weight reduction. Rapid weight loss regimens require more tests, including electrolytes, liver function tests (to assess gallbladder disease), and electrocardiogram rhythm strips. A C B C every 3-6 months to check for anemia in food-restricted obese patients is advisable.
Methods of Assessing Body Composition Determination of body composition is becoming easier with the introduction of relatively inexpensive bioelectric impedance analysis (BIA) machines (PietrobeUi et al, 1998). BIA may be affected by a variety of factors, such as time from last meal, posture, and perhaps body habitus. Nevertheless, it may be a useful tool w h h which to follow changes in body composition with weight loss. The cost of dual-energy X-ray absorptiometry and of air displacement is falling with the introduction of these machines into more hospitals. Both give a better estimate of body composition than anthropometric measurements or BIA (PietrobeUi
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A S S E S S M E N T O F THE O B E S E ADULT
et al., 1998). Underwater weighing is available in some hospitals or research facilities, but is not generally available to the public. For selected patients at high risk for cardiac or vascular disease and diabetes, measurement of visceral fat m a y be helpful. Computerized tomography (CT) or magnetic resonance imaging ( M R I ) scans allow calculation of visceral fat (Pietrobelli et al., 1998). Single-cut C T across the fourth andfifthlumbar vertebrae is becoming a standard method of assessing visceral fat, and is relatively less expensive.
Assessment of Factors that Might Affect Obesity Treatment It is useful, upon completing the history and physical examination, for the clinician to reflect on the information learned that m a y affect the weight loss treatment prescribed. This is particularly true if other medical conditions, complications of obesity, or medications that m a y provoke drug interactions have been identified. Lack of any prior weight loss efforts m a y favor using less aggressive weight reduction regimens, such as conventional diet and exercise prescriptions. Conversely, repeated failure m a y prompt use of obesity drugs or surgery with appropriate individuals.
SUMMARY In summary, obesity is a disease of multiple etiologies. Careful attention to potential pathogenic factors, as well as to the possibility of obesity-related complications, is necessary during the medical evaluation of an obese person. Evaluation for c o m m o n complications, such as diabetes, hypertension, and cardiac disease, is part of every history and physical examination. Less c o m m o n conditions, such as sleep apnea, adiposis dolorosa, and increased intra-abdominal pressure syndrome, must be specifically evaluated w h e n one is seeing an obese patient. A wide assortment of laboratory tests m a y be justified because of the protean nature of the complications of obesity. Finally, specific laboratory tests to assess body fat or components of body fat, such as visceral fat, m a y be indicated for individual patients.
ACKNOWLEDGMENTS Preparation of this chapter was supported in part by funds from the Beers-Murphy Clinical Nutrition Center, University of Wisconsin-Madison, and by National Institutes of Health Grants N o . R 0 1 - D K 5 2 2 7 and N o . R 0 1 - D K 4 4 9 3 7 .
REFERENCES
AUison, D. B., Fontaine, K. R., Manson, J. E., Stevens, J., Si VanltaUie, T. B. (1999). Annual death attributable to obesity in the United States. Journal of the American Medical Association, 282(16), 1530-1538. Atkinson, R. L. (1982). Intravenous lidocaine for the treatment of intractable pain of adiposis dolorosa. International Journal of Obesity, 6, 351-357. Bloomfield, G. L., Ridings, P. C , Blocher, C. R., Marmarou, A., & Sugerman, H. J. (1997). A proposed relationship between increased intra-abdominal, intrathoracic, and intracranial pressure. Critical Care Medicine, 25, 496-503.
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Bouchard, C, Perusse, L., Rke, T., & Rao, D. C. (1998). The genetics of human obesity. In G. A. Bray, C. Bouchard, & W . P. T. James (Eds.), Handbook of obesity (pp. 157-190). N e w York: Marcel Dekker. Bray, G. A. (1998a). Classification and evaluation of the overweight patient. In G. A. Bray, C. Bouchard, Sc W . P. T. James (Eds.), Handbook of obesity (pp. 831-854). N e w York: Marcel Dekker. Bray, G. A. (1998b). Contemporary diagnosis and management of obesity. Newton, PA: Handbooks in Health Care. Carter, J. K., O w , C. L., & Smith, R. E. (1983). Rous-associated virus Type 7 induces a syndrome in chickens characterized by stunting and obesity. Infection and Immunity, 39, 410-422. Chagnon, Y. C , Perusse, L., Weisnagel, S. J., Rankinen, T., Si Bouchard, C. (2000). The human obesity gene map: The 1999 update. Obesity Research, 8, 89-117. Coakley, E. H., R i m m , E. B., Colditz, G , Kawachi, I., & WUlett, W . (1998). Predictors of weight change in men: Results from the Halth Professionals Follow-Up Study. International Journal of Obesity, 22, 89-96. Dhurandhar, N . V., Israel, B. A., Koksar, J. M., Cook, M . E., Si Atkinson, R. L. (2000). Increased adiposity in animals due to a human virus. International Journal of Obesity, 24, 989-996. Dhurandhar, N. V., Israel, B. A., Kolesar, J. M., Mayhew, G , Cook, M . E., & Atkinson, R. L. (2001). Transmissibility of adenovirus-induced adiposity in a chicken model. International Journal of Obesity, 25, 990-1006. Dhurandhar, N . V., Kulkarni, P. R., Ajinkya, S. M., Sc Sherikar, A. A. (1992). Effect of adenovirus infection on adiposity in chickens. Veterinary Microbiology, 31, 101-107. Dhurandhar, N. V., Kulkarni, P. R., Ajinkya, S. M., Shenkar, A. A., &; Atkinson, R. L. (1997). Association of adenovirus infection with human obesity. Obesity Research, 5, 464—469. Drent, M . L. (1998). Effects of obesity on endocrine function. In G. A. Bray, C. Bouchard, & W . P. T. James (Eds.), Handbook of obesity (pp. 753-773). N e w York: Marcel Dekker. Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., Koss, M . P., Sc Marks, J. S. (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. American Journal of Preventive Medicine, 14, 245-58. Forsen, T., Eriksson, J., TuomUehto, J., Reunanen, A., Osmond, C , & Barker, D. (2000). The fetal and childhood growth of persons w h o develop Type 2 diabetes. Annals of Internal Medicine, 133, 176-181. Garrow, G , Si SummerbeU, C. D. (1995). Meta-analysis: Effect of exercise, with or without dieting, on the body composition of overweight subjects. European Journal of Clinical Nutrition, 49, 1-10. Goldstein, D. J., & Potvin, J. H. (1994). Long-term weight loss: The effect of pharmacologic agents. American Journal of Clinical Nutrition, 60, 647-657. Goldstein, D. J., Rampey, A. H., Dornseif, B. E., Levine, L. R., Potvin, J. H., Si Fludzinski, L. A. (1993). Fluoxetine: A randomized clinical trial in the maintenance of weight loss. Obesity Research, 1, 92-98. Goldstein, D. J., Rampey, A. H., Roback, P. J., Wilson, M . G , Hamilton, S. H., Saykr, M . E., & ToUefson, G. D. (1995). Efficacy and safety of long-termfluoxetinetreatment of obesity: Maximizing success. Obesity Research, 3(Suppl. 4), 481S-490S. Gosztonyi, G , & Ludwig, H. (1995). Borna disease: Neuropathology and pathogenesis. Current Topics in Microbiology and Immunology, 190, 39-73. GuiUeminauh, C. (1989). Clinical features and evaluation of obstructive sleep apnea. In M . H. Kryger, T. Roth, & W . C. Dement (Eds.), Principles and practice of sleep medicine (pp. 667-677). Philadelphia: W . B. Saunders. Gwinup, G. (1987). Weight loss without dietary restriction: Efficacy of different forms of aerobic exercise. American Journal of Sports Medicine, 15, 275-279. Kumanyika, S. (1987). Obesity in black women. Epidemiologic Reviews, 9, 31-50. Lang, K., Sebok, A., & Katona, G. (1986). The role of tonsiUectomy in the development of childhood obesity- Orvosi Hetilap, 127(38), 2303-2305.
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Levine, J. A., Eberhardt, N. L., Sc Jensen, M. D. (1999). Role of nonexercise activity thermogenesis resistance to fat gain in humans. Science, 283(5399), 212-214. Livingstone, M . B. (1995). Assessment of food intakes: Are w e measuring what people eat? British Journal of Biomedical Science, 52, 58-67. Lyons, M . J., Faust, I. M., H e m m e s , R. B., Buskirk, D. R., Hirsch, J., Sc Zabnskie, J. B. (1982). A virally induced obesity syndrome in mice. Science, 216, 82-85. Maddox, G. L., Si Leiderman, V. (1969). Overweight as a social disabUity with medical implications. Journal of Medical Education, 44, 214-220. McGuire, M . T., Wing, R. R., K k m , M . L., & Hill, J. O. (1999). Behavioral strategies of individuals w h o have maintained long-term weight losses. Obesity Research, 7, 334-341. McGuire, M . T., Wing, R. R., K k m , M . L., Seagk, H. M., Si HiU, J. O. (1998). Long-term maintenance of weight loss: D o people w h o lose weight through various weight loss methods use different behaviors to maintain their weight? International Journal of Obesity, 22, 572-577. National Heart, Lung, and Blood, Institute. (1998). Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. Obesity Research, 6(Suppl.), 51S-210S. National Task Force on the Prevention and Treatment of Obesity. (1993). Very low calorie diets. Journal of the American Medical Association, 270, 967-974. Petersen, P., Sc Kastrup, J. (1987). Dercum's disease (adiposis dolorosa): Treatment of the severe pain with intravenous lidocaine. Pain, 28, 77-80. PhUlipson, E. A. (1993). Sleep apnea: A major public health problem. N e w England Journal of Medicine, 328, 1271-1273. Pi-Sunyer, F. X. (1993). Medical hazards of obesity. Annals of Internal Medicine, 119, 655-660. PietrobeUi, A., Wang, Z., Sc Heymsfield, S. B. (1998). Techniques used in measuring human body composition. Current Opinion in Clinical Nutrition and Metabolic Care, 1, 439-448. Pradalier, A., Dry, J., Wilier, J. C , Sc Boureau, F. (1980). Obesity and the nociceptive reflex. Pathologic Biologic, 28, 461-464. Price, J. H., Desmond, S. M., Krol, R. A., Snyder, F. F., Si O'ConneU, J. K. (1987). Family practice physicians' beliefs, attitudes, and practices regarding obesity. American Journal of Preventive Medicine, 3, 339-345. Sarlio-Lahteenkorva, S., Si Rissanen, A. (1998). Weight loss maintenance: Determinants of long-term success. Eating and Weight Disorders, 3, 131-135. Schoeller, D. A., Shay, K., & Kushner, R. F. (1997). H o w much physical activity is needed to minimize weight gain in previously obese women? American Journal of Clinical Nutrition, 66, 551-556. Schwab, R. J., Goldberg, A. N., & Pack, A. I. (1998). Skep apnea syndromes. In A. P. Fishman (Ed.), Fishman's pulmonary diseases and disorders (pp. 1617-1637). N e w York: McGraw-Hill. Silverman, B. L., Rizzo, T. A., Cho, N . H., & Metzger, B. E. (1998). Long-term effects of the intrauterine environment. Diabetes Care, 21 (Suppl. 2), 142-149. Sims, E. A. H., Danforth, E. Horton, E. S., Bray, G. A., Glennon, J. A., & Salans, L. B. (1973). Endocrine and metabolic effects of experimental obesity in main. Recent Progress in Hormone Research, 29, 457^96. Stanner, S. A., Bulmer, K., Andres, C , Lantseva, O. E., Borodina, V., Poteen, V. V., & Yudkin, J. S. (1997). Does malnutntion in utero determine diabetes and coronary heart disease in adulthood?: Results from the Leningrad siege study, a cross sectional study. British Medical Journal, 315(7119), 1342-1348. Strauss, R. S. (1997). Effects of the intrauterine environment on childhood growth. British Medical Bulletin, 53(1), 81-95. Sugerman, H. J., Bloomfield, G. L., Sc Saggi, B. W . (1999). Multisystem organ faUure secondary to increased intraabdominal pressure. Infection, 27(1), 61-66. Sugerman, H. J., Felton, W . L., Salvant, J. B., Sismanis, A., & Kellum, J. M . (1995). Effects of surgically induced weight loss on idiopathic intracranial hypertension in morbid obesity. Neurology, 45, 1655-1659. Sugerman, H. J., Felton, W . L., Sismanis, A., Kellum, J. M., DeMaria, E. J., & Sugerman, E. L
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(1999). Gastric surgery for pseudotumor cerebri associated with severe obesity. Annals of Surgery, 229, 634-640. Wadden, T. A., Bartlett, S. J., Foster, G. D., Greenstein, R. A., Wingate, B. J., Stunkard, A. J., & Letizia, K. A. (1995). Sertraline and relapse prevention training foUowing treatment by very-lowcalorie diet: A controlled clinical trial. Obesity Research, 3(6), 549-557. Walberg, J. (1989). Aerobic exercise and resistance weight-training during weight reduction: Implications for obese persons and athletes. Sports Medicine, 47, 343-356. Zurlo, F., Ferraro, R. T., FontvieUle, A. M., Rising, R., Bogardus, C , & Ravussin, E. (1992). Spontaneous physical activity and obesity: Cross-sectional and longitudinal studies in Pima Indians. American Journal of Physiology, 263, E296-E300.
1
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0
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Patient
T H O M A S A. W A D D E N S U Z A N N E PHELAN
The medical evaluation of an obese individual, described by Atkinson in Chapter 9 of this volume, should be complemented whenever possible by a behavioral assessment. Such an assessment is probably best conducted by a registered dietitian or mental health professional w h o specializes in obesity. Such personnel usually have more time to meet with patients than do primary care physicians. T h e goals of the assessment are to (1) obtain a fuller understanding of biological and behavioral factors that m a y contribute to a patient's obesity; (2) assess the psychosocial consequences of excess weight; and (3) examine the individual's goals and expectations for weight reduction (if it is desired). Another key objective is to provide patients an opportunity to discuss their personal experiences with their weight, and to have someone hsten attentively and respectfully. A s Stunkard (1993) has noted, "Such an experience m a y be the greatest gift that a doctor can give an obese patient; it compares favorably with the modest benefits of our programs of weight reduction" (p. 356). The assessment described in this chapter has been developed by our research team over the past 2 0 years. It is organized around five major points, summarized by the acronym " B E S T Treatment." B captures biological factors that m a y contribute to the patient's obesity, while E stands for environmental influences. S represents social/psychological status, and T describes the timing of the present weight loss effort. Following a review of these four components, patient and provider select the best Treatment option. Prior to their behavioral assessment, w e ask patients to complete the Beck Depression Inventory—II (BDI-II; Beck, Steer, & Brown, 1996) and the Weight and Lifestyle Inventory ( W A L I ; W a d d e n & Foster, 2001). T h e latter is a paper-and-pencU questionnaire that inquhes about the four areas described above. (The W A L I is included at the end of this chapter as Appendix 10.1.) T h e patient's completion of the these materials prior to the assessment allows the health care provider to identify the points of greatest interest and to focus the interview accordingly. T h e BDI-II has excellent reliability, as well as criterion and predictive validity (Beck et al., 1996). The items on the W A L I have acceptable reliability (Wad186
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den, Bartlett, et al., 1992). However, we have no data on the predictive validity of this inventory in, for example, identifying patients w h o will be successful with weight loss. Further research of this kind is needed. At present, the W A L I is intended only to elicit and organize information. M e m b e r s of our staff usually take 60 minutes to conduct the behavioral assessment, which makes it most appropriate for use in a specialty clinic. Primary care physicians, h o w ever, m a y want their patients to complete the questionnaires, which they can then quickly review for problem areas. Similarly, familiarity with the assessment will sensitize physicians to problems such as binge eating or dysthymic disorder, which are encountered in a significant minority of obese individuals.
INITIATING T H E I N T E R V I E W Practitioners frequently initiate weight reduction therapy without knowing the persons they plan to treat. Obesity m a y w e U be some individuals' most saUent attribute, but all people have other, more important characteristics that should be explored in the behavioral assessment. Thus the first 5-10 minutes of the interview should be devoted to getting to k n o w the patient. The interview should provide an overview of the patient's (1) intimate relationships (i.e., with parents, spouse/partner, children, and friends); (2) satisfaction with work and leisure activities; and (3) current life goals. F r o m the beginning, the practitioner should attempt to understand h o w weight affects and is affected by these factors, and what life changes the patient anticipates with weight loss. W e usually begin the assessment by thanking patients for completing the questionnaires and explaining that w e will review them to get a better sense of "your weight and dieting histories, eating and activity habits, and m o o d . W e will then discuss your desire to lose weight and the goals you hope to achieve. W e will finish by talking about treatment options." W e then talk with patients briefly about some aspect of their work or leisure activities before proceeding to review the questionnaire items. W e select what appears to be a conflict-free topic that a patient can discuss comfortably. For instance, w e might remark, "I read you are a teacher. W h e r e do you teach?" Although this discussion m a y resemble social chit-chat, it provides an opportunity to learn about the patient's satisfaction with work and the degree of stress associated with it. It also provides an opportunity to assess the patient's m o o d and verbal behavior, particularly if the patient is going to participate in a group program.
Primary Care Practice Primary care physicians will probably need to take a different approach to discussing weight, given that they already k n o w the patient. The question is h o w best to broach the topic of weight control with overweight individuals w h o have not asked for assistance. Statements such as "We've got to do something about your weight," or "If you don't lose some weight, you're going to have a heart attack," m a y be well intended but are likely to be off-putting, if not offensive. A more effective statement might be something like this: " W e have not talked about your weight in a while. W h a t are your thoughts about your weight at this time?" This open-ended question invites patients to discuss their possible concerns, rather than admonishing them that they should be concerned. Another option is to s u m m a rize the results of the physical examination to include a discussion of weight control. The practitioner might state, "Your blood pressure today was 146/90 m m H g , and your weight was 215 pounds. Y o u k n o w , I bet you could bring your blood pressure into the normal
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range by losing just 10 to 15 pounds. Would you like to consider this?" These approaches show respect for the patient and underscore the importance of inviting the individual's participation in treatment.
Reviewing BEST Treatment In this chapter, w e review biological, environmental, social, and timing factors in that order (the same in which they are assessed by the W A L I ) , and then discuss the selection of the best treatment option. Practitioners, however, m a y cover the " B E S T " items however they wish, particularly if a patient is eager to discuss a particular topic at the outset of the interview.
BIOLOGICAL F A C T O R S Classification The National Heart, Lung, and Blood Institute ( N H L B I , 1998) guidelines, reviewed by Atkinson in Chapter 9 of this volume, classify patients into different categories of overweight and obesity based on body mass index (BMI). In addition, the waist circumference m a y be used to assess whether the individual has upper-body fat distribution. These two simple measures provide an estimate of the patient's risk of weight-related health complications.
Fat Cell Size and Number Body weight also provides a rough estimate of whether a patient's obesity is characterized by an increase in fat cell size (hypertrophic obesity), by an increase in fat cell number (hyperplastic obesity), or by both. Fat cell weight in nonobese individuals is approximately 0.4-0.5 p,g, but with weight gain it m a y reach 1.0-1.2 |xg (Bjorntorp, 1975). Once ceUs reach this latter size, additional weight gain appears to result in an increase in fat cell number. Thus, w h e n an individual achieves a fat mass approximately twice the normal size, the likelihood of hyperplastic obesity increases significantly. A s shown in Figure 10.1, the greater the excess weight (and fat), the greater the hyperplasia. A n average-weight person has about 25-35 biUion fat ceUs (Leibel, Berry, & Hirsch, 1983), whereas a person with a body mass index > 40 kg/m^ m a y have as m a n y as 100-150 biUion ceUs (Leibel et al., 1983; Sjostrom, 1980). Persons with hypertrophic obesity alone have a reasonable prognosis for reaching "average" weight because ceU hypertrophy is reversible (Krotkiewski et al., 1977). By contrast, fat cell number does not appear to be reversible (Naslun, Hallgreen, & Sjostrom, 1988). Thus, even with weight reduction (achieved by reducing cell hypertrophy), patients with severe, hyperplastic obesity are likely to have two to three times the normal number of fat cells and a fat mass that is increased by the same proportion. These patients appear to stop losing weight w h e n they achieve normal fat cell size, even though they m a y remain 5 0 % or more overweight (because of their increased ceU number) (Bjorntorp et al., 1975; Krotkiewski et al., 1977). This finding appears to explain w h y extremely obese patients do not achieve statistically average weight, even w h e n treated with bariatric surgery. Fat ceU size and number can only be measured in research settings. CeU number, however, can be estimated from the data in Figure 10.1. Patients suspected of having hyperplastic obesity can be informed that there m a y be limits to their weight loss.
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_ NO 0, O X 0) i3 E 1
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• 50
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. 150
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7o Ideal Body Weight FIGURE 10.1. The relationship between fat cell number (in billions) and percent of ideal body weight (as determined by the 1959 Metropolitan Life Insurance Co. height and weight tables). I, II, and III refer to three groups of subjects with increasing severity of obesity. N O refers to nonobese subjects. From Leibel, Berry, and Hirsch (1983). Copyright 1983 by Raven Press. Reprinted by permission.
Genetic Factors As reviewed by Price in Chapter 4 of this volume, family and adoption studies suggest that genetic factors account for an estimated 2 0 % - 4 0 % of the variance in body weight. Estimates from some twin studies are even higher, reaching 7 0 % (AUison et al., 1996; Stunkard, Harris, Pederson, & McClearn, 1990). Body fat distribution also appears to be heritable (Bouchard, 1995; Bouchard, Despres, &C Mauriege, 1993). The specific genes that contribute to c o m m o n forms of h u m a n obesity have yet to be identified, and there are likely to be dozens, if not hundreds, that interact (Price, Chapter 4). A defect in a single gene, leptin, is sufficient to produce obesity in humans, but only a handful of such cases have been identified worldwide (Montague et al., 1997; Strobe, Issad, Camoin, Ozata, &c Strosberg, 1997). Other genes m a y influence resting energy expenditure (Argyropoulos, B r o w n , & WiUi, 1998; Bogardus, LiUioja, Ravussin, & Abbott, 1986; Bouchard et al., 1989), dietary-induced thermogenesis (Bouchard et al., 1990), and metabolic responses to overfeeding (Bouchard et al., 1990). Currently, there are not adequate methods to assess an individual's genetic predisposition to obesity. However, several factors are likely to suggest an increased role of biological as compared to environmental influences in the etiology of obesity. These variables can be assessed by obtaining a detailed weight and dieting history: 1. Age of onset of obesity. Childhood onset and adolescent onset of obesity are generally associated with greater body weight as an adult and with increased fat cell number (Bjorntorp, 1975; Sjostrom, 1980). In addition, onset of obesity by age 10 w a s found in one study to be associated with an increased relative risk of this condition in adult first-degree relatives (Price et al., 1990). Childhood onset doubles the risk of obesity in adulthood (Ser-
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dula et al., 1993), and the risk increases further if an individual is obese as an adolescent (Guo, Roche, Chumlea, Gardner, & Siervogel, 1994; Whitaker, Wright, Pepe, Seidel, & Dietz, 1997). Age of onset can be assessed by taking a careful weight history, as captured by items Bl and B6 of the W A L I (i.e., section B of the W A L I , items 1 and 6). Persons with childhood or adolescent onset of their obesity can lose large amounts of weight but are unlikely to reach statistically average weight, as noted previously. 2. Family history. A family history of obesity also appears to be a marker for a biological predisposition. A s noted, obesity runs in families, and it is n o w clear that this is due in part to shared genetic characteristics (Stunkard et al., 1986). Obesity in one parent more than doubles the risk that a child wUl be obese as an adult (Whitaker et al., 1997); the risk is even greater if both parents are obese (Lake, Power, & Cole, 1997; Whitaker et al., 1997). The strongest predictor of adult obesity is the combination of childhood or adolescent onset with a family history of obesity; 7 0 % - 7 5 % of children with these two risk factors become obese as adults. Maternal obesity appears to be a stronger risk factor than paternal obesity (Hashimoto, Kawasaki, Kikuchi, Takahashi, & Uchiyama, 1995; Mafeis, Talamini, & Tato, 1998; Noble, 1997). Family history m a y be assessed by obtaining a patient's reports of the weights and heights of his or her mother, father, and siblings (items 0 1 and C 2 of the W A L I ) . Weights of maternal and paternal grandparents should also be assessed. The use of silhouettes, included in the W A L I , helps to confirm the presence of overweight and obesity in relatives. 3. Weight loss history. Obese individuals w h o regain weight rapidly after treatment are likely to have increased fat cell number (Krotkieweski et al., 1977; Sjostrom, 1980). S o m e investigators have also suggested that weight cycling is a marker of an elevated body weight set point; weight loss is quickly reversed by compensatory biological mechanisms (including reductions in leptin and in resting and nonresting energy expenditure) that serve to restore weight to pretreatment levels (Keesey, 1986; Stunkard, 1982). Regardless of whether a history of weight cycling is a marker for a biological predisposition to obesity, before prescribing yet another course of treatment, the practitioner will want to k n o w what weight loss methods the patient has tried. Weight loss history m a y be assessed by item El of the W A L I , which inquires about the number of diets that resulted in a weight loss of 10 pounds (4.2 kg) or more. This method has adequate reliabUity (Wadden, Bartlett, et al., 1992). Patients in one of our studies reported an average of 4.9 ± 0.5 weight loss efforts, with a cumulative loss of 55.9 ± 6.0 kg (Wadden, Bartlett, et al., 1992). This careful analysis revealed that most persons had not lost and regained hundreds of pounds, despite frequent anecdotal reports to this effect. Summarizing the Role of Biological Factors
Some patients wUl present histories that clearly suggest a biological (i.e., genetic) predisposition to obesity, but other cases wiU be less clear. For example, a patient with a B M I of 40 kg/m^, childhood onset of obesity, and a positive family history is likely to have hyperplastic obesity and a genetic predisposition to this disorder. The presence of a biological predisposition is harder to judge in a male with a B M I of 40 kg/m^ w h o became obese as an aduh; has lost and regained weight only once; and, as a result of adoption, k n o w s nothing about the weights of his biological parents. At least three issues should be discussed with patients in w h o m a marked biologkal predisposition to obesity is suspected. Thefirstis that even though obesity is a heritable disorder, it is not inherited in the same manner as eye color (in which a person is born with blue, green, or brown eyes, with little influence of the envhonment). By contrast, genes
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probably confer the potential for obesity, but it is the environment that determines whether and the extent to which this potential is realized. A s G. A. Bray (personal communication, 1997) has stated, "Genes load the gun; the environment pulls the trigger." A second point is that by changing their personal environment—their eating and activity habits—patients can lose weight, even if they cannot achieve a statistically average weight. Third, information about biological contributions to obesity can be used to assuage the feehngs of guilt and shame that so burden some patients. Studies such as that by Bouchard and colleagues (1990) have s h o w n clearly that some persons gain more weight than others w h e n overfed by the same number of calories. This finding resonates with the experiences of m a n y obese people, w h o are perplexed by their body weight w h e n they compare their eating and activity habits with those of lean friends. The message here is that patients are not to blame for their excess weight, even though they are still responsible for adopting healthier eating and activity habits.
ENVIRONMENTAL
FACTORS
Environmental factors are clearly more responsible than genetic influences for the increased prevalence of obesity observed in industrialized nations in the past 10-20 years (Horgen & Brownell, Chapter 5, this volume). This makes it imperative to assess eating and activity habits to determine their possible contribution to a patient's obesity. Such an assessment will also reveal areas for intervention. This portion of the assessment should provide a sketch of the patient's daily eating pattern, approximate calorie intake, problem eating, and physical activity. Assessment of these variables typically continues throughout treatment.
Food Intake Number of /Aeals and Snacks a Day A key task is to determine the number of meals and snacks the patient consumes each day (as covered by item H 2 of the W A L I ) . This includes assessing w h e n meals and snacks are consumed and evaluating the consistency of the meal pattern. Individuals w h o skip meals (Schlundt, Hill, Sbrocco, Pope-Cordle, & Kasser, 1990) or have highly variable eating patterns (Roger, 1999) report greater hunger and disinhibition. A principal goal of treatment is to establish a structured meal plan.
Calorie Intake A rough estimate of the patient's calorie intake can be obtained by reviewing food intake for a typical weekday and a typical weekend day (see section I of the W A L I ) . The goal is to determine whether the patient's calorie intake is consistent with elevated body weight or is reportedly lower than would be expected. (Formulas for estimating energy requirements are provided by Melanson and D w y e r in Chapter 12 of this volume.) W e also frequentiy ask, "Do you think you eat the same amount as people of average weight, more than such people, or less than people of average weight?" Patients w h o report, usually with embarrassment, that they eat large amounts of food (or have a high calorie intake) can be told that this is actually good news, because treatment can help them reduce their intake. By contrast, persons w h o report an unexpectedly low energy intake should be told that it is difficuh to count portion sizes and to keep track of calories. This statement is based on the results of studies with doubly labeled water, which have shown that obese individuals typically un-
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derestimate their calorie intake by 30%-50%; nonobese individuals underestimate by approximately 2 0 % (Lichtman et al., 1992; SchoeUer, 1988, 1995; Schoeller & Field, 1991). Doubly labeled water is the preferred method of assessing energy requirements, but is too expensive for use in clinical care practice.
Diet Composition The composition of the diet can also be estimated by examining a typical weekday and weekend day, as well as the patient's favorite foods. The goal again is to determine (in broad terms) whether the patient eats a high-fat diet, or instead one that is consistent with the Food Guide Pyramid (Agricultural Research Service, 1995). A useful starting point for intervention is to determine h o w m a n y fruits and vegetables the individual consumes a day, and to increase this number gradually to at least five a day. Alcohol intake should also be assessed, (i.e., item G 3 ) , given the effects of alcohol consumption on dietary disinhibition and overall energy intake (Melanson & Dwyer, Chapter 12, this volume). Diet composition can be assessed more fully by a registered dietitian or by the use of a food frequency questionnaire, such as that developed by Block, W o o d s , Potosky, and Clifford (1990). The questionnaire by Block and colleagues is easily administered and can be machine-scored for a fee. Readers should k n o w that no measure of dietary intake has fully adequate reliabUity or vahdity (Melanson & Dwyer, Chapter 12). The behavioral assessment can provide only an impression of the patient's food intake that can be further refined during treatment.
Environmental Cues For some individuals, eating is strongly influenced by environmental cues, including times, people, places, emotions, and activities (BrowneU, 2000; Schlundt et al., 1990). Practitioners should attempt to identify cues that are reliably associated with overeating. Environmental cues are covered by item H I (L-X) of the W A L I , but should also be assessed on an ongoing basis during treatment.
Appetite Many individuals who binge-eat report that they overeat because of emotional distress. S o m e individuals w h o do not binge-eat, however, also report eating large amounts of food, principally because they have trouble feeling full at mealtimes. Such individuals appear to have impaired satiation, a problem that m a y be treated by behavioral intervention, but also by pharmacological agents such as sibutramine (Hansen, Toubro, Stock, Macdonald, & Astrup, 1999). Similarly, it is useful to determine whether the individual reports significant hunger or cravings and, if so, what times and places are associated with these events. These variables are assessed by item H I (G-J) of the W A L I , as well as by the Eating Inventory (Stunkard & Messick, 1988). Problem Eating As reviewed by Stunkard in Chapter 6 of this volume, as many as 30%, of participants who seek weight reduction report significant symptoms of binge eating, and 1 0 % - 1 5 % meet criteria for binge-eating disorder (BED) as confirmed by a diagnostic interview. B E D is characterized by the consumption of an objectively large amount of food in a short period of time
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(2 hours) with an accompanying subjective loss of control (Spitzer et al, 1992). Individuals with B E D are more likely to report symptoms of depression and other psychopathology (Marcus, W i n g , & Hopkins, 1988; Sherwood, Jeffery, & Wing, 1999; Spitzer et al., 1992, 1993; Telch & Agras, 1994; W a d d e n , Foster, Letizia, & W U k , 1993). Binge eating can be assessed by the Questionnaire on Eating and Weight PatternsRevised ( Q E W P - R ; Spitzer et al., 1992; Yanovski, 1993), which is easily administered and provides decision rules for diagnosing B E D , bulimia nervosa, and related eating disorders. (The Q E W P - R is included in the W A L I in items J1-J17.) The practitioner should confirm reports of binge eating by having patients describe two or more recent binge episodes, to determine that they ate an objectively large amount of food and experienced loss of control. As Stunkard (Chapter 6, this volume) has noted, however, if B E D is present, the patient's m o o d disturbance m a y be more significant in planning treatment than is the binge eating. Most studies have found no differences in weight loss between obese individuals with and without B E D (Gladis et al., 1998; Sherwood et al., 1999; W a d d e n , Foster, & Letizia, 1992). In addition, binge-eating episodes decline quickly with the introduction of a structured diet (Stunkard, Chapter 6). Symptoms of night-eating syndrome are assessed by section K of the W A L I . This eating pattern w a s first described by Stunkard, Grace, and Wolff (1955) almost 50 years ago. Studies are being conducted to define better its principal characteristics, prevalence, and etiology.
Physical Activity The increased prevalence of obesity has been paralleled by the proliferation of energysaving devices, including automobiles, televisions, computers, and remote control devices (HiU & Melanson, 1999; HUI, Wyatt, & Melanson, 2000; Prentice & Jebb, 1995; Weinsier, Hunter, Heini, Goran, &c SeU, 1998). Sedentary behavior is n o w a recognizedriskfactor for cardiovascular disease (Ravussin et al., 1997) and is significantly related to increased weight (BrowneU, 1995). Increased physical activity is not only the single best predictor of the maintenance of weight loss (Pronk & Wing, 1994); as reviewed by Blair and Leermakers in Chapter 13 of this volume, it appears to decrease the risk of morbidity and mortality, independently of weight loss. The goal in assessing physical activity is to locate patients on a continuum that ranges from "couch potato" to "marathon athlete." This can be done by inquiring about general level of daily activity, including number of blocks walked,flightsof stairs climbed, and hours of television watched. This provides an estimate of the individual's lifestyle activity (Andersen et al., 1999). Programmed or purposeful activity can be assessed by inquiring about the patient's frequency of walking (or jogging) and participation in other aerobic or anaerobic activities. Physical activity is covered by items L1-L9 of the W A L I . M o r e formal assessment of physical activity is provided by the Physical Activity RecaU, which is available in both questionnaire and interview versions (Blair, 1984). This instrument assesses occupational and leisure activities over the previous 7 days and categorizes activities by their intensity. The instrument has acceptable test-retest reliability (Blair, 1984). Alternatively, the Paffenbarger Physical Activity Questionnaire is a one-page inventory that assesses habitual daily and weekly activity (Paffenbarger, Wing, & Hyde, 1978). Informal assessment reveals that most of our patients are very sedentary. Their physical activity ofi:en consists of littie more than getting into the car to drive to work, the mall, or the supermarket. W h e n patients report with shame or chagrin that they are "couch pota-
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toes," we respond that this is a favorable, not a negative, finding. If they were already exercising vigorously, 6 days a week, w e would have little to offer them. In addition to assessing current physical activity, w e also inquire about exercise preferences. This includes the preferred type of activity (i.e., walking, swimming, aerobics, etc.), as well as whether the individual prefers to exercise alone or with others. Barriers that prevent the patient from exercising regularly should be determined (Blair & Leermaker, Chapter 13, this volume; Ravussin, 1995). For those w h o report that they simply hate to exercise, w e respond that the patients must have been fans of Sir Winston Churchill, w h o is said to have remarked, "Whenever I get the urge to exercise, I sit d o w n until it passes." This joke provides an opportunity to dispel myths about exercise. A c o m m o n belief is that physical activity must be vigorous in order to improve weight or health. Recent findings, however, indicate that moderate physical activity (equivalent to a brisk walk) is sufficient to improve cardiovascular health (Blair et al., 1989; Blair & Leermakers, Chapter 13, this volume; Y o u n g & Macdonald, 1992). Obese individuals similarly welcome news that increased lifestyle activity—which consists of increasing physical activity throughout the day, without regard to intensity—is as effective as programmed activity in inducing and maintaining weight loss (Andersen et al., 1999; Epstein, Wing, Koeske, & Valoski, 1985). Practitioners should emphasize that any increase in physical activity can improve weight and fitness, as can efforts to decrease sedentary activities such as watching television or playing computer games.
Summarizing the Role of Environmental (Behavioral) Factors This section of the interview concludes with a brief summary of the extent to which dietary intake and physical activity appear to contribute to the patient's weight problem. Clearly, this assessment is impressionistic; in most cases, however, the practitioner can determine whether there is opportunity to modify the patient's food intake, physical activity, or both. A worse-case scenario is a w o m a n w h o reports that she eats 1,200 kilocalories (kcal)/day (as recorded in her daily food record), walks 6 days a week (for 60 minutes per bout), and has a B M I of 35 kg/m^. Treatment would probably focus on ensuring the accuracy of her reported food intake and perhaps changing the composition of the diet. Otherwise, there appears to be little r o o m for behavioral intervention. By contrast, a w o m a n w h o reports that she is very sedentary and eats excessively in the evening presents multiple opportunities for behavior change. W e usually summarize findings in the following manner: " Y o u indicated that you hate to exercise and are very sedentary. In some ways, I'm glad to hear that. If you were already running marathons, w e wouldn't have any room for improvement. In terms of your eating habits, you said that you do not overeat at meahime, but have trouble snacking after dinner while watching television. Sometimes you eat as late as 11:00 p.m. untU the news comes on. We'll need to determine h o w m a n y calories you consume in this fashion and find ways to help you control your evening snacking."
SOCIAL/PSYCHOLOGICAL FACTORS This component of the assessment inquires about the patient's living arrangements, satisfaction with personal relationships, and expected social support w h e n attempting to lose weight (see section M of the W A L I ) . The patient's m o o d and psychosocial status should also be evaluated. The psychosocial assessment should address several topics.
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Social Context of Weight Loss • "What is the social context in which the patient will lose weight?" Weight loss does not occur in a vacuum. T h e weights, eating habits, and attitudes of a patient's family m e m bers, friends, and coworkers are likely to affect weight control efforts. W e frequently ask, "What did your partner [or friends] do that helped you lose weight the last time you tried? W h a t did your partner [or friends] do that hindered your weight control efforts?" The practitioner and patient m a y want to invite family members to a session if they are identified as significant barriers to weight control.
Psychosocial Effects of Obesity • "What effect does weight have on the patient's social functioning, self-esteem, body image, and general quality of life?" Overweight and obese individuals are subjected to significant prejudice and discrimination in the United States and other industrialized nations (Friedman & BrowneU, 1995; W a d d e n , W o m b l e , Stunkard, & Anderson, Chapter 8, this volume). It is hard to miss the cultural message that "thin is in." S o m e obese individuals, however, report that they are largely unaffected by their weight. They do not feel that it has adversely influenced their relationships with others, promotion at work, or overall enjoyment of life. Such individuals frequently note, "I'm pretty successful at everything I do except for this weight." In our experience, these individuals tend to have adult onset of their obesity, and thus were not teased or rejected (because of their weight) during childhood or adolescence (GrUo, Wilfley, Brownell, & Rodin, 1994; Sarwer & T h o m p s o n , Chapter 21, this volume). These individuals are also more likely to be m e n , given that obesity is generally associated with fewer social sanctions in males. O n the other end of the continuum are individuals w h o feel that their lives have been ruined by their weight (see section N of the W A L I ) . They recall, with great pain, h o w their parents scolded them for being fat, h o w their classmates teased and shunned them, h o w they never felt comfortable at the beach or pool, and h o w they finally gave up hoping for a boyfriend or girlfriend. Their failed weight loss efforts only add to their heavy emotional burden. In our experience, these individuals are typically from upper-middle-class to upperclass families that view obesity as a significant aesthetic, moral, and social shortcoming. Such individuals are more likely to experience severe body image dissatisfaction (Sarwer, W a d d e n , & Foster, 1998). Stunkard and Mendelson (1967) described this condition almost 40 years ago, noting that afflicted individuals believe their bodies are "ugly and despicable and that others view them with hostility and contempt" (p. 1299). Sarwer and Thompson describe, in Chapter 21 of this volume, the multifaceted nature of body image disparagement and methods of assessing it. These include the Multidimensional Body-Self Relations Questionnaire (Cash, 1994), as w e U as the Body Dysmorphic Disorder Examination—Self-Report (Rosen & Reiter, 1996). Practitioners also m a y wish to obtain a measure of general quality of life—a popular though loosely defined construct. Traditionally, it has referred to the physical limitations and burden of suffering associated with illness, although today it m a y also encompass satisfaction with life areas as diverse as one's job, religious belief, or m o d e of transportation. The most widely used instrument is the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which includes eight scales that measure aspects of life including mental health, energy level, and role and social functioning (Ware & Sherbourne, 1992). The SF-36 is easily scored and has excellent validity and reliability. Studies have shown that obese individuals are more likely to report physical complications, including back pain and decreased energy (Barofsky, Fontaine, & Cheskin, 1998; LePen, Levy, Loos, Banzet, & Basdevant, 1998).
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Mood Disorder • " D o e s the individual have a m o o d disorder or other psychiatric condition?" A p proximately 2 0 % of obese w o m e n w h o seek weight reduction report significant s y m p t o m s of depression, although fewer than 1 0 % are likely to m e e t the Diagnostic a n d Statistical M a n u a l of M e n t a l Disorders, fourth edition ( D S M - F V ; A m e r i c a n Psychiatric Association, 1 9 9 4 ) criteria for a major depressive episode ( W a d d e n , A n d e r s o n , et al., 2 0 0 0 ) (see Table 10.1). W e routinely assess m o o d with the BDI-II. Scores of 1 3 or under o n the BDI-II are generally not of clinical concern, unless the patient reports suicidal ideation (Beck et al., 1996). W i t h scores over 13, w e review s o m e of the individual items to assess m o r e fully the patient's affect, behavior, a n d cognition. Scores of 2 9 or over indicate severe depression that definitely requires professional attention. M o o d m a y also be assessed informally by asking patients to describe, for the past m o n t h , their m o o d , sleep, energy level, a n d satisfaction with w o r k , leisure activities, a n d personal relationships. (Items 0 3 - 0 5 of the W A L I assess depressed affect.)
T A B L E 10.1. Diagnostic Criteria for Major Depressive Episode A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Note: D o not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations. (1) depressed m o o d most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood. (2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others) (3) significant weight loss when not dieting or weight gain (e.g., a change of more than 5 % of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains. (4) insomnia or hypersomnia nearly every day (5) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) (6) fatigue or loss of energy nearly every day (7) feelings of worthlessness or excessive or inappropriate guilt (which m a y be delusional) nearly every day (not merely self-reproach or guilt about being sick) (8) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) (9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. The symptoms do not meet criteria for a Mixed Episode. . . . C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism). E. The symptoms are not better accounted for by Bereavement, i.e., aher the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. Note. From American Psychiatric Association (1994). Copyright 1994 by the American Psychiatric Association. Reprinted by permission.
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Persons suffering from major depression should be treated for theh mood disorder prior to undertaking weight loss. In this regard, they should be treated in the s a m e m a n n e r as persons of average weight w h o present with m a j o r depression. W e i g h t reduction w U l not ameliorate m a j o r depression, despite s o m e patients' protests to the contrary, a n d h could exacerbate h ( W a d d e n & Bartiett, 1992). Rather than m a j o r depression, practitioners m a y be m o r e likely to encounter dysthymic disorder in obese individuals. D y s t h y m i c disorder is a chronic low-grade depression, as defined in D S M - I V a n d described in Table 10.2. It is frequently accompanied by binge eating a n d reports of distress with w o r k or personal relationships (Stunkard, Chapter 6, this volume). These complications are not a contraindication to weight reduction; these individuals can lose weight a n d will experience improvements in m o o d (Gladis et al., 1998). It is unlikely, h o w e v e r , that weight reduction will result in lasting improvements in m o o d . These
T A B L E 10.2. Diagnostic Criteria for Dysthymic Disorder A. Depressed mood for most of the day, for more days than not, as indicated either by subjective account or observation by others, for at least 2 years. Note: In children and adolescents, can be irritable and duration must be at least 1 year. B. Presence, while depressed of two (or more) of the following: (1) poor appetite or overeating (2) insomnia or hypersomnia (3) low energy or fatigure (4) low self-esteem (5) poor concentration or difficulty making decisions (6) feelings of hopelessness C. During the 2-year period (1 year for children or adolescents) of the disturbance, the person has never been without the symptoms in Criteria A and B for more then 2 months at a time. D. No Major Depressive Episode . . . has been present during the first 2 years of the disturbance (1 year for children and adolescents); i.e., the disturbance is not better accounted for by chronic Major Depressive Disorder, or Major Depressive Disorder, In Partial Remission. Note: There may have been a previous Major Depressive Episode provided there wras a full remission (no significant signs or symptoms for 2 months) before development of the Dysthymic Disorder. In addition, after the initial 2 years (1 year in chUdren or adolescents) of Dysthymic Disorder, there may be superimposed episodes of Major Depressive Disorder, in which case both diagnoses may be given when the criteria are met for a Major Depressive Episode. E. There has never been a Manic Episode . . . , a Mixed Episode . . . , or a Hypomanic Episode . . . , and criteria have never been met for Cyclothymic Disorder. F. The disturbance does not occur exclusively during the course of a chronic Psychotic Disorder, such as Schizophrenia or Delusional Disorder. G. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothroidism). H. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Specify if: Early Onset: if onset is before age 21 years Late Onset: if onset is age 21 years or older Specify (for most recent 2 years of Dysthymic Disorder): With Atypical Features . . . Note. From American Psychiatric Association (1994). Copyright 1994 by the American Psychiatric Association. Reprinted by permission.
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individuals may benefit from long-term psychotherapy and/or pharmacotherapy (Stunkard, Chapter 6).
History of Substance Abuse/Dependence or Physical/Sexual Abuse • "Does the patient have a history of substance abuse/dependence or of physical/sexual abuse?" O u r obese female patients generally report a very low alcohol intake, and fewer than 1 0 % have a history of alcohol or other substance abuse or dependence (see items G 3 - G 4 ) . O u r obese male patients usually report a higher alcohol intake, which in some cases clearly contributes to their excess weight. Alcohol or other substance use problems are also u n c o m m o n in our male patients, but w h e n such a problem is present, it should be treated prior to weight reduction. The few data available suggest that alcohol abuse or dependence is a negative predictor of treatment outcome (Valley & Grace, 1987). The W A L I includes two items that inquire about a history of sexual or physical abuse (see items 0 6 - 0 7 ) . T w o studies found that a history of sexual abuse w a s more frequent a m o n g extremely obese w o m e n than in those of average weight (Brewerton, O'NeU, Dansky, & Kilpatrick, 1999; Felitti, 1993), although there have been contradictory findings on this topic (Sansone, Sansone, & Fine, 1995; Wiederman, Sansone, & Sansone, 1999). Felitti (1993) found that w o m e n with a history of sexual abuse were more likely to terminate weight reduction therapy prematurely. They reportedly felt anxious and vulnerable as a resuh of weight loss. W h e n patients respond "yes" to the sexual abuse items, w e usually state, " Y o u indicated that you have been sexually abused. Did you receive any counseling or other help?" With patients w h o have received treatment, w e ask the extent to which they feel that they have recovered from the abuse. Patients often report, "It's still difficult, but I'm doing the best I can." Those w h o report that they have never received counseling require greater attention. About half a dozen patients assessed by W a d d e n reported that they had never discussed their abuse with anyone. It had remained a secret for 15 or more years. All of them experienced great sadness, pain, and remorse as they described what had happened. M a n y expressed anger and resentment. W e always encourage these patients to obtain counseling. S o m e decline, stating that they do not think it will help, is too expensive, or m a y create problems if family members find out. W e acknowledge these concerns, but reiterate h o w helpful professional assistance can be. W e ask that the patients caU in a couple of days after they have had a chance to think things over. W e also encourage patients to call if they find that they remain upset as a result of their disclosure. Physical or sexual abuse is not a contraindication to weight reduction. W e have found that these patients usually lose weight satisfactorily, although practitioners should be alert to the possible adverse experiences described by Felitti (1993). The key concern with sexual abuse, as h is with depression or other psychiatric conditions, is to ensure that obese individuals receive the care they need. This is the same care that would be provided to people of average weight.
Desired Changes in Psychosocial Status • "Does the patient expect psychosocial improvements with weight reduction, and are these expectations realistic?" M a n y patients indicate that they seek only to improve theh health, mobility, or energy level. Others, however, clearly seek to improve theh social life, self-esteem, or body image by losing weight. If goals such as these can be articulated at the
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outset of treatment, patient and practitioner can evaluate whether they are realistic. essary, additional interventions can be planned to achieve these goals. Summarizing Social/Psychological Factors
The great majority of obese individuals in the general population have essentially no psychological functioning (Friedman & BrowneU, 1995; Wadden et al.. Chapter 8, this volume). The same is true of most of those w h o seek weight reduction at specialty chnics, although patients frequently report frustration and disappointment with their weight. Approximately 10%) of patients w h o seek treatment are likely to have a clinically significant mood disorder that requires treatment prior to weight reduction (Wadden, Anderson, et al., 2000). In talking with such a patient, the practitioner might explain, "You seem to be having a hard time now. Your mood is blue; you are having trouble sleeping and concentrating; activities that used to be pleasurable no longer are; and you feel like things aren't going to get better. These are symptoms of a mood disturbance." The practitioner should check the patient's response to this feedback and continue, "I know you want to lose weight, and you will be able to. But it will be much easier to lose weight, and to start enjoying life again, if wefirsthelp you feel better. There are effective treatments for mood that include talking with someone or taking medicine." Patients are often disappointed when informed that weight reduction should be delayed until they receive treatment for their mood or other disorder. They should be assured that they will be more successful with weight control, as well as with other aspects of daily life, after getting the care they need. Patients with BED, dysthymic disorder, or body image disturbance may also benefit from psychological or pharmacological intervention, although weight reduction is possible in the absence of adjunctive therapy.
TEMPORAL FACTORS
This section of the assessment is an extension of the social/psychological evaluation quires about the timing of the planned weight loss effort. It seeks to answer two principal questions. Timing of Weight Loss • "Why has the patient decided to lose weight now?" Although this question may be answered perfunctorily (e.g., "Because I a m overweight and want to look better"), the practitioner should remember that the patient probably has been obese for many months, if not years; in all likelihood, something has happened recently to motivate the individual to reduce. Overweight individuals seek weight loss for a variety of reasons. These include poor physical health, distress about their appearance, feelings that their eating is out of control, prodding by a partner or employer, or the desire to reclaim personal lives that have been submerged under the demands of raising a family. In some cases, patients have experienced disappointment, sadness, anger, or other feelings, which should be examined before weight loss is initiated. Discussion of these experiences will illuminate such patients' psychosocial goals for weight reduction, as discussed previously. Favorable Time for V/eight Loss • "Is this a favorable time to lose weight?" Successful weight reduction requires time, effort, and sustained concentration and motivation. Ideally, a patient should be relatively
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free of major life stressors. We have found that protracted stress in intimate or professional relationships, as w e U as Ufe crises (i.e., death of a parent, financial or legal problems, etc.), disrupt patients' weight reduction efforts (Wadden & Letizia, 1992). In one study, patients w h o discontinued treatment during the first 2 months of a multicenter trial endorsed more stressors at baseline (as measured by items P1-P4 of the W A L I ) than persons w h o remained in treatment. The distinguishing stressors were "relationship with significant other," "events related to parents," and "financial or legal difficulties" (Wadden & Letizia, 1992). Persons w h o report that they are experiencing high stress, as compared to their usual levels, should consider delaying weight reduction until the stressor has passed. For example, an accountant might wait until after tax season to lose weight, or a mother of three young children might wait until after her kitchen remodeling has been completed. T h e goal during the interlude is to maintain a stable body weight. If, however, patients with stressful lives insist that they can meet the demands of treatment, w e usually defer to their judgment. S o m e report that weight is the one thing they can control in a life that otherwise feels out of control. The patient's travel or vacation schedule should also be considered. Preferably, the individual should have a 2- to 3-month block in which to attend treatment regularly. If a behavioral intervention is to be used, the individual should be able to attend the clinic at least every other week and preferably on a weekly basis. Thus, for instance, a business w o m a n w h o is going to be in town for the next 2 weeks but away for the following 3 weeks should probably wait until her return to begin weight loss. It is critical that patients get off to a successful start, which is facilitated by continuity of care during the first few months. Initial success (with weight loss) is associated with long-term success (Jeffery, Wing, & Mayer, 1998; W a d d e n & Letizia, 1992). False starts are demorahzing to both patients and providers and are often the result of missed visits early in treatment.
Summarizng Temporal Factors Patients who seek weight reduction are usually "ready" for treatment, as reflected by their having taken the initiative to contact a health care provider. Thus it is not surprising, in this self-selected sample, that tests of weight loss readiness generally do not predict attrition or weight loss (Fontaine, Cheskin, & AUison, 1997). Nevertheless, a practitioner should determine that a patient has selected a propitious time to lose weight. In the minority of cases in which timing does not appear favorable, the practitioner might remark, " Y o u clearly are motivated to lose weight and have given this issue a lot of thought. A s w e look at the next month, however, it seems that you're going to be very busy. W h a t do you think about waiting until after your business trip to begin your program? Your goal until that time would be to remain weight-stable." Tests of weight loss readiness are likely to be of greater benefit to primary care physicians, most of w h o m have hundreds of overweight and obese patients in their practices. S o m e of these individuals are likely to be motivated to lose weight, but have stopped talking with theh primary care providers about weight control (Wadden, Anderson, et al., 2000). These individuals m a y be able to reduce successfully with some support and structure. The greater challenge is to motivate patients w h o appear to be uninterested in weight control, either because they have m a d e previous unsuccessful attempts or because they do not believe that obesity is a serious problem. W o m e n appear to faU more often into the first category, and m e n into the second. With those w h o feel frustrated with weight loss, the practitioner should acknowledge, "I k n o w h o w frustrated you are with your weight. You have worked so hard on h. There are some n e w approaches that could be of help. I would be pleased to discuss them if you would hke." With males w h o appear unconcerned about their weight, a different approach m a y be useful: " Y o u seem like a guy who's determined to
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be successful in life. Tell me why you're not more interested in your weight. It's a health success." This approach, which borrows from motivational interviewing, is designed to elicit patients' curiosity about their inconsistent or contradictory behavior (Smhh, Heckemeyer, Kratt, & Mason, 1997).
S U M M A R Y A N D IDENTIFICATION O F T R E A T M E N T G O A L S
We conclude the behavioral assessment by briefly summarizing what we have learned abo contributors to the patient's obesity, and about the individual's psychosocial status and the timing of the current weight loss effort. In reviewing biological factors, a practitioner might remark: "You have been overweight since you were 12 years old, and you noted that your mother had a weight problem all of her life, as did her mother. In addition, you have lost and regained weight on several occasions. These factors suggest that you have a biological (or genetic) tendency toward obesity—a tendency that probably makes weight control more difficult for you than for the next person. This does not mean that you cannot lose weight; you certainly can. You may not, however, be able to reach as low a weight as you would like. W e can discuss h o w much weight you can expect to lose and keep off." The practitioner should then summarize findings from the other "BEST" components, as described previously. Patients should be ecnouraged to ask questions or to comment.
Identifying Goals of Treatment
Patient and practitioner are likely to have discussed the patient's goals of treatmen throughout the interview. However, these should be clarified; patients often have implicit assumptions or goals that need to be articulated. The immediate goal of treatment would appear to be to help patients lose weight. As noted previously, however, obese individuals often seek weight loss as a means to another goal. In our clinic, their principal motivations are to improve their health and/or appearance (Foster, Wadden, Vogt, &c Brewer, 1997). M a n y hope that weight loss will improve self-esteem, body image, or a failing marriage. In such cases, we ask patients to rate (on a 1-10 scale) the likelihood that they will obtain the desired psychosocial outcomes if they lose weight. W e also ask h o w much weight they think they need to lose to achieve these outcomes, and whether weight loss on previous occasions yielded the benefits desired. W e tell patients that weight loss typically does not change personality or intimate relationships. It may improve body image, self-esteem, or mood, but these events are also influenced by factors other than weight (Foster, Wadden, & Vogt, 1997; Wadden, Steen, Wingate, & Foster, 1996). Thus, if changes in these areas are the principal ones desired, the patient should consider the benefits of cognitive-behavioral therapy, interpersonal psychotherapy, or other interventions. Body image, for example, improves with cognitivebehavioral therapy in the absence of weight loss (Rosen, Orosan, & Reiter, 1995; Sarwer & Thompson, Chapter 21, this volume). By contrast, weight loss more reliably improves health complications of obesity, including hypertension, hypercholesterolemia, and Type 2 diabetes (NHLBI, 1998; World Health Organization, 1998). Losses of 5%)-10%) of initial weight are sufficient to improve these disorders, although larger losses usually have a greater impact (Sjostrom, Lissner, & Sjostrom, 1998; Wing et al., 1987). Atkinson (1993) has provided criteria for assessing medical success. In addition to health changes, w e ask patients to think of lifestyle changes that they would like to achieve as a result of weight loss. These might include walking stairs more easily, having the energy to play with children or grandchildren, or being able to enjoy
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tennis or basketball again. We suggest that patients measure their success, in large part, by the extent to which they reach these lifestyle goals. Weight loss reliably improves energy level and subjective well-being (Rippe et al., 1998; W a d d e n et al., 1997). Weight Loss Goals The approach described above encourages patients to focus on non-weight-related outcomes in lieu of a particular goal weight. Nevertheless, it is important to discuss patients' weight loss goals; almost all patients have them, even if they do not m a k e them explicit. T w o recent studies found that obese w o m e n with a B M I of approximately 37-38 kg/m^ needed to lose approximately one-third of their initial body weight in order to reach their "goal" weights (Foster, W a d d e n , Vogt, & Brewer, 1997; W a d d e n , Berkowitz, Sarwer, PrusWisniewski, & Steinberg, 2001). In one study, patients reported that they would be disappointed with a loss of 1 7 % of initial weight (Foster, W a d d e n , Vogt, & Brewer, 1997). The problem for practitioners and patients is that most behavioral and pharmacological therapies produce an average loss of only 1 0 % of initial weight—less than one-third of what patients would like to lose. These findings highlight the importance of educating patients about realistic weight loss goals. Practitioners should underscore that weight losses of 1 0 % of initial weight are a treatment success; they are sufficient to improve both health and appearance concerns. This message must be repeated several times before treatment begins and then throughout the course of therapy, particularly w h e n weight loss slows and then stops (at about the fourth to sixth month) (Wadden et al., 2001). Patients m a y be discouraged by the practitioner's suggestion of a relatively modest weight loss. The practitioner should empathize with this disappointment and suggest that patients wait and see whether they achieve their health and other goals with a 1 0 % loss. Foster, W a d d e n , Vogt, and Brewer (1997) found that patients achieved most of their goals with a loss of approximately 1 0 % - 1 5 % ) of initial weight. Morever, W a d d e n and colleagues (2001) found that patients were moderately satisfied with an end-of-treatment loss of 1 0 % - 1 5 % of initial weight. A frequent question is this: "Can I lose 1 0 % n o w , keep it off for 6 months, and then lose another 1 0 % ? " W e reply, "That m a y be possible. Let's see h o w you are doing after you lose the first 10%)." In actuality, biphasic weight loss of this kind appears relatively uncomm o n , given current behavioral and pharmacological interventions (Wadden, Berkowitz, et al, 2000). However, some individuals can achieve and maintain losses of 2 0 % - 3 0 % of initial weight, as shown by the National Weight Control Registry (Klem, Wing, McGuire, Seagle, & HiU, 1997). W e do not want to want to deflate patients' hopes at the outset of treatment by stating, " N o , all you can lose is 1 0 % . "
SELECTING THE BEST TREATMENT Reviewing the Options Following discussion of the patient's goals of weight reduction, we review treatment options. This discussion is guided by an algorithm presented by W a d d e n and Osei in Chapter 11 of this volume, which recommends treatment based upon the patient's B M I , associated risk factors, and history of weight control efforts. As a general rule, more intensive therapy is recommended for individuals with higher B M I s and a greater risk of health complications. Thus w e discuss the option of bariatric surgery with persons whose B M I is 40 kg/m^ or over, w h o have lost and regained weight repeatedly, and w h o have adverse physical con-
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sequences of their obesity. A portion-controlled diet, followed by pharmacotherapy for weight maintenance, is recommended to people w h o are uncomfortable with bariatric surgery. At the other end of the continuum, patients with a B M I under 30 kg/m^ m a y be advised to participate in a behavioral weight loss program or to focus instead on increasing their physical activity, with the goal of preventing weight gain. Selection of treatment is discussed more fully by W a d d e n and Osei in Chapter 11.
Overview of Course of Treatment This section of the interview concludes by providing patients with an overview of the selected course of treatment. This includes discussing the duration and frequency of treatment visits during thefirst6 months; the assignments patients will be asked to complete (e.g., keeping food and activity logs); and the expected results of therapy, including weight loss and improvements in physical and psychological functioning. If a behavioral intervention has been selected, patients are informed that they will need to devote 30 minutes a day to their weight control regimen. Patients are encouraged to ask questions about the proposed course of treatment. At the conclusion w e ask, "Knowing what you do about the proposed treatment, h o w confident are you that you possess the skills needed to successfully complete the program? H o w confident are you that you will successfully lose weight?" Patients give a number from 1 to 10 in which 1 is "not at all confident" and 10 is "extremely confident." For numbers less than 8, w e inquire, " W h a t skills do you need to acquire to feel more confident?" In short, w e want to ensure that patients begin treatment with adequate weight loss self-efficacy, given that this is one of the few consistent predictors of weight loss (Clark, Abrams, Niaura, Eaton, & Rossi, 1991; Glynn & Ruderman, 1986).
C O N D U C T I N G THE B E H A V I O R A L A S S E S S M E N T
The behavioral assessment requires a practitioner to obtain a formidable amount of in mation in a brief period. In addition, the clinician must convey interest in the patient by giving the individual ample opportunity to raise questions and concerns. As noted previously, w e mail patients the BDI-II and W A L I prior to the behavioral assessment and have them bring the completed materials to the appointment. In as few as 2 minutes, prior to meeting a patient, w e can review the materials and determine the areas that need significant attention. W e have observed informally that patients' completion of questionnaires and punctual attendance at the initial interview are markers for adherence and attendance during treatment. Persons w h o do not complete the questionnaires satisfactorily often dislike and do not complete the diet diaries and other h o m e w o r k assignments. This potential problem should be addressed with patients during the behavioral assessment. S o m e patients c o m e to the behavioral assessment feeling anxious. They feel ashamed of theh inability to control their weight and worry that they will fail in treatment again. They also frequently wonder whether a practitioner will be sensitive to their problems and treat them respectfully, or instead will be critical of their apparent shortcomings. Thus the health care provider should be aware that patients use the initial interview to conduct their o w n assessment of the practitioner. W e try to ensure that patients leave the behavioral assessment having learned something n e w about the nature and causes of their weight problem. They should also leave with a clear understanding of the course of the proposed therapy, if weight reduction is to be undertaken, and what they will need to do to be successful.
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Finally, we hope that patients leave feeling that they have been treated with respect and understanding. It is hard to grasp, in only 60 minutes, the m a n y years of effort that most obese individuals have already devoted to weight control. So m a n y have experienced sadness and frustration each time they lost and regained weight, in full view of family, friends, and coworkers. F e w health problems are as public as obesity. Practitioners must look to the future, to renew their patients' hope with the promise of n e w treatments. But they must also look to the past with respect and admiration for the individuals' previous efforts.
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APPENDIX 10.1. WEIGHT AND LIFESTYLE INVENTORY (WALI) The W A L I is designed to obtain information about your weight and dieting histories, your eating and exercise habits, and your relationships with family and friends. Please complete the questionnaire carefully and make your best guess when unsure of the answer. Feel free to use the margins and bottom of pages when you need more space for your answers. Y o u will have an opportunity to review your answers with a member of our professional staff. Please allow 1.5 hours to complete this questionnaire. Your answers will help us better identify problem areas and plan your treatment accordingly. Please be assured the information you provide will be regarded as strictly confidential and will only be available to our treatment staff. Thank you for taking the time to complete this questionnaire. Section A: Identifying Information ^Name ''Date of Birth
^Social Security # ^Age
^Date
lbs ^Weight
ft ^Height
inches
^Address 'Phone: Day
/ ^'Occupation/* of yrs at job
^°Phone: Evening
'^Highest year of school completed (circle one): 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 High school College "Ethnicity (circle): Other:
American Indian
Asian
16
Master's
Doctorate
African American
Hispanic
White
'''How did you hear about our program? ^Newspaper Friend
Physician Employer
_Other professional _Other (please specify):.
W e b site
Section B: W e i g h t History . yrs old 1. At what age were you first overweight by 10 lbs or more?. H o w do you remember that you were overweight at this time? (e.g., pictures, clothes size, others telling you) 1. What has been your highest weight after age 21?
lbs at
^yrs old
3. What has been your lowest weight (not due to illness) after age 21, which you have maintained for at least 1 year? lbs at yrs old, maintained for yrs Was this weight reached after a weight loss effort? Yes No 4. Check the statement that best describes you: "During the past 6 months m y weight has ..." decreased more than 10 lbs or more. decreased 5 to 10 lbs. Note. The W A L I as a whole is adapted from Wadden and Foster (2001). Copyright 2001 by the authors. Adapted by permission. Section J of the W A L I comprises the Questionnaire on Eating and Weight Patterns—Revised (QEWP-R; Yanovski, 1993).
A S S E S S M E N T O F THE O B E S E ADULT
210
been relatively stable. increased by 5 to 10 lbs. increased by more than 10 lbs. or more. 5. What was your weight: 6 months ago? 1 year ago? 2 years ago?
Jbs _lbs lbs
6. For each time period shown below, please list your m a x i m u m weight. If you cannot remember what your m a x i m u m was, make your best guess and mark " G " (for guess) next to your answer. In addition, please note any events related to your gaining weight during this period. For ages 16 and beyond, please identify the figure that most resembles yours at that time. Record the number of the figure.
A. B. C. D. E. F. G. H. I. I.
Age 5-10 11-15 16-20 21-25 26-30 31-35 36^0 41-50 51-60 61-70
M a x i m u m Weight
Figure #
Events Related to Weight Gain
Section C: Family V^eight History 1. Please indicate the average height and weight of your biological mother and father during their middle-age years. Also, please select, from thefiguresprovided in Section B, the ones that are most similar to your parents' body shapes. If you do not know your biological parents' height and weights, please mark N A (not applicable) in the spaces.
Behavioral Assessment of the Obese Patient Height Weight Current Age Parent (ft + in) A. Mother B. Father
(lbs)
211
(or year of death)
Figure*
2. Please indicate the height and weight of the following members of your immediate family.
A. B. C. D. E. F. G.
Family Member Spouse/ Significant Other Oldest Brother 2nd Oldest Brother 3rd Oldest Brother Oldest Sister 2nd Oldest Sister 3rd Oldest Sister
Height (ft + in)
Weight (lbs)
Current Age (or year of death)
Figure*
Section D: W e i g h t , Pregnancy, a n d Menstrual Cycle (For W o m e n Only) 1. Do you have children? Yes No If yes, A. What was your weight at the start of your pregnancy? What was your weight at delivery? lbs What was your lowest weight after delivery? lbs
lbs
B. What was your weight at the start of your second pregnancy? What was your weight at delivery? lbs What was your lowest weight after delivery? lbs C. What was your weight at the start of your third pregnancy? What was your weight at delivery? lbs What was your lowest weight after delivery? lbs D. What was your weight at the start of your fourth pregnancy? What was your weight at delivery? lbs What was your lowest weight after delivery? lbs
lbs
lbs
lbs
Please turn to the last page if you need more space. 1. Do you experience a regular menstrual cycle? Yes No If yes, A. Describe your eating around the time of your menstruation (circle one): Eat much less Eat less N o change Eat more Eat much more B. D o you crave particular foods around the time of your menstruation? Yes No C. If yes, which foods do you crave?
Section E: W e i g h t Loss History 1. Please record each major weight loss (i.e., diet, exercise, moderation, etc.) that resulted in a weight loss of 10 pounds or more. Take time to think over your previous efforts, starting with the first
212
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one, whether in childhood or adulthood. You may have difficulty remembering this information at first, but most people can if they take their time. Start with your first weight loss effort and proceed in order until you reach your most recent one. Age at Time of Effort
Weight at Start of Effort
* lbs lost
Method Used to Lose Weight
A. B. C. D. E. F. G. H. I. JPlease turn to the last page if you need additional space.
.
1. Please pick a number to indicate below h o w accurate you think you were in remembering and recording your weight loss history. Pick any number from 1 to 10: 1 = "not at all accurate'* and 10 = "completely accurate." Your number is . 3. In the past year, h o w many times have you started a weight loss program on your o w n that lasted for more than 3 days? 4. In the past year, h o w many times have you started a weight loss program that lasted for 3 days or less? 5. Have you ever experienced any significant physical or emotional symptoms while attempting to lose weight or after losing weight? Yes No If yes, please describe your symptoms, h o w long they lasted, and the type of professional help sought, if any. Problem
Year
Duration (wks)
Type of Professional Help
Section F: W e i g h t Loss Goals 1. H o w much weight would you like to lose?
lbs
2. This would bring you down to a body weight of
lbs
3. W h e n did you last weigh this amount? 4. H o w long was this weight maintained? 5. W a s it achieved after a weight loss effort?
months Yes
No
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213
6. If you are successful in our program, in changing your eating and exercise habits, how much weight do you realistically expect to lose after: A. 1 month?
lbs B. 3 months?
lbs C. 6 months?
lbs D. 12 months?
lbs
Section G: Tobacco and Alcohol Use 1. D o you smoke cigarettes? Yes A. H o w many do you smoke a day? B. H o w many years have you smoked?
No
If yes,
2. Have you ever smoked cigarettes and stopped? Yes No A. W h e n did you stop smoking? B. H o w many cigarettes did you smoke? Iday C. Did you experience any weight gain after stopping smoking? many pounds? 3. During the past year: A. H o w many glasses of wine did you drink a week? B. H o w many bottles of beer did you drink a week? C. H o w many mixed drinks or liqueurs did you have a week?_
If yes,
Yes
No
If yes, h o w
4. Have you ever had a problem with alcohol consumption or the use of other drugs? Yes No If yes, please describe the problem and any help you received for it.
Section H: Eating Patterns I 1. Please indicate the degree to which you believe each of the following behaviors causes you to gain weight. In answering these questions, please use the 5-point scale below. Pick the one number that best describes h o w much the behavior contributes to your increased weight: 1 = Does not contribute at all 2 = Contributes a small amount 3 = Contributes a moderate amount 4 = Contributes a large amount 5 = Contributes the greatest amount A. B. C. D. E. F. G.
Eating too much food Overeating at breakfast Overeating at lunch Overeating at dinner Snacking between meals Snacking after dinner Eating because I feel physicaUy hungry
A S S E S S M E N T O F THE O B E S E ADULT
214 H. I. J. K. L. M. N. O. P. Q. R. S. T. U. V. W. X.
Eating because I crave certain foods Continuing to eat because I don't feel full after a meal Eating because I can't stop once I've begun Eating because of the good taste of foods Eating in response to the sight or smell of food Eating while cooking or preparing food Eating when anxious Eating when tired Eating when bored Eating when stressed Eating when angry Eating when depressed/upset Eating when socializing/celebrating Eating when happy Eating when alone Eating with family/friends Eating at business functions
Please indicate any other factors that contribute a moderate amount or more to your weight gain.
2. H o w many days a week do you eat the following meals? Write the number of days in the space and the usual time of each meal. A. Breakfast:. B. Lunch: C. Dinner:
_days a week _days a week days a week
Time:. Time:. Time:
Morning snack: _ Afternoon snack:. Evening snack:
_days a week _ days a week . days a week
3. W h o prepares meals at your home? 4. W h o does the food shopping? 5. Please list your five favorite foods:.
6. D o you have any food allergies? gic reactions.
_Yes
No
If yes, please specify the food and the aller-
7. Please specify the amount (in 8-oz cups) of the followingfluidsyou typically consume a day. Skim milk Lowfat milk Whole milk Seltzer water Fruit juice Water Tea _Diet soda _Coffee Sugared soda Beer Wine _Other _Hard liquor 8. During a typical week, h o w many meals do you eat at a fast-food restaurant (including drivethrough and convenience stores)? Breakfast: meals a week Lunch: meals a week Dinner: meals a week 9. During a typical week, how many meals do you eat at a traditional restaurant, coffee shop, cafeteria, or similar establishment? Breakfast: meals a week
Behavioral Assessment of the Obese Patient Lunch: _ Dinner:
215
. meals a week _ meals a week
10. H o w many times a week do you typically eat out with others (including family)?.
Section I: F o o d Intake Recall Please indicate the foods you consume on a typical weekday.
Meal
Time
Location
Food and Beverages Consumed
Amount
Breakfast
Morning snack
Lunch
Afternoon snack
Dinner
Evening snack
Please indicate the foods you consume on a typical weekend day.
Meal
Breakfast
Morning snack
Lunch
Afternoon snack
Dinner
Evening snack
Time
Location
Food and Beverages Consumed
Amount
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Section J: Eating Patterns II 1. During the past 6 months, did you often eat an unusually large amount of food within a 2-hour period (an amount that most people would agree is unusually large)? Circle one: Yes No 2. During the times when you ate an unusually large amount of food, did you often feel you could not stop eating or control what or h o w much you were eating? Circle one: Yes No If no, skip to question 11 in this section. D o not complete questions 3-10. 3. During the past 6 months, how often, on average, did you have times when you ate unusually large amounts of food and feeling that your eating was out of control? (There may have been some weeks when it was not present—just average those in.) A. Less than one day a week B. One day a week C. T w o or three days a week D. Four or five days a week E. Nearly every day 4. Did you usually have any of the following experiences during these occasions? Please complete each item. A. Eating much more rapidly than usual? B. Eating until you felt uncomfortably full? C. Eating large amounts of food when you didn't feel physically hungry? D. Eating alone because you were embarrassed by h o w much you were eating? E. Feeling disgusted with yourself, depressed, or feeling very guilty after overeating? F. Eating large amounts of food throughout the day with no planned mealtimes?
Yes Yes Yes Yes Yes
No No No No No
Yes
No
5. Think about a typical time when you ate this way (that is, large amounts of food and feeling tha your eating was out of control). What time of day did the episode start? Circle one: A. Morning (8 a.m. to 12 noon) B. Early afternoon (12 noon to 4 P.M.) C. Late afternoon (4 p.m. to 7 p.m.) D. Evening (7 p.m. to 10 p.m.) E. Night (After 10 p.m.) 6. Approximately how long did this episode of eating last, from the time you started to eat until when you stopped and did not eat again for at least 1 hours? hours
minutes
7. As best you can remember, please list everything you might have eaten or drunk during that episode. If you ate for more than 2 hours, describe the food eaten and liquids drunk that you ate the most. Be specific—include amounts and brand names (when possible). Estimate as best as you can estimate. For example: 7 ounces Ruffles potato chips; 1 cup Breyer's chocolate ice cream with 2 teaspoons of hot fudge; 2 8-ounce glasses of Coca-Cola; and IVi ham and cheese sandwiches with mustard.
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217
Food Amount Brand (if possible)
8. At the time this episode started, h o w long had it been since you had previously finished eating a meal or snack? hours
minutes
9. In general, during the past 6 months, h o w upset were you by overeating episodes in which you ate unusually large amounts of food? A. Not at all B. Slightiy C. Moderately D. Greatly E. Extremely 10. In general, during the past 6 months, how upset were you by feeling that you could not stop eating or could not control what or h o w you were eating? A. Not at all B. Slightly C. Moderately D. Greatly E. Extremely 11. In general, during the past 6 months, how important has your weight or shape been in how you feel about or evaluate yourself as a person—compared to other aspects of your life (i.e., h o w you do at work, as a parent, or h o w you get along with other people)? Weight and shape . . . A. B. C. D.
were not very important. played a part in h o w I felt about myself. were among the main things that affected h o w I felt about myself. were the most important things that affected h o w I felt about myselL
12. During the past 3 months, did you ever make yourself vomit in order to avoid gaining weight after binge eating? Circle one: Yes
No
If yes: H o w often, on average, was that? A. Less than once a week B. Once a week C. T w o or three times a week D. Four or five times a week E. M o r e than five times a week
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A S S E S S M E N T O F THE O B E S E ADULT
13. During the past 3 months, did you ever take more than twice the recommended dose of laxatives in order to avoid gaining weight after binge eating? Circle one: Yes
No
If yes: H o w often, on average, was that? A. B. C. D. E.
Less than once a week Once a week T w o or three times a week Four or five times a week More than five times a week
14. During the past 3 months, did you ever take more than twice the recommended dose of diuretics (water pills) in order to avoid gaining weight after binge eating? Circle one: Yes
No
If yes: H o w often, on average, was that? A. B. C. D. E.
Less than once a week Once a week T w o or three times a week Four or five times a week More than five times a week
15. During the past 3 months, did you ever fast (not eat anything at all for at least 24 hours) in ord to avoid gaining weight after binge eating? Circle one: Yes
No
If yes: H o w often, on average, was that? A. B. C. D. E.
Less than once a week Once a week T w o or more times a week Four or five times a week More than five times a week
16. During the past 3 months, did you ever exercise for more than 1 hour specifically in order to avoid gaining weight after eating? Circle one: Yes
No
If yes: H o w often, on average, was that? A. B. C. D. E.
Less than once a week Once a week T w o or three times a week Four or five times a week More than five times a week
17. During the past 3 months, did you ever take more than twice the recommended dosage of a diet pill in order to avoid gaining weight after binge eating? Circle one: Yes
No
If yes: H o w often, on average, was that? A. B. C. D. E.
Less than once a week Once a week T w o or three times a week Four or more times a week More thanfivetimes a week
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Section K: Eating Patterns III
In reference to the past 6 months, please circle ONE answer for each question, except where dir otherwise on questions 2, 3, and 11. 1. What level of appetite do you usually have in the morning? 0 None
1 Very low
2 Low
3 Moderate
4 High
2. When do you usually eat for the first time? (Mark an X on the line where appropriate.) I. 6 A.M.
9 A.M.
Noon
3 p.m.
I 6 p.m. or later
3. How much of your daily food intake do you consume after supper? (Mark an X on the line wher appropriate.) I
0%
I
25%
50%
75%
100%
4. How often do you have trouble getting to sleep? 0 Never
1 Sometimes
2 Half the time
3 Usually
4 Always
5. How often do you get up in the middle of the night? 0 Never
1 Once/month
2 Once/week
3 Once/night
4 More than once/night
6. When you get up in the middle of the night, how often to you snack? 0 Never
1 Sometimes
2 Half the time
3 Usually
4 Always
7A. To what extent do you have cravings or urges to eat snacks after supper, but before bedtim 0 None at all
1 A little
2 Somewhat
3 Very much so
4 Extremely so
B. To what extent do you have cravings or urges to eat snacks when you wake up at night? 0 None at all
1 A littie
2 Somewhat
3 Very much so
4 Extremely so
8. To what extent do you believe you need to eat in order to get back to sleep when you awake a night? 0 None at all
1 A little
2 Somewhat
3 Very much so
4 Extremely so
Check here if you did not get up
9.1f you snack in the middle of the night, how aware are you of your eating? 0 Unaware
1 Mostly unaware
2 PartiaUy aware
3 Mostly aware
4 Completely aware
Check here if you don't snack in the middle of the night
10. Are you feeling blue or down in the dumps? 0 None at all
1 A little
2 Somewhat
3 Very much so
4 Extremely
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A S S E S S M E N T O F THE O B E S E ADULT
11. When you are feeling blue, when is your mood better? 0 Early morning
1 Late morning
2 Afternoon
3 Early evening
4 Late evening/ nighttime
12. When you are feeling blue, when is your mood lower? 0 Early morning
1 Late morning
2 Afternoon
3 Early evening
4 Late evening/ nighttime
13. How long has your current episode of difficulty with night eating been going on? (Mark an X on the line where appropriate.) I Never
3 mo
6 mo
_1 1 yr
9 mo
Check here if more than 1 year
Section L: Physical Activity 1. To what extent do you enjoy physical activity? (Check one) Not at all Slightly Moderately Greatly 2. D o you have any physical problems that limit your physical activity? Yes
No
If yes, please describe:
3. Please check the types of physical activity you enjoy: Check only those that you have participated in during the last year. A. Walking outside D. Running
E. Biking outside
G. Aerobic class K. Golf
B. Walking (indoors, including treadmill) F. Biking (stationary)
H. Tennis/racket sports
L. Dancing
C. Jogging
I. Swimming
J. Basketball
M . Strength training
N. Other (please describe):
4. For your most preferred activity, how many times have you participated in this activity in the 6 months? times 5. How many hours of TV do you watch on an average weekday? hours 6. H o w many hours of T V do you watch on an average weekend day?
hours
7. Approximately how many city blocks or the equivalent do you regularly walk each day? blocks (12 blocks = 1 mile) 8. How many flights of stairs do you climb up each day? flights/day (let 1 flight = 10 steps) 9. Please describe your daily lifestyle activity (i.e., h o w active you are) by picking any number from 1 to 10 in which 1 = "very sedentary" and 10 = "very active." Your number:
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221
Section M : Family a n d Living A r r a n g e m e n t s 1. I a m currently (check one): Single Married Divorced Separated Widowed 2. Currently, I am (check all that apply): Living alone Living with a spouse/partner Living with significant other Living with children Living with parents/stepparents Living with other relatives Living with roommates 3. Please indicate the total number of persons living in your home:._ 4. If you are currently involved in an intimate relationship (significant other), please answer these questions. A. W h a t is this person's attitude toward your efforts to lose weight? (Check one) Strongly supports m y efforts Supports m y efforts Neutral Opposes m y efforts Strongly opposes m y efforts B. Please describe briefly what this person does to either help or hinder your efforts to lose weight.
5. H o w satisfied are you with your overall relationship with this person? (Check one) Very satisfied Satisfied Neutral Dissatisfied Very dissatisfied 6. Will other people support your efforts to lose weight ?
Yes
N o If yes, h o w m a n y will?.
W h o are these people? H o w m a n y of these people are actively helpful to you ? . 7. H o w m a n y people do you talk with about your weight w h e n you are upset about it?. H o w m a n y of these people are helpful to you? 8. Will other people oppose or undermine your efforts to lose weight? Yes
No
If yes, h o w m a n y will?
W h o are these people?
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A S S E S S M E N T O F THE O B E S E ADULT
Section N: Self-Perceptions 1. How satisfied are you with your current weight? (Check one) Very satisfied Moderately satisfied Slightly satisfied Neutral Slightly dissatisfied Moderately dissatisfied Very dissatisfied 2. How satisfied are you with your current shape (i.e., figure or physique)? (Check one) Very satisfied Moderately satisfied Slightly satisfied Neutral Slightly dissatisfied Moderately dissatisfied ^Very dissatisfied 3. How satisfied are you with your current overall appearance? (Check one) Very satisfied Moderately satisfied Slightly satisfied Neutral Slightly dissatisfied Moderately dissatisfied Very dissatisfied 4. Pick the one sentence that best describes your overall feelings about yourself: "In general, I am . . very happy with w h o I am. happy with w h o I am. O K with w h o I am, but have some mixed feelings. unhappy with w h o I am. very unhappy with w h o I am. 5. Pick the one sentence that best describes you: "As compared with most people, I think I have . . , very good self-esteem. good self-esteem. average self-esteem. poor self-esteem. very poor self-esteem. 6. Pick the one sentence that best describes your feelings about the w a y you looked the last time you lost a lot of weight: "I was ..." very happy with the w a y I looked. happy with the w a y I looked. O K with the w a y I looked, but with some mixed feelings. unhappy with the way I looked. very unhappy with the w a y I looked.
Behavioral Assessment of the Obese Patient 7. H o w much weight did you lose? lbs
223
lbs And at what weight did you start to diet during this time?
Section O : Psychological Factors 1. Have you ever had any problems at any time with depression, anxiety, or other emotions that disrupted your normal functioning? Yes
No
2. Have you ever sought professional help for emotional problems? If yes, please specify below. Problem
Year
Duration (wks)
Type of Professional Help
3. During the past month, have you felt depressed, sad, or blue much of the time? (Circle one) Yes
No
4. During the past month, have you often felt hopeless about the future? (Circle one) Yes
No
5. During the past month, have you had little interest or pleasure in doing things? (Circle one) Yes
No
6. Have you ever been subjected to physical abuse? 7. Have you ever been subjected to sexual abuse?
Yes Yes
No No
8. Are any of your immediate family members alcoholic?
Yes
No
Section P: Timing 1. Please indicate if you are currentiy experiencing any stress in your life related to the following events. Complete each item by checking the appropriate box. A.
Work:
B. C.
Health: Yes No Relationship with spouse/significant other:
D.
Activities related to your children:
E.
Activhies related to your parents:
Yes
F.
Legal/financial trouble:
No
G.
School:
H.
Moving:
Yes
Yes Yes
No
Yes
Yes
Yes
No
No No
No No
I. Other: Please explain in a sentence any items to which you responded yes:
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A S S E S S M E N T O F THE O B E S E ADULT
2. Are you planning any major life changes (e.g., new job, moving, relationship, etc.) during the ne 6 months? No Yes If yes, please briefly describe below:
3. H o w stressful has your life been during the past 6 months? Pick a number between 1 and 5, in which 1 = "much less stressful than usual," 2 = "less stressful than usual," 3 = "average level of stress,'' 4 = "more stressful than usual," and 5 = "much more stressful than usual." Your number is . 4. H o w stressful do you think that your life will be in the next 6 months, excluding your efforts to lose weight. Pick a number from 1 to 5, as in item 3 above. 5. H o w motivated are you to lose weight at this time? Pick a number between 1 and 10, in which 1 = "not motivated" and 10 = "greatest motivation you have ever had." Your number is . 6. Why do you want to lose weight right now, as compared to 1 year ago? What has prompted you to lose weight now?
7. What is the single most important thing that you hope to achieve as a result of losing weight?
8. People w h o want to achieve long-term weight control need to spend at least 30 minutes a day, for a minimum of 6 months, trying to change their eating, exercise, and thinking habits. Please check the sentence below that best describes you: I definitely will not be able to devote 30 minutes daily to weight control. I'm not sure if I can find 30 minutes daily for weight control. I can definitely find 30 minutes daily for weight control. I can devote more than 30 minutes daily to weight control. 9. Rate how confident you are that you will be able to significantly change your eating and exercise habits. Pick a number from 1 to 10 in which 1 = "not at all confident" and 10 = "extremely confident." Your number is . Please use this space to discuss any other information that you think is important to understanding you and/or your weight and your successful participation in the program.
Behavioral Assessment of the O b e s e Patient
225
Section Q : M e d i c a l History 1. Please indicate if you have had or have any of the medical conditions listed below:
Yes Heart disease Angina (chest pains) Palpitations, fast or hard heartbeats Stroke, mild stroke (cerebrovascular accident) Rheumatic fever Heart m u r m u r Pacemaker Breathing problems (asthma, lung disease) High blood pressure Anemia Back problems Joint or bone problems Hiatal hernia Arthritis Gout (elevated uric acid) Gallbladder disease Thyroid problems Kidney disease Ukers Bowel disease Liver disease Diabetes (Type 1 or 2) Sleep apnea Other (specify):
No
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A S S E S S M E N T O F THE O B E S E ADULT
2. List all medications being taken (including vitamins and supplements). Please indicate the dosage and frequency of each medication. Medication
Dosage
Frequency
Reason for Taking
Please indicate your primary care physician's name, telephone number, and address here. Name: Address:
Phone:
PART
T R E A T M E N T
O F
IV
A D U L T
O B E S I T Y
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1 1
T h e
Treatment A n
of
Obesity:
O v e r v i e w
T H O A A A S A. W A D D E N SUZE-^E OSEI
In 1998, an expert panel assembled by the National Heart, Lung, and Blood Institute (NHLBI, 1998) conducted an exhaustive review of the safety and efficacy of treatments for obesity. It issued recommendations for selecting a m o n g interventions, based on an individual's body mass index (BMI) and risk of health complications. The panel's lengthy report was distilled by a joint committee into the Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults ( N H L B I & North American Association for the Study of Obesity [ N A A S O ] , 2000). This briefer document provides primary care practitioners with additional guidelines and tools for treating overweight and obese individuals. Both of these documents are essential reading for persons interested in weight management. This chapter adheres to the recommendations of the joint N H L B I and N A A S O (2000) panel, and provides additional detail about various treatment options. T h e chapter seeks to help practitioners identify the most appropriate therapy for a given individual. A s such, it offers a framework for selecting from the dietary, behavioral, pharmacological, surgical, and other interventions described in the chapters that follow this one.
SELECTING T R E A T M E N T The decision to initiate weight loss should be based on an assessment of a patient's need to reduce, as described in this volume by Atkinson (Chapter 9) and Aronne (Chapter 18), and on the individual's behavioral readiness for weight loss, as discussed by W a d d e n and Phelan (Chapter 10). These factors, together with the B M I , suggest which interventions are likely to be most appropriate for a particular patient. 229
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TREATMENT O F ADULT OBESITY
Treatment Algorithms Aronne (Chapter 18, this volume) has reviewed the NHLBI and NAASO (2000) algorithm for selecting therapy (see Table 18.4 on page 396). Persons with a B M I of 25.0-29.9 kg/m^ w h o have two or more risk factors are encouraged to consume a balanced low-calorie diet, to increase their physical activity (so that they eventually exercise 30 minutes a day most days of the week), and to modify inappropriate eating habits. Alternatively, prevention of weight gain is recommended for persons in the same B M I range w h o are not motivated to reduce or w h o have fewer than two risk factors. As B M I increases, so generally do the health complications of obesity and the need for more intensive intervention. Pharmacotherapy is an option for persons with a B M I > 30 kg/m^ (or a B M I > 2 7 kg/m^ in the presence of comorbid conditions) and w h o have failed to reduce using more conservative measures. Bariatric surgery is reserved for individuals with a B M I > 4 0 kg/m^ or those with a B M I & 35 kg/m^ w h o have significant comorbid conditions. W a d d e n , BrowneU, and Foster (in press) have proposed a stepped-care algorithm that, similar to that developed by the N H L B I and N A A S O (2000) panel, recommends treatment based on the patient's B M I and risk of health complications (see Figure 11.1). The principal difference between the two schemes is the greater number of treatment options listed by the former algorithm and the stronger encouragement for persons with a B M I of 27-29 kg/m^ to lose weight. The presence of a single risk factor, such as hypertension or Type 2 diabetes, would appear to provide ample reason to undertake weight loss. Moreover, prevention of weight gain for individuals w h o fall into the B M I range of 27-29 kg/m^ is likely to require periodic bouts of caloric restriction, as well as increased physical activity, to reverse weight gain that occurs over the winter months or at other times. In overweight and obese adults, intentional weight loss, even w h e n followed by weight regain, does not appear to be associated with (1) increased risks of morbidity or mortahty, (2) adverse effects on metabolism or energy expenditure, or (3) the precipitation of eating disorders or depression (Foster, Sarwer, & W a d d e n , 1997; Gregg & W U U a m s o n , Chapter 7, this volume; National Task Force on the Prevention and Treatment of Obesity, 1994, 2000; W a d d e n , Foster, Stunkard, & Conill, 1996). Thus there do not appear to be strong reasons to dissuade persons with a B M I of 27-29 kg/m^ from attempting to lose weight.
Treatment Selection Treatment selection should be guided not only by the individual's BMI and heahh risks, but also by the patient's history of weight loss efforts. For example, w e have encountered many obese males (BMI > 30 kg/m^) w h o were eligible for pharmacotherapy but w h o had never participated in a traditional behavioral program of diet and physical activity. The latter intervention is less expensive than pharmacotherapy and is associated with fewer risks of health comphcations. Pharmacotherapy m a y be useful with these individuals for maintaining weight loss, but is not necessary to induce h. By contrast, h is hard to argue that a w o m a n with a B M I of 35 kg/m\ Type 2 diabetes, and a marked history of weight cycling should enroll in yet another diet and exercise program. She is more likely to achieve longterm success with long-term pharmacotherapy or with bariatric surgery. Diet and activity modification will remain an important focus of treatment, but they would need to be supported by these other interventions. Patients should have tried a less intensive treatment option once or twice before selecting a more aggressive therapy, but h is not necessary to try the less intensive option again with each n e w practitioner. Treatment options must also be selected with consideration of theh safety, efficacy, and cost. Self-help programs, for example, are very attractive because of their safety and low cost, but they usually produce minimal weight loss (Womble, W a n g , & W a d d e n , Chap-
Treatment of Obesity: An Overview Classification Decision Level 1 BMI < 27 kgltn
Stepped-Care Decision Step1 Self-directed diet and exercise Physician counseling
231 Matching Decision Suggested Treatment ^ Less Intensive Option •k More Intensive Option
Level 2 BMI 27-29 kg/m'
Step 2 Self-help program Commercial program Behavioral program
Less Intensive Option: No primary risk factor(s) Lower-body obesity Female, older
Level 3 BMI 30-39 kginf
Step 3 Portion-controlled, low-calorie diet (900-1200 kcal/day) Pharmacotherapy
More Intensive Option: Primary risk factor(s) Upper-body obesity Male, younger
Level 4 BMI>40kg/m^
Other Considerations: Previous efforts Patient preferences Emotional distress
F I G U R E 11.1. A conceptual scheme showing a three-stage process for selecting treatment. The first step, the Classification Decision, divides people into four levels based on body mass index (BMI). This level indicates which of four classes of interventions are likely to be most appropriate in the second stage, the Stepped-Care Decision. The interventions range from low-intensity, low-cost approaches, such as self-directed diet-and-exercise programs, to extremely aggressive and expensive interventions such as bariatric surgery. All individuals are encouraged to control their weight by increasing their physical activity and consuming an appropriate diet. W h e n this approach is not successful, more intensive intervention m a y be warranted, with the most conservative treatment (i.e., lowest cost and risks of side effects) tried next. The thick, solid arrows between the boxes shows the class of treatments that is usually most appropriate for an individual w h e n less intensive interventions have not been successful. The third stage, the Matching Decision, is used to m a k e a final treatment selection, based on the individual's prior weight loss efforts, treatment preferences, and need for weight reduction (as judged by the presence of comorbid conditions or other risk factors). The dashed arrows point to treatment options for persons with a reduced need for weight reduction because of a reduced risk of health complications. The thin arrows show the more intensive treatment options for persons w h o , despite relatively low B M I levels, have increased risks of health complications. Adjunct nutritional or psychological counseling is recommended for patients w h o report marked problems with meal planning, depression, body image, or like difficulties. F r o m W a d d e n , Brownell, and Foster (in press). Copyright by the American Psychological Association. Reprinted by permission.
ter 19, this volume). T h u s such p r o g r a m s m a y not be a g o o d choice for a n individual w h o needs to lose approximately 1 0 % of initial weight to improve a weight-related health c o m phcation. Individual preferences also m u s t be considered. Given that patients m u s t actively participate in their weight m a n a g e m e n t (i.e., by modifying eating and activity habits and/or by taking medications), they m u s t find the therapy acceptable. Concerns about the safety of s o m e approaches, including pharmacotherapy or surgery, m u s t be respected in view of the history of complications associated with these interventions. Similarly, patients m a y raise objections to specific diet or exercise regimens. A health care provider can suggest that a pa-
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TREATMENT O F ADULT O B E S I F
tient try a specific approach for a week or two, as an experiment, with the hope that it will prove acceptable. It is inappropriate, however, to push patients to accept a single diet or exercise plan w h e n there are so few data to inform patient-treatment matching (i.e., tailoring). Clearly, one size does notfitall. Kumanyika has discussed, in Chapter 2 0 of this volu m e , the importance of responding to individual differences and preferences in selecting an appropriate weight loss intervention.
TREATMENT OPTIONS: BMI < 30 kg/m2 Approximately 36% of aduh Americans have a BMI of 25.0-29.9 kg/m^, placing them in the "overweight" category as defined by the N H L B I (1998) and the World Health Organization (1998). Surveys indicate that most of these individuals, w h e n trying to lose weight, do so on theh o w n — b y dieting (i.e., restricting food intake), exercising, or both (Serdula, Collins, WiUiamson, P a m u k , & Byers, 1993). These persons also buy miUions of diet books and exercise videos each year, although little is k n o w n about the effectiveness of these interventions. Primary Care Physicians Aronne (Chapter 18, this volume) has described the role of primary care physicians in preventing and treating obesity. This includes monitoring patients' weight (and B M I ) on a regular basis, providing literature on healthy eating and activity habits, and assessing and managing weight-related heahh comphcations. S o m e physicians m a y wish to provide more intensive weight management, potentially by giving patients a structured treatment manual, having a registered dietitian consult in the office, or establishing an afternoon or evening clinic to provide brief check-in visits (i.e., to measure weight, collect food records, etc.). Primary care physicians often report that they feel ill prepared to treat overweight individuals, whether because of lack of adequate training, poor reimbursement, or a sense of futility—a feeling "that nothing works" (Aronne, Chapter 18; Frank, 1993). Patients may well sense their physicians' lack of involvement. Nearly three-quarters of participants in a recent study reported that they looked to their doctors only a "slight amount" or "not at aU" for advice about weight management (Wadden, Anderson, et al., 2000). Nearly 4 5 % indicated that their doctor had not prescribed any of 10 c o m m o n weight loss methods. These data suggest that physicians and their obese patients m a y have landed in a weight management stalemate: N o one talks about the problem. O n a more positive note, fewer than 1 0 % of patients reported that they were treated disrespectfully by their doctors concerning their weight. Moreover, most respondents were quite satisfied with the medical care they received for their general health. It is challenging for most primary care physicians to provide effective diet and exercise counseling in traditional office practice, because they are not equipped to meet with their patients on a weekly or biweekly basis—the frequency of care that is likely to produce the best results (at least in the short term). Nevertheless, physicians can play an important role in the management of overweight and obesity by providing an atmosphere in which patients can discuss their concerns and frustrations about their weight. Moreover, practitioners can provide a valuable service by familiarizing themselves with treatment options available in their community and using these resources (Aronne, Chapter 18). This includes identifying a registered dietitian with w h o m to establish a consultative relationship. (A local dietitian m a y be identified by caUing 800-366-1655.) Physicians can similarly support their patients' participation in self-help or commercial programs by inquir-
Treatment of Obesity: An Oven/iew
233
ing at office visits about satisfaction with these programs and congratulating patients on weight loss or behavior change.
Self-Help and Commercial Programs Self-tielp Programs Overweight individuals who are unable to reduce on their own, or with their physicians' advice, m a y benefit from the greater structure and support provided by self-help and commercial programs (reviewed in this volume by W o m b l e et al.. Chapter 19). Self-help programs charge no fee or only a nominal one (e.g., a dollar per week), and yet m a y induce weight losses as large as those produced by some of the most expensive proprietary programs. Latner and colleagues (2000), for example, recently reported that participants in a highly structured, group behavioral self-help program lost an average of 17.9 kg during the first 2 years and maintained a m e a n loss of 15.7 kg at 5 years. The 5-year findings were based on only the 2 1 . 6 % of participants w h o remained in the program at this time, but these are still impressive results, particularly in light of the negligible costs of the program. Take Off Pounds Sensibly (TOPS) and Overeaters A n o n y m o u s (OA) offer additional low- or no-cost alternatives that are available nationwide (see T O P S Club, 2000, and O A , 1996). F e w data, h o w ever, are available to evaluate the effectiveness of these latter two programs (Womble et al.. Chapter 19). Commercial Programs Outcome data have become increasingly important to commercial weight loss programs because providers can no longer m a k e claims of long-term success unless they have data to support them. N o t surprisingly, no commercial programs n o w advertise that their participants "lose weight and keep it off forever," as they did prior to the Federal Trade C o m m i s sion's (1997) action against several companies. Weight Watchers has taken the lead a m o n g commercial programs in evaluating its results of treatment. A recent study revealed that patients w h o were randomly assigned to attend a conventional Weight Watchers program lost 6.0% of initial weight in 6 months (Heshka et al., 2000). Persons assigned to a self-directed weight loss approach that included two meetings with a registered dietitian lost 2 . 5 % of initial weight. These results indicate that the Weight Watchers program, which combines group support with a sound program of diet, exercise, and behavior modification, can be of benefit to overweight and obese individuals at a reasonable cost (i.e., about $12 per week). Participants, on average, do not lose large amounts of weight, but losing as few as 2-3 kg after the holidays would appear to be better than continuously gaining weight. Moreover, even if participants do not lose a lot of weight, they do not lose a lot of money. In the absence of efficacy data from other commercial programs, it is hard not to select Weight Watchers as afirstintervention for overweight individuals w h o want more structure and cannot find a self-help program. Behavioral Weight Loss Programs Weight Watchers and other commercial programs have incorporated m a n y of the components of the behavioral treatment of obesity that was developed in university clinics in the late 1960s (Stuart, 1967). W i n g has described, in Chapter 14 of this volume, the theoretical underpinnings of the behavioral approach, as well as hs short- and long-term treatment results. Patients typically lose 8 % - 1 0 % of inhial weight during 4-6 months of weekly group treatment (Wing, 1998, and Chapter 14, this volume). Approximately 8 0 % - 8 5 % of participants complete treatment. Thus, traditional behavioral interventions are likely to produce
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T R E A T M E N T O F ADULT OBESITY
greater weight loss than are most commercial programs, although this hypothesis has not been tested in randomized trials. There are numerous accounts of the components of behavioral treatment, which include self-monitoring, stimulus control, problem solving, cognitive restructuring, social support, nutrition education, physical activity, and the use of reinforcement contingencies (Brownell, 2000; W a d d e n & Foster, 2000; W i n g , 1998). Brownell (2000) has provided a 16-week, step-by-step manual that covers these topics in a detailed but user-friendly manner. Rather than repeat this description, this section briefly discusses some of the mechanics of behavioral treatment that w e believe contribute to its successful induction of weight loss. This begins with the fact that behavioral treatment is very goal-oriented. Participants are given h o m e w o r k assignments (for changing eating, activity, and thinking habits), which are specified in terms that can be easily operationalized and measured. This is true whether the goal is walking after dinner five times a week for 2 0 minutes, keeping a daily record of food intake, decreasing the number of self-critical statements, or limiting breakfast to 275 kilocalories (kcal). Treatment sessions eschew lecturing by the group leader and instead are devoted principally to reviewing patients' completion of h o m e w o r k assignments and helping them find solutions to barriers. Frequent Visits Behavior change is facilitated by meeting with patients on a weekly basis. Frequent visits provide not only more opportunities for instruction, but also more opportunities for staff to review and reinforce patients' completion of food and activity records. Anticipation of weekly weigh-ins motivates most patients to adhere to the prescribed behaviors, and weight change provides a crude but critical measure of adherence. T h e failure to weigh participants each week is likely to result in suboptimal weight loss, as suggested by the results of a study by Goodrick, Poston, Kimball, Reeves, and Foreyt (1998). Time-Limited Therapy Most behavioral programs last 16-26 weeks. Treatment (at least during the weight loss induction phase) has a clear beginning and end, which appears to help patients pace themselves. They can set their sights on a specific date to complete treatment and achieve a sense of accomplishment, compared with the practice in open-ended therapy of having participants attend sessions indefinitely. Identifying a "treatment end date," however, is clearly a misnomer, given that patients require long-term behavioral or pharmacological treatment to maintain their weight loss. Even knowing this, patients usually prefer to divide maintenance therapy into time-limited blocks; this is similar to enrolling in a course for a semester, with the knowledge that additional courses will be needed. Group Treatment Behavioral treatment is typically delivered to groups of 10-20 persons. The use of closed treatment groups, in which the same patients begin and end treatment together, appears preferable to the use of open groups, in which n e w m e m b e r s m a y be added to the group at any point in treatment. The addition of n e w members after thefirstfew weeks impairs the development of group cohesiveness and m a y contribute to the high attrhion rates that characterize commercial programs that use open groups (Volkmar, Stunkard, Woolston, & Bailey, 1981). Moreover, h is difficuh to estabhsh a curriculum of behavior change, in which one week's session builds upon another, if patients in the same group are at different stages of treatment.
Treatment of Obesity: An Overview
235
Group treatment is not only more cost-effective than individual therapy but also may produce larger weight losses. A recent study found that persons w h o requested individual therapy but were randomly assigned to group treatment nevertheless achieved significantly greater weight losses than participants w h o requested individual therapy and received it (RenjUian et al., 2001). The benefits of group treatment may derive not only from the support that patients provide each other, but also from a heahhy dose of competition. Patients may push themselves to keep up with the group norm.
Treatment Flexibility
Although behavioral treatment as described here is highly structured, the treatment p can be used to help patients adopt a variety of different eating and activity plans. Traditional behavioral interventions, for example, encourage patients to consume a balanced-deficit diet of approximately 1,200-1,800 kcal/day, as described by Melanson and Dwyer in Chapter 12 of this volume. Behavioral principles, however, can be used to facilitate adherence to diets that vary dramatically in their macronutrient or calorie content, including very-low-calorie diets (VLCDs) or plans that allow ad libitum intake of carbohydrate with only small amounts of fat. The same behavioral principles can be used to increase programmed exercise, lifestyle activity, or both, as described by Wing (Chapter 14, this volume). Thus "behavioral treatment" refers to the principles and techniques that are used to change eating and activity habits, rather than to the specific diet or exercise plan that is to be adopted.
Limitation of Behavioral Treatment Traditional group behavioral treatment is appropriate for overweight or obese individuals who have failed to reduce on their o w n or w h o have not been successful with self-help or commercial programs. The greater intensity and structure provided by this approach should be of benefit. The greatest drawback of group behavioral treatment is its limited availability. Health care providers (in the United States) are encouraged to contact their local hospital, university psychology chnic, sports medicine clinic, or Y M C A to determine whether they offer a closed-group behavioral program as described above. A local registered dietitian may also offer such treatment. In the absence of referral sources, practitioners may wish to use The L E A R N Program for Weight Management 2000 (Brownell, 2000). (The manual may be ordered at 800-736-7323.)
TREATMENT OPTIONS: BMI OF 30-39 kg/m2
One-quarter of U.S. adults have a BMI > 30 kg/m^, which places them in the "obese" cat gory. The algorithm in Figure 11.1 lists two options for persons with a B M I of 30-39 kg/m^ who have failed to reduce using the less intensive (and less expensive) options described previously. The options are (1) a low-calorie, portion-controlled diet; and (2) pharmacotherapy.
Low-Calorie, Portion-Controlled Diet The N H L B I (1998) recommended that persons with a B M I of 27-35 kg/m^ w h o wish to lose weight reduce their intake by 300-500 kcal/day, with the goal of losing 1 0 % of initial weight in 6 months. Persons with a B M I over 35 kg/m^ are encouraged to reduce their intake by 500-1,000 kcal/day in order to achieve a comparable reduction in the same time. Caloric intake is restricted more severely with heavier individuals because they have to lose more weight (in absolute terms) to achieve a 1 0 % reduction.
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TREATMENT O F ADULT OBESITY
Although reducing daily caloric intake by a certain amount (e.g., 500-1,000 kcal/day) m a y sound easy, it frequently is not because people do not k n o w their baseUne energy requirements (to maintain weight). In addition, equations for estimating calorie requirements often miss the mark by 2 0 % or more w h e n applied to a given individual (Foster et al., 1988). This shortcoming has led some practitioners to simplify matters by prescribing a diet of 1,000-1,500 kcal/day for obese w o m e n and 1,500-1,800 kcal/day for m e n (Brownell, 2000; Wing, 1998). (Heavier individuals are usually instructed to aim for the higher end of the calorie range.) FoUowing this approach, w o m e n are prescribed what the N H L B I (1998) has defined as a "low-calorie diet" (LCD): a diet providing 800-1,500 kcal/day. The diet of 1,500-1,800 kcal/day prescribed for m e n is sometimes referred to as a "balanced-defich diet" ( B D D ) , as discussed by Melanson and D w y e r (Chapter 12, this volume) in this voL ume. (This term actually refers to the balanced, or even, reduction in the macronutrient composition of the diet. The energy content of B D D s often ranges from 1,000 to 2,000 kcal/day.)
Structured /V\eal Plans and Liquid /Aeal Replacements Wing has reviewed, in Chapter 14 of this volume, the use of structured meal plans and liquid meal replacements, which induce larger weight losses than those produced by a self-selected diet of conventional foods with the same targeted calorie goal. Ditschuneit, Flechtner-Mors, Johnson, and Adler (1999), for example, found that patients w h o met with a dietitian once a month and were prescribed a diet of 1,200-1,500 kcal/day that included two servings a day of a liquid meal replacement (i.e., SlimFast) lost 7.1 kg in 3 months, compared to a loss of 1.3 kg for participants w h o were instructed to consume a self-selected diet of the same caloric value. Portion-controlled servings, by providing foods of a predetermined quantity and calorie content, reduce obese individuals' tendency to underestimate their calorie intake—an underestimation that is as great as 5 0 % w h e n a self-selected diet of conventional foods is consumed (Bandini, Schoeller, Cyr, & Dietz, 1990; Prentice, Black, Coward, & Cole, 1996). By coming closer to their prescribed calorie goal, patients are more likely to achieve their desired weight loss. This is particularly important with individuals with a B M I > 30 kg/m-^ w h o often feel that they have so m u c h weight to lose. Portion-controlled foods m a y be useful not only for inducing larger initial weight losses, but also for facilitating the maintenance of weight loss (Flechtner-Mors, Ditschuneit, Johnson, Suchard, & Adler, 2000). Very-Low-Calorie Diets The use of liquid meal replacements evolved in part from the popularity in the 1980s of V L C D s , defined by the N H L B I (1998) as diets providing fewer than 800 kcal/day. V L C D s provide large amounts of protein (i.e., 70-100 g/day) to prevent the loss of lean body mass, and m a y be consumed as a hquid formula or as lean meat,fish,and fowl (referred to as a protein-sparing modified fast). Both diets appear to be safe w h e n supplemented with adequate vitamins and minerals, and w h e n provided to appropriately selected patients under careful medical supervision, as described previously (National Task Force, 1993; Wadden &C Berkowitz, 2001). V L C D s , however, are associated with an increased risk of gallstones— a complication that can be prevented by taking ursodeoxycholic acid (Broomfield et al, 1988). V L C D s produce reductions of approximately 1 5 % - 2 5 % of initial weight in 8-16 weeks of treatment—losses approximately double the size of those produced in the same time by a B D D of 1,000-1,600 kcal/day composed of self-selected conventional foods (Anderson, Vichitbandra, Qian, & Kryscio, 1999; National Task Force, 1993; W a d d e n &C
Treatment of Obesity: An Overviev\/
237
Bartiett, 1992). At least seven randomized trials have compared the short- and long-term results of these two dietary approaches (Miura, Aral, Tsukahara, O h n o , & Ikeda, 1989; Ryttig, Flaten, & Rossner, 1997; Togerson, Lissner, Lindroos, Kruijer, & Sjostrom, 1997; Wadden, Foster, &c Letizia, 1994; W a d d e n , Sternberg, Letizia, Stunkard, & Foster, 1989; Wing, Blah, Marcus, Epstein, & Harvey, 1994; W i n g et al., 1991). Table 11.1 summarizes four of these studies and shows that patients treated by both approaches regained weight in the year following treatment. Those treated by a V L C D , however, regained substantially more weight, so that at follow-up (12 or more months after patents achieved their maxim u m weight loss) there were not statistically significant differences between the V L C D and the B D D . Only one study to date found a substantial advantage at follow-up for the V L C D (Miura et al., 1989). These findings raise questions concerning whether V L C D s are worth the greater expense (i.e., approximately $3,000 for a 6-month program), compared with a traditional B D D providing 1,000-1,500 kcal/day. Moreover, three studies compared liquid diets providing 420 kcal/day versus 800 kcal/day and found they produced equivalent weight losses, raising additional questions about the need for severe caloric restriction (i.e., <800 kcal/day) (Foster et al., 1992; Kanders, Blackburn, Lavin, & Norton; O h n o , Miura, Aral, Tsukahara, & Ikeda, 1989). For these reasons, our research team has discontinued use of V L C D s in favor of a diet providing 900-1,000 kcal/day. This diet combines four servings of a nutritional supplement (OPTIFAST 800) with an evening meal that consists of a frozen food entree and a fruit and vegetable serving (Wadden et al., 1997). This regimen produced a loss of 1 7 % of initial weight in 16 weeks, w a s well tolerated by patients, and required only minimal medical monitoring because of the higher calorie level. Patients were examined by a physician (and a biochemical profile w a s obtained) at baseline and at weeks 8 and 24. Thus a portioncontrolled L C D can be provided at a substantially lower cost than a V L C D because of the reduced need for physician monitoring and laboratory tests. Patients are likely to obtain optimal results with a portion-controlled L C D by participating in a structured behavioral program, as described previously. In addition, prior to treatment, patient and practitioner must devise a program to facilitate the maintenance of weight loss, given that patients appear just as likely to regain weight following a portioncontrolled L C D as they are following a V L C D (Wadden et al., 1997). A s noted previously, long-term use of a liquid meal replacement m a y help to facilitate the maintenance of weight loss (Flechtner-Mors et al., 2000).
Pharmacological Treatment of Obesity Weight loss medications are another option for persons with a B M I > 30 kg/m^, or a B M I ^ 27 kg/m^ in the presence of obesity-related risk factors or comorbid conditions ( N H L B I &C N A A S O , 2000; National Task Force, 1996). In our opinion, pharmacotherapy's greatest strength, particularly compared with traditional behavioral treatment, would appear to reside in facilitating the maintenance rather than the induction of weight loss. Sibutramine and orlistat, the two medications currently approved by the U.S. Food and Drug Administration for long-term use, have been shown to produce losses as great as 8 % - 1 0 % of initial weight 2 years postbaseline, as long as patients remained on medication (Davidson et al., 1999; James et al., 2000; Sjostrom et al., 1998). Long-term behavioral treatment, as reviewed by Perri and Corsica in Chapter 17 of this volume, appears to be equally effective; however, it is likely to require more time and effort (of both patient and provider), and it is rarely provided outside of research and hospital clinics. Thus pharmacotherapy has the potential to m a k e effective treatment available to far greater numbers of persons, although this hypothesis remains to be tested.
T A B L E 11.1
Reference Ryttig, Flaten, & Rossner (1997)
ro CJ 00
Togerson et al. (1997)
Comparison of Very-Low-Calorie Diets (VLCDs) versus Balanced-Deficit Dkts (BDDs) providing 1,000-1,6000 kcal/day
Subjects 44 F, 37 M (42)
74 F, 39 M (87)
Mean pretreatment weight (kg) 114.2
110.9 126.15
Wadden, Foster, &: Letizie (1994)
49 F (37)
106.3
Wing etal. (1994)
93 F (74)
106.75
Maximum mean weight loss (kg)
Mean weight loss at follow-up (kg)
112 112
W k 8: 7.2" W k 8: 9.2''
112 wk:5.5 112 wk:5.9
112
W k 8: 9.2*
112 wk:5.7
104
W k 26: 15.9"
104 wk:9.2
104
W k 26: 8.6*
104 wk: 6.2
39.3 1. BDD (1,200 kcal/day) + BT. ; 2. B D D for 1 wk; V L C D (420 kcal/day) for wk. 2-17; B D D (1,000-1,200 kcal/day) for w k 18-52.
52 52
W k 26: 11.9" W k 26: 21.5*
78 wk: 12.2 : 78 wk: 10.9
51.8 1 BDD (1,000-1,200 kcal/day)+BT for lyr. 2. V L C D (400-500 kcal/day) for w k 1-12 and 24-36 + BT.
50 50
W k 26: 14.5 W k 26: 16.8
104 w k:5.7 104 w k:7.2
Mean age (yr) 42.5
Treatment regimen
Mean treatment duration (wk)
1. B D D (1,600 kcal/day) for 112 wk. 2. V L C D (420 kcal/day) for 8 wk, followed by B D D (1,600 kcal/day) for 104 wk. 3. V L C D for 8 wk, followed by B D D using nutrient packets for 104 wk.
47.1 1. VLCD (456 kcal/day for women, 608 for men) + B T for 12 wk, foUowed by B D D (1,200-1,800 kcaPday) + B T for 92 wk. 2. BT + B D D for 104 wk.
Note. F, female; M , male; number in parentheses = subjects remaining at longest follow-up; BT, behavior therapy. Values of maximum mean weight loss with different superscripts (a vs. b) are significantly different from each other.
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In this volume, Bray (Chapter 15) has reviewed current and potential agents for the treatment of obesity, and Aronne (Chapter 18) has discussed the prescription of weight loss agents by primary care physicians. Several other thoughtful reviews of this topic are available (Atkinson & Hubbard, 1994; Bray, 1993; Bray & Greenway, 1999; National Task Force, 1996). Thus the present discussion is hmited to four related issues: (1) the size of the weight losses to be expected with medication, (2) the relation between behavioral and pharmacological interventions, (3) methods to facilitate medication adherence, and (4) the longterm use of pharmacotherapy.
Size of Weight Losses Sibutramine and orlistat induce mean reductions of approximately 7%-10% of initial weight during the first 6 months of treatment—a loss nearly identical to that produced by traditional behavioral treatment. Weight loss usually stops (i.e., plateaus) at this time, despite patients' remaining on medication (for up to 2 years). As m a n y as 4 0 % of participants treated by either medications m a y lose 1 0 % or more of initial weight, but even the most successful individuals fall far short of the 2 5 % reduction in initial weight that patients expect to achieve (Wadden, Berkowitz, Sarwer, Prus-Wisniewski, & Steinberg, 2001). Efforts to increase weight losses by combining sibutramine and orlistat (which have different and potentially complementary mechanisms of action) were not successful in a pilot study of this approach, but further studies are needed (Wadden, Berkowitz, et al., 2000). Combining weight loss medications with a strong behavioral program m a y yield larger weight loss.
Relation of Behavioral and Pharmacological Treatment Currently approved pharmacological agents induce weight loss by modifying internal signals that regulate hunger and/or satiety (as with sibutramine) or by causing nutrient malabsorption (as with orlistat) (Wadden et al., 2001). Medications in the first group m a y reduce the desire to initiate (or to continue) eating. Behavior modification, by contrast, induces weight loss by helping patients modify the external environment (Craighead & Agras, 1991). For example, patients are instructed to select smaUer portion sizes, to avoid convenience stores and fast-food restaurants, to store foods out of sight, and to avoid engaging in other activities while eating. The desire to eat is controlled by limiting exposure to events that precipitate eating. Thus pharmacotherapy and behavior therapy would appear to induce weight loss by different but potentially complementary mechanisms. Combining these two approaches could be expected to induce larger weight losses than either intervention used alone. This belief is supported by the results of a study by Craighead, Stunkard, and O'Brien (1981). Patients w h o were treated weekly for 26 weeks by group behavior modification alone (i.e., without medication) lost an average of 10.9 kg (about 1 1 % of initial weight). Those treated by pharmacotherapy alone (120 mg/day of fenfluramine), in brief monthly office visits, lost a significantly smaller 6.0 kg (about 7 % ) . The combination of medication plus weekly group behavior modification resulted in a m e a n weight loss of 15.3 kg (about 1 6 % ) . Thus medication and behavior therapy appeared to have additive effects. The withdrawal from the market of fenfluramine and dexfenfluramine, because of their association with valvular heart disease, obviously limhs the clinical significance of these findings (Connolly et al., 1997). A recent study, however, of sibutramine and behavior modification (the latter therapy is n o w often referred to as "lifestyle modification") yielded similar findings (Wadden et al., 2001). A total of 53 obese w o m e n were randomly assigned to one of three conditions, all of which received 1 year of treatment. Those in the
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first group (i.e., drug-alone condition) were prescribed 15 mg/day of sibutramine and were instructed to consume 1,200 kcal/day and to exercise four to five times a week for 30 minutes per bt)ut. Patients had 10 brief physician visits during the year to check their blood pressure and any side effects; however, they received no formal instruction in modifying their eating or activity habits. Patients in a second group (i.e., drug plus lifestyle) also received 15 mg/day of sibutramine and the same diet and exercise prescription. These participants, however, also attended weekly group sessions during thefirst5 months at which they were instructed in behavioral methods of weight control, including keeping daily records of their food intake and physical activity. Sessions were led by psychologists, w h o followed The L E A R N Program for Weight Control (Brownell & W a d d e n , 1998). Participants attended monthly meetings from months 5 to 12. Participants in the third group (i.e., combined treatment) received the same program, except during the first 4 months, they consumed 1,000 kcal/day of a portion-controlled diet. This consisted of four servings/day of a liquid diet ( O P T I F A S T 800), combined with an evening meal of a frozen food entree and a vegetable and a fruit serving. This diet w a s included to induce a larger initial weight loss, given previous findings that obese w o m e n were disappointed by modest weight losses (Foster, W a d d e n , Vogt, & Brewer, 1997). Figure 11.2 shows that the addition of group lifestyle modification to sibutramine increased weight loss almost threefold. Patients w h o received the drug alone lost 4 . 1 % of initial weight at the end of the year, compared with a loss of 1 0 . 8 % for those w h o received the drug plus lifestyle modification. W o m e n w h o received the drug plus the portion-controlled diet (i.e., combined treatment) lost 1 6 . 5 % of initial weight—an outcome similar to that re-
F I G U R E 11.2. Percentage reduction in initial weight for w o m e n treated by sibutramine alone (i.e., drug alone) (n = 19), sibutramine plus group lifestyle modification (i.e., drug plus lifestyk) (n = 17), or sibutramme plus group lifestyle modification combined witii a portion-controUed diet providmg 1,000 kcal/day (i.e., combined treatment) (n = 17). From Wadden, Berkowitz, Sarwer, PrusWismewski, and Stemberg (2001). Copyright 2001 by the American Medkal Association. Reprinted by permission.
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ported in a sibutramine trial that included a 1-month VLCD (Apfelbaum et al., 1999). These results s h o w that although sibutramine alone (as typically prescribed in primary care practice) wUl induce weight loss, substantially better results are likely to be achieved by combining the medication with a patient's o w n efforts to modify eating and activity habits. Weight loss medications m a y facilitate the consumption of a healthier diet, but should not be considered a substitute for the patient's o w n efforts in this regard. A key challenge is to find effective ways of providing lifestyle modification during primary care visits (Wadden et al., 1997). Physicians w h o do not beheve that they have the time or expertise to provide such counseling m a y wish to prescribe medication but refer patients to a dietitian or selfhelp program to obtain the lifestyle modification. Combining pharmacotherapy with a group program of lifestyle modification required more time and effort of patients. However, the greater weight loss significantly improved patients' satisfaction with their treatment outcomes, including satisfaction with changes in their health and fitness, self-esteem, and body image. Satisfaction with all outcomes, including that with the medication, w a s positively related to patients' meeting their weight loss expectations. Prior to treatment, the w o m e n reported the number of pounds they expected to lose after 1, 3, 6, and 12 months of treatment. Patients, on average, expected at 1 year to lose the equivalent of 2 5 % of their initial weight—a loss that eluded even patients w h o received combined treatment. However, the greater the percentage of their expected weight loss patients achieved, the greater their satisfaction with changes in their weight, health and fitness, body image, and related outcomes. (Correlations ranged from r = .62 to .72.)
Facilitating /dedication Adherence In addition to improving patients' eating and exercise habits, behavioral principles m a y be used to facilitate adherence to weight loss medications. This is an important issue, given findings, for example, that as m a n y as half of persons prescribed antihypertensive agents do not achieve optimal control of blood pressure because of inadequate medication adherence (Dunbar & Stunkard, 1979). W h e n prescribing weight loss agents, practitioners m a y wish to review several issues with patients. These include: 1. Explaining the mechanisms by which the weight loss medication works. This includes describing what the medication will do (i.e., increase satiety or block fat absorption), as w e U as what the patient should do (i.e., decrease exposure to food triggers, record food intake, etc.). 2. Describing the medication's possible side effects and h o w the patient should respond to them. This includes having the patient call the practitioner before he or she stops taking the medication. 3. Inquiring whether the patient or the patient's family members have any health concerns about the use of medications (particularly in view of the adverse effects of the fenfluramines) or about costs of medications (which are not covered by most insurance plans). 4. Describing the course of treatment (at least for the first year), outlining medication use and the frequency of office visits, and discussing behavioral goals of treatment. 5. Developing a medication schedule that identifies w h e n and where patients will take their medication and what they should do in the event of missed doses. T h e more concrete the schedule, the better patients' adherence. 6. Having patients keep a daily medication log, at least during thefirstfew months. This log should be reviewed at subsequent office visits. 7. Reviewing h o w m u c h weight patients can realistically expect to lose during the first
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6 m o n t h s of treatment, and helping them define success in terms of non-weight-related outcomes. These might include improvements in health complications, increased fitness and mobility, or the ability to enjoy recreational or social activities that the individual has forgone because of excess weight ( W a d d e n et al., 2001).
Long-Term /V\edication Use Practitioners wiU also need to prepare patients for the slowdown in weight loss that typically occurs between the fourth and sixth months, after which most individuals stop losing weight altogether, despite remaining on medication. As shown in Figure 11.3, obese women treated by Wadden and colleagues (2001) expected to continue to lose weight from months 6 to 12. They were totally unprepared for the weight loss plateau that occurred at month 6, which is illustrated in Figure 11.2. Practitioners should inform patients that the weight loss plateau is to be expected (although it is not easily explained), and that medications work after the first 6 months to maintain the weight loss that has been achieved. This last point is critical, because most patients interpret the lack of continued weight loss as a sign that the medication is no longer working, and this leads them to discontinue therapy. Discontinuing medication usually results in rapid regaining of lost weight, which paradoxically illustrates how well the medication was working to maintain weight loss. This finding was observed in a recent study, in which 24 patients w h o had completed 68 weeks of treatment with sibutramine were encouraged by their physician to remain on the medication indefinitely to facilitate weight maintenance (Womble, Wadden, Berkowitz, Sarwer, & Rothman, in press). As shown in Figure 11.4, the five w o m e n w h o remained on medication
-M .c "55
0 <;
? -
:l 10 c
I :
i i
I
.E 15 •I 20 u "g 25 i_ O) 30 I § 35 I0) °- 40
1 mos
3 mos
6 mos
12 mos
Ultimate Loss
F I G U R E 11.3. Patients' expected reduction in initial weight aher 1, 3, 6, and 12 months of treatment Prior to treatment, partkipants reported the cumulative number of pounds they expected to lose by each period. These values were converted to percentage reduction in initial weight. "Ultimate loss" reflects the weight loss patients hoped ultimately to achieve, even if not during the 12-month study. From Wadden, Berkowitz, Sarwer, Prus-Wisniewski, and Steinberg (2001). Copyright 2001 by the American Medical Association. Reprinted by permission.
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at the 104-week assessment maintained their full end-of-treatment weight loss, whereas those w h o discontinued medication at w e e k 68 or shortly thereafter regained about 6 kg from w e e k 68 to w e e k 104. In order to be used o n a long-term basis, weight loss medications must be both safe and effective. Orlistat and sibutramine both appear to be effective, as judged by 2-year placebocontrolled trials (Davidson et al., 1999; James et al., 2 0 0 0 ; Sjostrom et al, 1998). Both also appear to be generally safe, although sibutramine is associated in s o m e patients with significant increases in blood pressure and pulse, and thus must be m o n h o r e d closely (Hansen, Tourbo, Stock, M a c d o n a l d , & Astrup, 1999; W a d d e n et al., 2001). Studies are n o w needed to determine the best schedule for maintaining patients on medication over the long term in order to maintain their weight losses over the long term. For example, it m a y be possible to limit medication use to every other m o n t h , as s h o w n with phentermine ( M u n r o , M a c C u i s h , Wilson, &c D u n c a n , 1968) or to prescribe medication primarily during high-risk periods for weight gain, such as during the winter holidays. Regardless of whether w e consider current medications or those yet to be discovered, they will have to be used on a long-term basis in the same fashion as agents for other chronic disorders, including hypertension, hyperlipidemia, and diabetes.
Early Drag Discontinuation Later Drag Discontinuation
Drag Continuation
Sibutramine Alone
Sibutramine + Orlistat/Placebo
Follow-Up
Weeks FIGURE 11.4. Change in body weight over 2 years in patients who discontinued sibutramine at week 68 (i.e., early drug discontinuation) (n = 13), w h o discontinued medication between weeks 68 and 104 (i.e., later drug discontinuation) (n = 6), and w h o continued medication until week 104 (i.e., drug continuation) (n = 6). During weeks 0-52, all participants received sibutramine. During weeks 52-68, all patients received sibutramine, while half were randomly assigned to orlistat and half to placebo. At the study's conclusion (week 68), all patients were encouraged to continue taking sibutramine to facilitate the maintenance of weight loss. Data from W o m b l e , Wadden, Berkowitz, Sarwer, and Rothman (in press).
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TREATMENT OPTIONS: BMI > 40 kg/m2 Persons with a BMI > 40 kg/m^ deserve special attention from health care providers. This is because extremely obese individuals typically experience more serious health complications, as well as more adverse psychosocial consequences, than do persons with lesser degrees of excess weight. The physical and psychosocial comphcations of extreme obesity are discussed in this volume by Field, Barnoya, and Colditz (Chapter 1), Latifi, Kellum, D e M a n a , and Sugerman (Chapter 16), and W a d d e n , W o m b l e , Stunkard, and Anderson (Chapter 8). Practitioners must ensure that these individuals receive the medical care that they need, independent of their need for weight reduction. Latifi and colleagues (Chapter 16) have described surgical interventions for the management of obesity, including vertical banded gastroplasty, gastric bypass, and gastric banding procedures. The gastric bypass would appear to be the treatment of choice for extremely obese individuals, given that the procedure induces an average loss of 2 5 % - 3 0 % of initial weight and is associated with excellent long-term weight loss and improvements in comorbid conditions (Albrecht & Pories, 1999; Latifi et al.. Chapter 16). Patients, however, must be fully informed of the risks of the procedures, which include an operative mortality rate of approximately 0.5%-1.0%. In addition, surgical candidates must understand that the gastric bypass will radically change their eating, in terms of reducing the amounts and types of foods that they can consume (particularly sweets and meats). At our program at the University of Pennsylvania, all candidates are screened not only by a surgeon and specialist in internal medicine, but also by a behavioral psychologist and dietitian. T h e latter two staff members describe the eating and activity habits that must be adopted after surgery; they assess the patients' readiness to m a k e these changes (Wadden, Sarwer, et al., 2001). O u r opinion of bariatric surgery has changed dramatically over the past 20 years, from thinking that it bordered on the barbaric to n o w beheving that the approach is underutUized. Bariatric surgery should be considered with all individuals w h o have serious obesity-related health complications and a B M I > 35 kg/m^ (or a B M I > 40 kg/m^ in the absence of major health complications). Candidates should have tried to lose weight using the safer, more traditional options of diet, exercise, and weight loss medication. Those, however, with a marked history of weight cycling (i.e., lost and regained a total of 50 kg or more) should consider bariatric surgery before embarking on another weight loss effort with traditional therapy.
IMPROVING THE MAINTENANCE O F WEIGHT LOSS Bariatric surgery receives high marks because it is associated with excellent maintenance of weight loss for up to 15 years after surgery (Albrecht & Pories, 1999; Latifi et al.. Chapter 16, this volume). By contrast, weight regain remains the Achilles's heel of both behavioral and pharmacological interventions. Remarkably little is k n o w n about the specific physiological and behavioral factors that contribute to weight regain, despite the reliabUity with which this occurrence is observed. By contrast, factors associated with the maintenance of weight loss are w e U k n o w n and include high levels of physical activity; consumption of a low-calorie, low-fat diet; regular monitoring of weight and food intake; and the use of positive coping strategies in response to lapses in diet and exercise adherence (Jeffery, Wing, Thorson, & Burton, 1998; Klem, Wing, M c G u h e , Seagle, & Hill, 1997; W a d d e n , 1995). In this volume, Perri and Corsica (Chapter 17), as well as W i n g (Chapter 14), discuss methods of facilitating patients' long-term adherence to these critical behaviors. Cooper and Fahburn (Chapter 22) propose a cognitive model that attributes weight regain in part to patients' negative body image. Obese individuals w h o are dissatisfied with theh weight
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and shape are unable to accept the modest 10% weight loss that behavioral and pharmacological therapies typically produce. Their frustration and disappointment ultimately lead them to abandon efforts needed to maintain the modest weight losses they have achieved. Several of the therapeutic interventions proposed by Cooper and Fairburn (Chapter 22) are used in nondieting approaches to weight management, as discussed by Foster and M c G u c k i n (Chapter 24).
LOOKING A H E A D This chapter has been written with the knowledge that the interventions described are likely to benefit the individuals w h o receive them but are inadequate to solve our nation's growing epidemic of obesity. This is because weight reduction therapy is currently available only to a minority of obese individuals, typically those w h o can pay out of pocket. Even with these persons, earnest efforts to modify eating and activity habits usually are n o match in the long term for a toxic environment that explicitly encourages the consumption of large portions of high-fat, high-sugar foods and implicitly discourages physical activity, as a result of fundamental changes in the nation's w o r k and leisure habits. Clearly, efforts are needed to improve the treatment of obesity, as well as to obtain recognition and reimbursement of this disorder. But far greater attention n o w must be devoted to the prevention of obesity, as described in this volume by Horgen and Brownell (Chapter 5) and Schmitz and Jeffery (Chapter 27), and to the treatment of childhood obesity, as discussed by Goldfield, Raynor, and Epstein (Chapter 26). Such efforts must attack the environment that lies at the heart of this disorder. This will require investigators and practitioners to w o r k not only in the laboratory and consulting r o o m but also in schools, workplaces, and other community settings. Those interested in the treatment of obesity must realize that the objects of their care are not only the individuals w h o present to them for treatment, but also the larger social and economic forces that shape our nation's eating and activity habits.
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Volkmar, F. R., Stunkard, A. J., Woolston, J., Sc Bailey, B. A. (1981). High attrition rates in commer cial weight reduction programs. Archives of Internal Medicine, 141, 426—428. Wadden, T. A. (1995). Characteristics of successful weight loss maintainers. In F. X. Pi-Sunyer & D. B. Allison (Eds.), Obesity treatment: Establishing goals, improving outcomes, and reviewing the research agenda (pp. 111-118). N e w York: Plenum Press. Wadden, T. A., Anderson, D. A., Foster, G. D., Bennett, A., Steinberg, C , & Sarwer, D. B. (2000). Obese women's perceptions of their doctors' weight management attitudes and behaviors. Archives of Family Medicine, 9, 854-860. Wadden, T. A., & Bartiett, S. J. (1992). Very low calorie diets: A n overview and appraisal. In T. A. Wadden Si T. B. VanltaUie (Eds.), Treatment of the seriously obese patient (pp. 44-79). N e w York: Guilford Press. Wadden, T. A., & Berkowitz, R. I. (2001). Very low calork diets. In C. G. Fahburn Si K. D. Brownell (Eds.), Eating disorders and obesity (2nd ed., pp. 529-533). N e w York: GuUford Press. Wadden, T. A., Berkowitz, R. I., Sarwer, D. B., Prus-Wisniewski, R., & Steinberg, C. (2001). Benefits of lifestyle modification in the pharmacologic treatment of obesity. Archives of Internal Medicine, 161,118-117. Wadden, T. A., Berkowitz, R. I., Vogt, R. A., Steen, S. N., Stunkard, A. J., Si Foster, G. D. (1997). Lifestyle modification in the pharmacologic treatment of obesity: A pilot investigation of a potential primary care approach. Obesity Research, 5, 118-116. Wadden, T. A., Berkowitz, R. I., W o m b k , L. G , Sarwer, D. B., Arnold, M., & Steinberg, C. (2000). Effects of sibutramine plus orlistat in obese w o m e n following one year of treatment by sibutramine alone: A placebo-controlled trial. Obesity Research, 8, 431—437. Wadden, T. A., BrowneU, K. D., Sc Foster, G. D. (in press). Obesity: Responding to the global epidemic. Journal of Consulting and Clinical Psychology. Wadden, T. A., Si Foster, G. D. (2000). Behavior therapy for obesity. Medical Clinics of North America, 84, 4 4 1 ^ 6 1 . Wadden, T. A., Foster, G. D., Si Letizia, K. A. (1994). One-year behavioral treatment of obesity: Comparison of moderate and severe caloric restriction and the effects of weight maintenance therapy. Journal of Consulting and Clinical Psychology, 62, 165-171. Wadden, T. A., Foster, G. D., Stunkard, A. J., &; ConUl, A. (1996). Effects of weight cycling on resting metabolic rate and body composition of obese women. International Journal of Eating Disorders, 19, 5-12. Wadden, T. A., Sarwer, D. B., & Berkowitz, R. I. (1999). Behavioral treatment of the overweight patient. Balliere's Clinical Endocrinology and Metabolism, 13, 93-107. Wadden, T. A., Sarwer, D. B., W o m b k , L. G , Foster, G. D., McGuckin, B. G , & Schimmel, A. (2001). Psychological aspects of obesity and obesity surgery. Surgical Clinics of North America, 81, 1001-1024. Wadden, T. A., Sternberg, J. A., Letizia, K. A., Stunkard, A. J., Sc Foster, G. D. (1989). Treatment of obesity by very low calorie diet, behavior therapy, and their combination: Afive-yearperspective. International Journal of Obesity, 13, 39-46. Wing, R. R. (1998). Behavioral approaches to the treatment of obesity. In G. A. Bray, C. Bouchard, & W . P. T. James (Eds.), Handbook of obesity (pp. 855-873). N e w York: Marcel Dekker. Wing, R. R., Blair, E., Marcus, M., Epstein, L. H., 8c Harvey, J. (1994). Year-long weight loss treatment for obese patients with Type II diabetes: Does including an intermittent very-low-calorie diet improve outcome? American Journal of Medicine, 97, 354-362. Wing, R. R., Marcus, M . D., Salata, R., Epstein, L. H., Miaskkwicz, S., Sc Blah, E. H. (1991). Effects of a very-low-calorie diet on long-term glycemic control in obese Type 2 diabetic subjects. Archives of Internal Medicine, 151, 1334-1340. W o m b k , L. G , Wadden, T. A., Berkowitz, S., Sarwer, D. B., & Rothman, R. A. (in press). Continued use of medication facilitates weight maintenance [Letter to the editor]. Obesity Research. Worid Health Organization. (1998). Obesity: Preventing and managing the global epidemic (PubHcation N o . W H O / N U T / N C D / 9 8 . 1 ) Geneva: Author.
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Popular Diets for Treatment of O v e r w e i g h t
a n d
Obesity
KATHLEEN M E L A N S O N J O H A N N A DWYER
Millions of individuals in industrialized societies are constantly attempting to lose excess weight, either o n their o w n , under their physicians' care, or through other programs (Galuska, WiU, Serdula, & Ford, 1999). However, most faU in the process, often growing more discouraged and even more obese as a result (National Heart, Lung, and Blood Institute [NHLBI], 1998; Pasman, Saris, & Westerterp-Plantenga, 1999). T h e myriad claims of advocates of different weight loss approaches lead m a n y dieters to choose inappropriate options (Galuska et al., 1999). In an effort to clarify this confusion, this chapter focuses on popular diets used to treat overweight and obesity. It begins by examining criteria for evaluating weight loss and maintenance strategies, and applying these to some popular diets. Diet foods and products, as well as special ingredients and techniques for achieving weight control, are discussed. Readers desiring a review of the physiological basis of weight loss, as well as the regulation of macronutrient intake, are directed to Appendix 12.1.
CRITERIA F O R E V A L U A T I N G V\^EIGHT L O S S S T R A T E G I E S During the hypocaloric phase of weight control efforts, there are seven criteria that the eating plan must meet. These are called the "seven C's," and are summarized in Table 12.1. The last three C's also apply to maintenance of a healthier weight, once it has been achieved.
Calories The size of the caloric deficit, and thus the amount of weight that will be lost, depend on the difference between the individual's usual food intake and the calorie level of the reducing diet. The energy needs of a person in energy balance can be estimated by using a formula 249
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TABLE 12.1. Seven Essential Criteria of Healthful Weight Control Plans 1. Calories 6. Components of sound weight management: 2. Composition • Healthful hypocaloric diet 3. Costs • Physical activity and exercise 4. Consumer friendliness • Behavioral modification 5. Coping with coexisting health risks • Psychological and social support and conditions 7. Continuation of provisions for long-term maintenance: • Decreased food intake compared to that prior to dieting • Increased physical activity and exercise
for resting metabolic rate ( R M R ) and multiplying the result by an "activity factor," based on the individual's level of physical activity. Several approaches to these calculations have been published, but a particularly straightforward one is presented here. The estimate of the energy needs of the body at rest, or R M R , can be calculated with the following formulas: Male: RMR = 900 + (10 x weight in kilograms) Female: RMR = 700 + (7 x weight in kUograms) Next, a multiplier is applied to the product to adjust for energy needs due to physical activity. The multipliers are 1.2 for individuals w h o are very sedentary, 1.5 for moderately active persons, and 1.8 for very active individuals. T h e result is a good starting point for estimating energy intake prior to weight loss. F r o m this estimate, a weight control regimen can be designed. For example, a 77-kg m a n would have an estimated R M R of 1,670 kilocalories (kcal)/day (900 + [10 x 77]), and if he is moderately active, he would have an estimated energy expenditure (and thus energy requirement for balance) of 2,505 kcal/day (1,670 x 1.5). M o s t American m e n eat about 2,800 kcal/day, and w o m e n about 1,800 kcal/day; however, actual intakes vary considerably by size, sex, body composition, activity level, and whether the person is in energy balance or gaining weight at the time the weight loss regimen is imposed. A pound of adiposetissueprovides about 3,500 kcal of available energy. Regardless of the intake level, an energy deficit of about 500 kcal/day, relative to daily energy consumption while in energy balance, will result in a loss of about 1 pound of body fat per week. A defich of 1,000 kcal/day wUl produce a loss of about 2 pounds per week. Weight losses of greater than 0.5-1 pound per week (0.23 to 0.45 kg) are not recommended unless the patient is medically supervised, and even under medical supervision, losses of more than 2 pounds/week of fat are not recommended. Weight losses more rapid than this increase the risk of excessive loss of lean body mass, as well as nutrient deficiencies, fatigue, and other side effects. The information above can also be used to calculate the size of the caloric defich and the likely weight loss for an individual w h o embarks on afixed-caloriediet plan, as prescribed by m a n y of the popular diet books. First, an estimate of the person's current energy intake is m a d e , using the formulas and activity factors just described above. The calories provided by the eating plan in the weight loss regimen can then be subtracted from the estimated current intake; the difference is the caloric deficit per day. Multiply it by 7 days per week and divide h by 3,500 kcal (the energy in a pound of body fat). T h e resuh is a rough approximation of the pounds lost per week if adherence is perfect. Such calculations are useful because they explain w h y two people m a y lose weight at very different rates on the same hypocaloric diet. For example, a moderately active m a n
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weighing 176 pounds would have energy needs of approximately 2,380 kcal per day. On a fixed reducing diet of 1,500 kcal, the caloric defich would be 880 kcal/day, and he would be expected to lose about 1.75 pounds a week. If his wife, a slightly active w o m a n w h o weighed 154 pounds and had an energy need of 1,666 kcal/day, consumed the same diet, she would have an energy deficit of only 166 kcal/day. She would lose less than 0.5 pound per week on the same diet. T h e point is that even with perfect adherence, whenever reducing diets or eating plans involve fixed caloric levels, people with different energy needs will lose different amounts of weight. For this reason, tailoring of weight reduction regimens is useful. Also, the metabolic effects of different caloric deficits are variable, and, of course, adherence is never perfect.
Composition The composition of the reducing diet may influence the composition of the weight lost, and it also affects overall nutritional status. Both total fasting and very-low-calorie diets (VLCDs) cause excessive breakdown of lean tissue, and consequent losses of water and nitrogen (VanltaUie & Yang, 1977).
Carbohydrate Carbohydrate needs are at least 50 g/day, even on VLCDs that are ketogenic. At least 100 g of carbohydrate, preferably 5 5 % or more of calories, should be provided for diets over 800 kcal/day. Diets providing fewer than 100 g/day of carbohydrates cause ketosis and m a y lead to excessive protein breakdown to maintain blood glucose levels. In general, w h e n the body must rely on degradation of protein's carbon skeletons to preserve blood glucose levels (via gluconeogenesis), the catabolism of the protein is accompanied by loss of water. For every gram of protein (or glycogen) that is broken d o w n , 3 g of water are released, causing rapid weight loss but also a state of relative dehydration (VanltaUie, 1980). This is not only undesirable from the standpoint of health; it also does not address the true purpose of a weightreducing strategy, which is to decrease excess adipose tissue. Dietary fiber, which is chemically similar to carbohydrate in most of its forms but is virtually noncaloric, should also be included in the reducing diet to facilitate normal laxation. O n a V L C D it is important to include at least somefiber,and on diets providing over 800 kcal/day, 20-30 g of fiber from various food sources are recommended. Inclusion of five or more servings of fruits and vegetables per day, with plenty of whole-grain breads and cereals, can help to meet this goal of obtaining both soluble and insoluble fiber. Intakes of complex carbohydrates and fiber should remain high during the maintenance period after weight loss has ceased. Patients should be reminded that as dietaryfiberintake increases, water requirements also increase. This is essential for maintaining softness of intestinal contents and thus normal taxation.
Protein Protein requirements are also critical on reducing diets. In hypocaloric states, protein needs are increased, especially on total fasts and V L C D s . W h e n energy intakes are insufficient, some amino acids are used to maintain blood glucose levels and others must be used for energy, so overall protein requirements increase (Calloway, 1975; Committee on Dietary Allowances, 1989). Fortunately, the hormonal milieu in hypocaloric states spares nitrogen and causes preferential use of fat for energy. Inevhably, however, along with loss of adipose tissue, some lean tissue (and also nitrogen) is lost. Losses of water, calcium.
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phosphorus, potassium, and vitamins follow the loss of lean tissue. Loss of more than 4 0 % of the initial lean body mass in a normal heahhy individual is life-threatening (Roubenoff & Kehayias, 1991). Lesser losses of lean body mass can also be hazardous, affecting cardiovascular function, exercise tolerance, and possibly i m m u n e responses, and thus should be avoided. A s a rule of thumb, a m i n i m u m of 65-70 g of protein is needed daily. O n a V L C D , 1.5 g of high-quality protein per kilogram of ideal body weight per day is desirable, with intakes no less than about 65-70 g. Intakes m a y need to be even higher if the dieter suffers from certain diseases or is physically stressed, since nitrogen losses m a y rise further in these states. O n 800-1,200 kcal/day, daily protein intake should be at least 1 g/kg ideal body weight. Reducing diets over 1,200 kcal/day should provide protein at a rate of at least 0.8 g/kg ideal body weight. Levels should remain this high after weight loss has stopped and maintenance has begun.
Electrolytes and Water Electrolyte levels are important, especially in fasting and on V L C D s ; cardiac arrhythmias have resulted from hypokalemia on such regimens (Amatruda, Biddle, Patton, & Lockw o o d , 1982). Since hypocalemia can be fatal, electrolyte levels must always be monitored. Hydration is also important, both to slake thirst and to avoid dehydration, particularly in hot climates or with physical exertion. M u c h of the very rapid weight loss that occurs in the first few days of dieting is due to diuresis and dehydration, particularly w h e n ketogenic, very-low-carbohydrate, low-calorie diets (LCDs) are employed. A s mentioned earlier, losses of body glycogen and protein are accompanied by losses of body water. Thus intake of lowor no-calorie fluids such as water should be emphasized. Beverages containing caffeine and alcohol should not be encouraged, since they increase diuresis. W h e n the individual engages in very vigorous physical activity, electrolytes and water should be monitored. Often the fatigue that some dieters associate with hypocaloric diets is actually due, at least in part, to dehydration. Body water losses of as little as 2 % have been associated with decreased physical and mental performance, as w e U as with impaired thermoregulation (Kleiner, 1999). The daily recommendation of at least 8 glasses of water is especially important for dieters; they often require even more. Thus a fluid intake plan should be incorporated in every weight loss regimen.
Vitamins and /V\inerals Vitamins and minerals are also critical on reducing diets. T h e recommended dietary allowance for an individual's age and sex must be met in both usual and reducing diets. The lower the diet is in calories, the more likely h is that other essential nutrients and electrolytes (such as potassium, magnesium, vitamin Bg, iron, and calcium) wUl be low. As a rule of thumb, diets below 1,200 kcal/day are likely to require vitamin and mineral supplements. Above 1,200 kcal/day, iron and calcium supplements m a y still be needed by w o m e n in the reproductive age groups, but most other nutrient needs can be met by a well-balanced diet that follows the Dietary Guidelines for Americans (U.S. Department of Agriculture [ U S D A ] & U.S. Department of Health and H u m a n Services [ U S D H H S ] , 2000). For this reason, foods with high micronutrient density but low energy density are especially important on a reducing diet. The guidelines for the composition of weight-reducing diets, as discussed above, are outlined in Table 12.2.
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TABLE 12.2. Guidelines for Composition of Healthy Weight Control Plans Carbohydrate V L C D : > 5 0 g/day L C D : >100 g/day Protein V L C D : 1.5 g/kg body wt. (>65-70 g/day) L C D : 1.0 g/kg body wt. B D D : 0.8 g/kg body wt. Fat s 3 0 % of dietary energy from total fat £ 1 0 % of dietary energy from saturated fat Fiber 20-30 g/day Water 8 glasses (~2 quarts or 2 liters) More needed with exercise and/or heat Vitamins/minerals Supplemented on V L C D and L C D (to recommended daily allowance) Iron and calcium for w o m e n of reproductive age Alcohol Minimal to none Note. VLCD, very-low-calorie diet (<800 kcal/day); LCD, low-calorie diet (800-1,200 kcal/day); BDD, balanced-deficit diet (>1,200 kcal/day).
Cost The cost of weight loss programs is probably one of the reasons w h y so m a n y Americans use popular diet books. Obesity, uncomplicated by other comorbidities, is not considered a reimbursable expense by m o s t insurance companies and health maintenance organizations. Therefore, a dieter m u s t usually pay out of pocket for all or most of the cost of treatment. Billions of dollars are spent each year o n obesity treatment, with charges ranging from m o d est to exorbitant. Unfortunately, there is n o C o n s u m e r Reports list that summarizes the effectiveness and costs of different programs. Standardized information, including disclosure of the effectiveness and cost of different approaches, is not available. Therefore, the buyer must beware. S o m e professional societies, such as local chapters of the American Dietetic Association, the American Medical Association, and the North American Society for the Study of Obesity, are good sources to consult if questions arise about a particular program.
Consumer Friendliness Health is a social good. T h e fact that health care, including obesity treatment, also represents a commercial transaction does not exempt it from the need for ethical and humanistic marketing and treatment practices. Therefore, consumers of obesity treatment programs have the right to be treated respectfully and with safe treatments. In the early 1990s, congressional hearings examined the misleading advertising claims used by s o m e commercial weight loss programs. A s a result of these hearings, the Federal Trade Commission recently encouraged commercial weight loss programs to voluntarily disclose their costs and results of treatment, so that consumers can m a k e informed decisions w h e n selecting treatment.
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This issue is reviewed in chapter 19 in this volume (see Womble, Wang, &c Wadden, Chapter 19). Coping with Coexisting Health Risks and Conditions O n e of the major problems with obese individuals' embarking o n weight loss diets by themselves is that they m a y have health complications that m a y go unrecognized or neglected. Diet books and programs should remind overweight persons of this potential concern. For this reason, those w h o wish to lose more than a few pounds should consult their physicians before spending m o n e y or time on a reducing regimen. Moreover, children, adolescents, pregnant and nursing w o m e n , persons with eating disorders, those suffering from depression, extremely obese individuals (i.e., those with a body mass index [BMI] > 4 0 kg/m^), and those w h o are not obese but feel they must lose weight should not go on diets of their o w n devising. Such individuals should always seek professional assistance.
Components of Sound V/eight Management At the very least, weight management requires a hypocaloric diet to lose weight, consisting of an eating plan that is lower in calories than the diet the individual consumed at his or her higher weight. It also includes a physical activity and exercise prescription, as well as psychological and social support. Finally, sound weight management requires that any weightrelated health complication be appropriately monitored (and treated).
Continuation of Provisions for Long-Term Maintenance It is m u c h easier to take weight off than to keep it off. During weight maintenance, energy intake must be somewhat lower than it was prior to embarking on the reducing diet, if the lowered weight is to be maintained. This is because some lean tissue is lost along with the fat, and as a result, R M R falls slightly. Also, moving a lighter body requires less energy, so total energy output decreases slightly. Success in maintaining weight loss is more likely w h e n the dieter is provided with information, tools, social support, and associated lifestyle behaviors to m a k e the long-term changes that are required. These include a reasonable eating pattern (such as one that follows the Dietary Guidelines for Americans and the U S D A ' s Food Guide Pyramid) and a program of regular physical activity. Psychological support, including remotivation, lapse and relapse prevention, cognitive restructuring, and behavior modification strategies, are also helpful to m a n y individuals.
A D V A N T A G E S A N D DISADVANTAGES O F REDUCING DIETS AT VARIOUS CALORIE LEVELS The caloric levels (and deficits) that are most appropriate for an individual depend on his or her health, the urgency of the medical problem, the severity of the overweight, the adequacy of medical supervision, and food preferences. For self-initiated weight loss, diets with smaUer energy defichs are the safest, the most likely to be nutritionally complete, and the most likely to produce lasting results. Diets providing fewer than 800 kcaVday definitely require stringent physician monitoring. Regardless of the caloric level, all medically appropriate diets should adhere to the seven C's described above. Popular diets today include total fasting; V L C D s and protein-supplemented modified
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fasts, which contain fewer than 800 kcal/day; LCDs, providing from 800 to 1,200 kcal/day; and more moderate hypocaloric reducing plans providing 1,200 kcal/day or more. Because the caloric level is so critical in determining the short-term effectiveness of weight reduction, the advantages and disadvantages of different levels are discussed briefly below.
Total Fasts Total fasting involves temporary starvation. It is associated with significant health risks, including (1) the excessive loss of lean tissue; (2) metabolic changes, such as ketosis and diuresis; and (3) electrolyte imbalances, including kaliuresis and saliuresis (Aoki & Finley, 1986). Losses of lean tissue cause R M R to fall. Voluntary physical activity also tends to decrease, since patients often feel lethargic, as well as dizzy, weak, lightheaded, or faint w h e n standing. These occurances result in decreases in energy output that slow weight loss. Exercise tolerance is greatly diminished, so that compensatory increases in physical activity are not advisable. Menstrual irregularity and hair loss m a y occur a m o n g some persons. Total fasts affect linear growth in children, and for all persons, they are insufficient in vitamins, minerals, protein, essential fatty acids, andfiberunless they are supplemented. Because of these complications, total fasting is not recommended for weight reduction under any circumstances.
Very-Low-Calorie Diets V L C D s , providing fewer than 800 kcal/day, are also below the R M R of virtually all adults; they have metabolic effects similar to those of total fasts, but these are usually less pronounced. T h e extent of the metabolic effects depends on the size of the negative energy balance induced. These regimens are sometimes referred to as "protein-supplemented modified fasts," since a large proportion of the energy they provide comes from protein. Compared to usual diets, the deficit is not balanced but unbalanced, with greater reductions in fat and carbohydrate than in protein. This is necessary because protein needs rise as energy intakes fall, and the presence of the glucogenic amino acids also provides an indirect source of carbohydrate (via gluconeogenesis) to help minimize ketosis. V L C D s are recommended for persons with a B M I > 30 kg/m^- The advantages of these diets include the ability to induce rapid weight loss w h e n the medical risks of obesity are so great that immediate action is needed. For individuals with significant medical complications, such as Type 2 diabetes mellitus, impaired pulmonary function, hyperlipidemia, and hypertension, as well as severely impaired mobility, these diets can be beneficial under appropriate medical supervision. The supervised treatment should also include assistance in developing a physical activity plan and in learning appropriate eating habits, once patients have completed the V L C D . Unless specially fortified products are used, muhivitamin and mineral supplements are needed. For w o m e n , iron and calcium supplements are also required. W h e n appropriately formulated and administered under close medical supervision to selected patients for reasonable lengths of time, V L C D s can be safe and effective in helping patients lose weight (Brodoff &C Hendler, 1992; National Task Force on the Prevention and Treatment of Obesity, 1993; W a d d e n & Bardett, 1992). However, the popular versions of V L C D s individuals administer to themselves often lack one or more of these prerequisites. Because drug metabolism and volume of distribution are altered, individuals w h o are taking medications often need them adjusted. T o avoid risks of cardiac problems associated with loss of lean body mass, which m a y include both arrhythmias and wasting of the heart muscle itself, the duration of a V L C D should be n o more than 12-16 weeks. Because most V L C D s are very low in carbohydrate and calories, and slightly ketogenic, patients are usually in negative water balance on them. During nonadherent periods or upon refeeding, they
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often gain large amounts of weight in a few days, due to restoration of water balance to more normal levels. Because V L C D s are so different from usual dietary intakes, instruction is necessary to avoid overindulgence w h e n a dieter returns to regular eating patterns. The characteristics and problems of V L C D s , as well as examples of popular diets based on them, are discussed elsewhere in greater detail (Dwyer & Lu, 1993; Kanders & Blackburn, 1994; National Task Force, 1993).
Low-Calorie Diets L C D s , providing 800-1,200 kcal/day, are stiU below the R M R for most adults, but they have less pronounced effects on metabolism than do V L C D s . M a n y meal replacement products, designed for use in L C D s , are n o w available in supermarkets and drugstores. Examples include SlimFast and Ultra SlimFast, as well as the Cambridge Food for Life Program. These products are specially formulated foods or powders that are designed as meal replacements; if label directions are followed, intakes should average approximately 1,1001,200 kcal/day. Deviation from these recommened levels could be associated with adverse consequences, as discussed later. Frozen low-calorie main dishes are also popular a m o n g dieters. These include Heahhy Choice, Ultra SlimFast Frozen Entrees, Weight Watchers entrees (e.g.. Smart Ones), Stouffer's Lean Cuisine, Budget Gourmet Light, and m a n y others. M o s t of them provide about 200-300 kcal/serving, are low in fat and cholesterol, are relatively high in carbohydrate, and vary in their vitamin and mineral contributions. All of these products provide convenient, portion-controlled, quick-to-prepare entrees that are useful adjuncts to a total weight management program. However, there is no guarantee that individuals will devise and follow an appropriate plan on their own. Therefore, some medical assistance is advisable. SimUar meals are sold as part of commercial weight loss programs, such as nutrisystem.com, Jenny Craig Weight Loss Centres, and Intelligent Cuisine. These products have the advantage of being part of broader and more comprehensive programs, but the total costs of the programs are also greater. Several commercial programs, including Weight Watchers, Diet Workshop, and Diet Center, also provide (or have provided) L C D s that use conventional (table) foods. M a n y of these regimens begin with a low-carbohydrate, hypocaloric diet of 900-1,000 kcal/day to stimulate diuresis and rapid weight loss in the first few weeks. Calorie intake is then increased to 1,200 kcal/day or more. Usually multivitamin and mineral supplements, and for w o m e n calcium and iron supplements, are recommended. M o s t of the programs also include group support, some nutrition education, and a program of physical activity. Books that advocate L C D s are also plentiful. "Unbalanced-defich diets" are currently popular. Deficits in calories are accompanied by a radical redistribution of the energy-providing nutrients to emphasize low carbohydrate, high protein, and relatively low fat, in comparison to usual dietary intakes. The advantages of such regimens are that they are novel; the energy level is usually low enough to cause weight loss, but not so low as to induce troublesome metabolic side effects; and they stimulate a rapid diuresis with welcome loss of weight, albeit water weight. This m a y encourage dieters to continue their efforts. Several such diets are discussed below, and others are analyzed elsewhere (Dwyer, 1992; Dwyer & Lu, 1993).
Balanced-Deficit Diets Diets that provide 1,200 kcal/day or more and are suhably formulated are probably the most benign if not the most popular of the self-prescribed diets that Americans undertake.
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They are sometimes referred to as "balanced-defich diets." They tend to be lower in c but have a "balanced" profile of calories that provides nutrients and foods closer to the profile recommended for good health among nondieters. That is, they are relatively low in fat (<30% calories), high in complex carbohydrate (>55% calories), moderate in protein (10-15% calories), devoid of or very low in alcohol, and high infiber(25-30 g/day). Various nutritionally adequate well-planned regimens are available. They include the regimens recommended by nonprofit weight loss groups, by professionals such as registered dietitians, and by most programs based in hospitals or health centers (other than the V L C D programs). Balanced-deficit diets may also be offered by commercial programs such as the Diet Center, Physicians' Weight Loss Centers, and Weight Watchers. For those w h o cannot afford such programs, two self-help programs. Take Off Pounds Sensibly (TOPS) and Overeaters Anonymous (OA), may be helpful. Several popular diet books also promote reasonable, moderately-low-calorie diets. These books include The Callaway Diet (Callaway with Whitney, 1990), The T-Factor Diet (Katahn, 1989), and The Fat Attack Plan (Natow ScHeslin, 1990). The higher calorie levels of balanced-deficit diets (relative to V L C D s and LCDs) make compliance easier, minimize undesirable metabolic side effects, eliminate the need for special foods, and permit dietary and eating reeducation to occur during the weight loss process. In addition, exercise tolerance is good on a balanced-deficit diet. A n aerobic exercise program can be a helpful adjunct to counteract the decrease in R M R induced by a hypocaloric diet and to further increase weight loss without excessive dietary deprivation. Furthermore, loss of metabolically active tissue is minimized when the weight loss strategy includes exercise (Marks, Ward, Morris, CasteUani, & Rippe, 1995). The major disadvantage of balanced-deficit diets is that weight loss is somewhat slower than on the more drastic regimens, and thus motivation, patience, and adherence may be low. The key to success, as it is on any weight loss program, is adherence. To facilitate adherence, some regimens restrict choice to a preplanned menu or an exchange plan that allows a dieter to select only certain alternatives. Other regimens restrict choice to a set menu. For these approaches, one should always be sure that no major food group is completely excluded. In addition, dieters should choose the dieting approach that best suits their needs and preferences.
DIET B O O K S A N D R E G I M E N S Diets Based on the Glycemic Index The "glycemic index" (GI) is a dietary concept that has become very popular recently. The GI describes the blood glucose response resulting from consumption of a defined amount of carbohydrate (usually 50 g) from a given food, relative to the same amount of carbohydrate from a control food (Wolever, Jenkins, Jenkins, & Josse, 1991). The control food may be pure glucose or white bread, ahhough the latter is preferred due to problems with osmolarity of glucose solutions. The GI concept wasfirstdeveloped as a strategy to help guide patients with diabetes in maintaining stable blood glucose. The pros (Brand-Miller & FosterPoweU, 1999; Wolever, 1999) and cons (Beebe, 1999; Franz, 1999) of its applicability are still being discussed in the literature. Recently the GI has been suggested as a tool for the treatment and prevention of overweight and obesity (Ludwig et al., 1999).ftis purportedly the basis for the diets outlined in the books Dr. Bob Arnot's Revolutionary Weight Control Program (Arnot, 1998) and The Glucose Revolution (Brand-Miller, Wolever, Colagiuri, & Foster-Powell, 1999). Other, less
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balanced diets involving the GI, including those decribed in the books Sugar Busters! (Steward, 1999), The Montignac Method (Montignac, 1999b), and Dr. Atkins' N e w Diet Revolution (Atkins, 1999), are discussed in later sections. The premise is that foods whose consumption triggers a rapid, high peak in blood glucose (high-GI foods), and subsequently a surge in insulin secretion, will cause a rapid drop in blood glucose—below levels prior to consumption of the food. This is purported to result in a more rapid return of hunger, compared to foods that produce a more moderate blood glucose response (Ludwig et al., 1999; Melanson, Westerterp-Plantenga, Saris, Smith, & Campfield, 1999). At least in the short term, this lack of satiety m a y drive up energy consumption, leading to weight gain. S o m e studies have shown enhanced satiety and/or lower voluntary energy intake with consumption of low-GI foods or meals (Holt, Brand, Soveny, & Hansky, 1992; Ludwig et al, 1999; V a n Amelsvoort & Weststrate, 1992). Other investigations, however have not (Hoh, Brand-MUler, &c Petocz, 1996; Kovacs, Brouns, Melanson, & Westerterp-Plantenga, in press). Research has been hampered by the lack of well-validated tools for measuring satiety over both the short and long term, but such tools are n o w being developed (Green, Delargy, Joanes, & Blundell, 1997). S o m e energy-restricted low-insulinemic diets have been shown to produce better weight losses than higher-insulinemic diets (Slabber, Barnard, Kuyl, Dannhauser, & SchaU, 1994), but not in aU cases (Jenkins et al., 1987; Wolever et al., 1991). Since satiety is only one of m a n y components determining food consumption, the influence of the GI on other components should also be investigated. "Satiety" is related to the duration of intermeal intervals and meal frequency; it refers to hunger inhibition following food consumption (Melanson, Westerterp-Plantenga, Campfield, & Saris, 1999). In contrast, "satiation" refers to the inhibition of hunger during meals; it is related to meal termination and meal size. Although low-GI foods m a y induce more satiety than high-GI foods, they m a y not affect satiation. O n e study found longer intermeal intervals following low-GI versus high-GI preloads, but no differences in subsequent food intakes (Melanson, Westerterp-Plantenga, Saris, et al., 1999). M o r e research is needed on this issue.
Foods with hiigh and Low GIs The GIs of over 600 different foods have been tested. Factors that determine the GI of a given food or meal include type and amount of carbohydrate, physical form, particle size, fiber content (i.e., soluble and insoluble), protein, fat, and degree of cooking and food processing (e.g., monosaccharides, amylose and amylopectin content of starch, degree of gelatinization of starch, resistant starch). Low-GI foods are slowly digested and absorbed, producing a more gradual postprandial rise in blood glucose than high-GI foods. These low-GI foods are generally high in fiber (including whole grains such as steel-cut oats, legumes, pumpernickel bread, and pasta), but they also include dairy products and some confections. Foods with a high GI include potatoes, carrots, white rice, white bread, and some refined sugars. Amylose has a higher GI than amylopectin. N o t all sugary foods have a high GI, probably due mainly to their fructose content. Fructose consists of one glucose and one galactose unh. However, honey ( 5 0 % fructose as invert sugar) does have a high GI. If the starch in a food is fully gelatinized, that food can be rapidly digested and absorbed as glucose units; thus the GI is high. However, these distinctions in food chemistry m a y not be readily apparent to consumers. Method of preparation can also influence the GI of some foods but not of others. For example, steel-cut oats have a lower GI than instant oatmeal, and raw carrots have a lower GI than cooked carrots (Gustafsson, Asp, Hagander, N y m a n , & Schweizer, 1995). Formally, h was thought that combining foods of different GIs did not yield the average of their GIs (Coulston, HoUen-
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beck, & Reaven, 1984). Subsequent data, however have chaUenged this notion (Chew, Brand, Thorburn, & Truswell, 1988; Hermansen, Rasmussen, Arnfred, Winther, & Schmitz, 1988). Foods within the same conventional food group can have markedly different GIs. For example, cornflakes or Wheatabix breakfast cereals have higher GIs than AllBran or Muesli; white potatoes have a higher GI than sweet potatoes; carrots have a higher GI than peas; watermelon has a higher GI than peaches; and jelly beans have a higher GI than M & M s .
Practical Shortcomings of the GI Concept
With over 600 foods tested, and several thousand more foods on the market and in rest rants, the concept of glycemic index may be difficult for American consumers to deal with on a daily basis. If it were to be put into practice as a weight management tool, patients would have to be equipped with GI tables and learn strategies for substituting low-GI foods for high-GI ones. Although this is not impossible, it would involve significant patient education. Before the GI is used as a weight loss strategy, more research should be conducted on its long-term efficacy and applicability. It is important to determine whether energy compensation occurs over time in ad libitum situations on low- and high-GI diets. Any diet needs to be viewed as a whole. Focusing on one aspect of the diet—whether it is the GI, sugar, carbohydrate, fiber, protein or fat—is not a solution in itself. Of course, total energy intake and portion size are just as important in applying the GI as they are in any weight loss strategy. Although a low-GI diet can be high in whole grains, beans, and vegetables, it also may be high in protein and in saturated and other fats. Certainly, one should not substitute potato chips for boiled potatoes, or M & M s for watermelon, or sausage for carrots, based solely on the GI. Furthermore, one should not exclude nutrient-rich foods from the diet on this basis. A diet low in simple sugars and high in whole grains, fruits, and vegetables is desirable. The World Health Organization (1998) recommends that no more than 1 0 % of dietary energy come from simple sugars. If consumption of foods with high GIs drives up total energy consumption, than a weight control regimen low in these foods is prudent. However, if the GI concept leads to an overconsumption of fat and protein, and to the exclusion of important nutrient sources, then it is being used inappropriately. Health could be compromised, and weight loss is unlikely.
High-Protein Diets A popular diet that reappears in different forms every few years is the high-protein, lowcarbohydrate plan. Some variants are also quhe high in fat. Many best-selling diet books promote this type of diet, including Sugar Busters! (Steward, 1999), The Carbohydrate Addict's Diet (Heller &c Heller, 1999b), The Zone (Sears with Lawren, 1995), Protein Power: The Metabolic Breakthrough (Fades, 1996), and Dr. Atkins' N e w Diet Revolution (Atkins, 1999). These types of diets are not recommended because they are based on false assumptions about metabolism, are lacking in sufficient carbohydrate and some micronutrients, and advocate intakes of protein and fat that are potentially harmful. Some books go so far as to say that carbohydrate is "poison" and is not required by the human body. The fact remains that carbohydrate is an essential macronutrient; the central nervous system relies on its continuous availability. A minimum of 50-100 g of carbohydrate should be consumed daily to sustain the central nervous system, as well as to prevent rapid protein degradation and large shifts in weight due to changes in water balance. Some high-protein diet plans advocate consumption of 4 0 % of dietary energy as carbohydrate, 3 0 % as fat, and 3 0 % protein (i.e., the "40/30/30 plan"). The theory behind these
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diets is that carbohydrate consumption in excess of this stimulates the release of insulin, an anabolic hormone that functions to promote the storage of metabolic fuels, thus leading to weight gain. This is an oversimplification of very complex metabolic processes. T h e crucial fact that is missing from the theory is that metabolic fuels will only be stored under conditions of energy surplus, not during an energy deficit. Insulin itself will not promote body fatness if there is no energy available to be stored. T h e reasons these diets w o r k are their energy deficits (most provide about 1,200 kcal/day or less) and the fact that they are ketogenic and lead to a state of relative dehydration. Weight loss is not the result of alterations in insulin metabohsm that the diets engender. In the absence of medical supervision, any diet that promotes a state of ketosis should be avoided as potentially dangerous. Even if these diets lead to initial loss of relatively large amounts of water, they should not be encouraged because prolonged adherence to highprotein diets m a y lead to calcuria, to kidney stones in those w h o are prone to them, and to high blood urea nitrogen in those with undiagnosed kidney problems. T h e increased nitrogenous load caused by the combination of high protein intake and a high rate of gluconeogenesis results in an elevated obligatory urine volume, and thus m a y lead to dehydration. This can have deleterious effects on physical and mental health. However, dieters m a y perceive the weight loss associated with dehydration as beneficial, and thus m a y think the diet is particularly effective. This m a y be a factor in the popularity of high-protein diets. High-protein diets are often high in fat and in saturated fat, and because high-saturatedfat diets are well established as atherogenic, they are inappropriate over the long run. In addition, m a n y high-protein, very-low-carbohydrate plans have lists of "forbidden foods" that include potatoes, pasta, rice, white bread, bagels, carrots, corn, and watermelon. This is one reason w h y the diets m a y be lacking in such nutrients as calcium, magnesium, manganese, and potassium; the B vitamins; dietary fiber; and water. Vitamin D levels, as well as calcium, m a y be low if milk products are prohibited because of the lactose (a sugar) they contain. M a n y professional organizations, including the American College of Sports Medicine, the American Dietetic Association, the W o m e n ' s Sports Foundation, and the Cooper Institute for Aerobics Research, have all issued statements that high-protein plans are the answer neither for weight loss nor for improving athletic performance. Indeed, they can cause harm. A n important aspect of any weight loss regimen is that it must provide strategies for maintenance of weight loss after a healthier weight is achieved. This is critical, considering the extremely high relapse rates as individuals m o v e from weight loss into weight management (Pasman et al., 1999). In order to prevent weight regain, permanent changes in diet and lifestyle must be learned and adopted. Long-term adherence (i.e., over several months) to a low-carbohydrate, high-protein diet that is also high in fat and saturated fat could pose significant health risks, as previously described. Furthermore, the protective effects of a diet high in whole grains, fruits and vegetables, soluble and insoluble fiber, and antioxidant nutrients would be missed. This could increase the risk of a number of chronic degenerative diseases, including certain cancers and diverticulosis. Long-term data on the effectiveness and safety of 40/30/30 plans are lacking, but because the risks associated with high-protein and high-fat diets in general are well established, these diets are not recommended. The fact that a high-protein, low-carbohydrate diet does not teach healthful lifelong eating habhs is a strong argument against such a regimen. Low-Protein Diets Fortunately, low-protein diets are not presently in vogue. Low-protein regimens are a serious concern, because protein needs are higher in hypocaloric states than they are in energy
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balance. As noted earlier, significant health risks and undesirable metabolic effects are associated with insufficient protein intake during weight loss. Protein deficiency can result in hair loss, lethargy, exercise intolerance, edema, fluid and electrolyte imbalances, cardiac and kidney problems, depressed immunity, and skin abnormalities. These diets m a y also be lacking in vitamin B12, zinc, calcium, and some fat-soluble vitamins. Recommendations for appropriate amounts of protein are provided in preceding sections. High-Fat Diets The /V\ontignac /Aethod A weight loss strategy particularly popular among upper-class Europeans is the Montignac Method, created by the French chef Michel Montignac (Montignac, 1999a, 1999b). The diet includes foie gras, creme brulee, souffle, chocolate truffles, and wine daily. However, fat and carbohydrate are not permitted at the same meal because (according to the plan's "metabolic synopsis") increases in blood glucose cause fat to be stored in the body. T h e author states that hyperinsulinemia is the cause of obesity rather than a consequence. This is an erroneous, oversimplified interpretation of the relationship and the direction of causality. If the diet does cause weight loss, it is because the diet is hypocaloric, not because it plays "metabolic tricks." Perhaps the appeal of the intriguing French cuisine enhances adherence. According to Montignac's theories, individuals can lose weight and become healthier without restricting quantities of food intake, exercising, or being concerned about dietary fat and cholesterol. O n e part of the rationale is that French people are thin despite a rich diet. Montignac claims that habits such as eating the biggest meal at lunchtime rather than at dinner and avoiding snacks between meals must be responsible. This correlational evidence cannot prove causality. Clearly, other lifestyle factors (including habitual physical activity) play roles in determining levels of adiposity. Another part of the Montignac plan is based on the GI, listing "bad" and "good" carbohydrates. A n y food with a GI above 50 is forbidden. This is arbitrary, because m a n y GI lists have very different values for the same foods. Thus a food m a y be "good" according to some Usts and "bad" according to others. Furthermore, m a n y of the foods on the "bad" lists are nourishing foods that are rich in vitamins, minerals, and fiber. Examples include carrots, beets, potatoes, corn, rice, popcorn, rice cakes, watermelon, bananas, raisins, and cantaloupe. These foods do not deserve a bad name. As indicated earlier, lists of "bad" and "good" foods are warning signs that a diet is unreasonable, especially if fruits and vegetables are considered "bad" foods. The Atkins Diets The popular Atkins diets (Atkins, 1981, 1992, 1999), which are also high in fat (and low in carbohydrate), encourage a state of ketosis. In fact, dieters are told that they are doing something wrong if they are not ketotic; they are told to stimulate ketosis. According to Atkins, the best diet is high in fat and moderate in protein, with zero carbohydrate. Parts of this diet include 20 g of carbohydrate daily. This low level causes extreme ketosis, which can be hazardous, especially in the absence of medical supervision. Furthermore, these types of diets are lacking in several vitamins, antioxidants, and calcium. In addition to being potentially threatening to cardiovascular health, these regimens do not teach a proper lifelong diet.
Low-Carbohydrate Diets Low-carbohydrate diets c o m e in m a n y forms, but should not be recommended under most circumstances. Carbohydrate levels are important in L C D s , because adequate carbohydrate
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is necessary to maintain blood sugar levels and fluid balance. At levels of more than 100 g/day, both of these functions can be accomplished. At levels of carbohydrate below about 100 g/day, insulin levels fall and protein must be catabolized to provide glucogenic amino acids to keep blood sugar at normal levels. The brain requires about 100 g of glucose as fuel a day, and other tissues use about 50 g. Thus, at any carbohydrate level below 100 g/day, ketosis is likely, at least initially. The m i n i m u m carbohydrate requirement is thought to be at least 50 g/day, even after adaptations have occurred. Fifty grams of carbohydrate are provided in about 2 potatoes, 4 slices of bread, or 4 tablespoons of sugar. Over time some adaptations can be m a d e in carbohydrate needs as insuhn-glucagon ratios induce adipose tissue breakdown, causing body cells to burn more and more fatty acids. However, some tissues cannot do this, and these must rely on glucose supplied either exogenously or from proteolysis of lean tissue such as muscle. W h e n protein is burned to preserve blood sugar levels, additional water is hberated by the process of protein catabolism. A diuresis and loss of fluid weight follow quickly in thefirstfew days on a diet (VanltaUie & Yang, 1977). M o s t authorities recommend a carbohydrate intake of approximately 100 g/day, preferably from complex carbohydrate which is often also high in healthful dietary fiber and m a y promote satiety (Raben, Jensen, M a r c k m a n n , Sandstrom, & Astrup, 1995). A dieter w h o uses a low-carbohydrate, low-calorie regimen needs to be aware of the sudden shifts in water balance that m a y occur if the individual goes "off the diet" or otherwise greatly increases carbohydrate intake. Such shifts m a y consist of as m u c h as 5-10 pounds of edemafluid.The edema is due to the rapid reversal of the glycogen depletion and dehydration that are c o m m o n on V L C D s . During refeeding or bingeing, w h e n carbohydrate intakes increase, glycogen and its water of hydration suddenly accumulate, with consequent rapid weight gain (often with rapid, sharp upward spikes in weight). These shifts can be prevented by increasing carbohydrate and energy intakes gradually. High-Carbohydrate Diets Diet books that promote high-carbohydrate, low-fat, and moderate-protein food intake plans are generally well balanced and safe, particularly if the carbohydrate sources include plenty of vegetables, fruits, and whole-grain foods. A s with all weight loss programs, every food group should be included each day, and there should be no forbidden foods. Such books include Eat More, Weigh Less: Dr. D e a n Ornish's Life Choice Program for Losing Weight Safely (Ornish, 1997), The Fit or Fat Target Diet (BaUey, 1984), The T-Factor Diet (Katahn, 1989), and The T-Factor 2000 Diet (Katahn with Pope, 1999). However, any diet that promotes extremely low caloric and/or fat intake should be approached with caution. Prolonged adherence to fat intakes in the range of 1 0 % or less of energy intake can cause endocrine problems such as amenorrhea. Extremely low-fat diets can lead to deficiencies in essential fatty acids and reduced absorption of the fat-soluble vitamins (A, D, E, and K). Diets providing 800-1,200 kcal/day should supply at least 5 5 % of energy from carbohydrate. With a daily intake of 1,200 kcal or more, at least 5 5 % - 6 5 % complex carbohydrate is desirable. These levels can be beneficial as weight loss regimens, particularly because of their highfibercontents, which help to sustain satiety. For example, in Eat More, Weigh Less, Ornish emphasizes feeling full from whole grains, vegetables, and fruh. His diet's total weight and volume are high, and these factors are thought to foster satiety. O n such a high-bulk diet, one must remember to consume large quantities of water to help keep intestinal contents soft. This book and others by Ornish also emphasize an overaU lifestyle approach, which includes exercise and other behavior change to facilitate lifelong weight maintenance. This approach, w h e n foUowed appropriately, has also been associated with decreases in cardiovascular risk factors.
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Barbara Rolls has recently published a book titled Volumetrics: Feel Full on Fewer Calories (RoUs & Barnett, 1999). Similar to Ornish's approach, RoUs's plan emphasizes consumption of foods with low energy density to promote satiety. Data from her lab and others have s h o w n that food intake is regulated more by weight and volume of food than by energetic content, at least in the short term (KendaU, Levhsky, Strupp, & Lissner, 1991; Lissner, Levhsky, Strupp, Kalkwarf, & Roe, 1987; Rolls & H a m m e r , 1995; Saltzman, Dallal, & Roberts, 1997; Stubbs, Harbron, Murgatroyd, & Prentice, 1995). Freely feeding individuals w h o consume food to the point of physiological satiety are likely to eat less total energy from a meal with low energy density than from a meal with high energy density. This is independent of macronutrient content (Rolls, 1995; Rolls, BeU, & Thorwart, 1999), which was controlled for in these studies, since fat is the most energetically dense macronutrient. Foods with a high water content, such as fruits, vegetables, and soups, have low energy density, so the Volumetrics book recommends consumption of these foods and offers recipes to prepare them. The book emphasizes that drinking water alone is not enough to sustain satiety, thus displacing a widely held notion popular a m o n g dieters for decades. Although water's inability to substantially suppress appetite is evidenced by research (Rolls et al., 1999), its importance in supporting health in all individuals, particularly dieters, should be stressed. Foods high in fiber also have low energy density, and as previously discussed, high-fiber diets should be accompanied by high fluid intake to maintain laxation. Since the Volumetrics book encourages intake of plenty of fruits, vegetables, and nourishing soups, it is health-promoting. Furthermore, the book includes sections on increasing physical activity, learning to avoid environmental cues that m a y trigger excess food intake, and developing a healthful lifestyle. However, since most of the studies on dietary energy density and food intake regulation have been short term and have been conducted with lean individuals, the enduring effects of a weight loss regimen based on this concept remain uncertain. A n important consideration is that not all individuals eat according to physiological hunger and satiety signals, but often eat according to other external cues. This m a y be particularly true of the overweight and obese individuals w h o m a y be interested in this weight loss strategy. Cross-sectional population studies have shown inverse relationships between body weight and the consumption of fruits and vegetables (McCrory et al., 1999). Longerterm studies should be conducted with obese individuals to determine whether energy intake compensation eventually occurs with the consumption of a low-energy-density diet within this population. The Pritikin diet h o o k s — T h e Pritikin Weight Loss Breakthrough (Pritikin, 1999), The N e w Pritikin Program (Pritikin, 1990), and Beyond Pritikin (Gittieman & Desgrey, 1996)—also encourage a high consumption of fruits, vegetables, and whole-grain breads and cereals, as well as other healthful lifestyle changes. However, these books should be approached with some caution, since the 1,000-kcal (women) and 1,200-kcal (men) diets do not take individual needs for weight loss into account. The 1 0 % fat, 7 5 % - 8 0 % carbohydrate levels m a y be difficult for most dieters to adhere to over the long term. The T-Factor Diet (Katahn, 1989) and The T-Factor 2 0 0 0 Diet (Katahn with Pope, 1999), which suggest only 20-40 g of fat daily for w o m e n and 30-60 g of fat for m e n , m a y also be difficult to adhere to, but offer slightly more balanced food choices than the Pritikin books do. The Fit or Fat Target Diet (Bailey, 1984) emphasizes a healthful balanced diet that includes aU food groups, but provides few suggestions for behavior modification that would facilitate weight loss. In general, weight loss diets providing 5 5 % - 6 5 % complex carbohydrate teach healthy eating habits that can help to maintain weight loss. A n important point to bear in mind is that the preferred carbohydrate sources are starches andfibers,not simple sugars. A n added
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benefit is that whole grains, fruits, and vegetables have also been implicated in the prevention of heart disease and some cancers.
Other Diet Books In recent decades, numerous weight loss plans have been published, some more reasonable and sound than others. S o m e books that offer less sound or otherwise inappropriate diets include Eat Right 4 Your Type (D'Adamo, 1997), The N e w Beverly Hills Diet (Mazel with Wyatt & Sokol, 1996), The 5-Day Miracle Diet (Puhn, 1996), Fit for Life (Diamond & Diamond, 1985), The Hilton H e a d Over-35 Diet (MiUer, 1989), and The Rotation Diet (Katahn, 1987). These have been reviewed in detaU elsewhere (Burland, 1986; Dwyer & Lu, 1993). Eat Right 4 Your Type (D'Adamo, 1997) is a weight loss plan based on blood type, which is scientifically unfounded, lacking in research to substantiate the author's claims, and unduly limited in the foods it permits. The regimen described in The N e w Beverly Hills Diet (Mazel et al., 1996) restricts different food groups at different times of day, based on erroneous assumptions about the metabolism of certain combinations of foods. Moreover, this diet does not account for individual differences in energetic needs. Puhn (1996), in The 5-Day Miracle Diet, describes a potentially dangerous V L C D (800 kcal/day) w h e n self-administered without medical supervision. Although the diet's recommended duration is only 5 days, the likelihood that people will follow it longer, or repeatedly, is almost certain. This probability is high because such a diet sets one up for failure, so a dieter tends to attempt it repeatedly. M o s t of the early weight loss probably consists of water, and it is unlikely to be maintained. The diet described in Fit for Life (Diamond & Diamond, 1985) should likewise be avoided, since it excludes some food groups and lacks variety, which is necessary for adherence. In addition to this diet's being high in fat ( > 4 0 % ) , its metabolic basis is unfounded; the authors claim that fat deposits result from improper food combinations. Diets that advocate variations in energy intakes in order to prevent declines in R M R are also based on unfounded assumptions for which there is no ample scientific evidence. In fact, if they lead to weight cycling, decreases in percentage of lean tissue can result, leading to depressions in metabolic rate that m a k e further weight loss attempts more difficult. These include the regimens outlined in The Hilton H e a d Over-35 Diet (MiUer, 1989) and The Rotation Diet (Katahn, 1986). Both of these diets are also lacking in some of the food groups.
Weight Loss Books with Less Diet Emphasis Weight loss books recommending sound nutrition and lifestyle changes to promote healthful habhs and strategies for weight maintenance include The Solution (Meillin, 1997), Intuitive Eating (Tribole & Resch, 1995), Habits, N o t Diets: The Secret to Lifetime Weight Control (Ferguson & Ferguson, 1997), The Complete Idiot's Guide to Losing Weight (McQuiUan, 1998), and Dieting for D u m m i e s (Khby, 1998). The Solution (MeUlin, 1997) describes a nondiet approach that focuses on addressing the underlying causes for obesity or overweight, not the symptoms. It encourages the reader to understand w h y he or she overeats and to address those issues. This m a y be a good book for chronic dieters. Intuitive Eating (Tribole & Resch, 1995) instructs readers to listen to internal hunger and satiety signals as cues for food ingestion rather than being controlled by external cues. This is potentially a good book for individuals w h o binge-eat, or w h o eat in response to circumstances such as stress, loneliness, boredom, or depression. Habits, N o t Diets (Ferguson & Ferguson, 1997) promotes the use of such tools as food intake and activity journals and self-evab nations. Teaching commitment to change and self-disciphne, this book's structured ap-
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proach may not be for everyone, but its underlying principles are sound. The Complete iot's Guide to Losing Weight (McQuiUan, 1998) and Dieting for Dummies (Kirby, 1998) are weU-rounded books that include sensible weight loss strategies, tips for spotting fraudulent fad diets, and healthy approaches to long-term lifestyle changes promoting weight maintenance. It should be noted, however, that the approaches described above are supported by minimal or no data. A thorough review of nondieting approaches to weight control is provided by Foster and McGuckin in Chapter 24 of this volume.
DIET F O O D S A N D P R O D U C T S Powdered-Diet Formulas and Meal Replacement Products Over-the-counter diet products have a place in weight reduction strategies, but they lend themselves to misuse, especially if consumers do not follow label directions. The oldest such product was Metrecal, a milk-based, low-kilocalorie meal replacement that was popular in the 1960s. Later, SlimFast, Ultra SlimFast, and similar powdered-diet formulas were placed on the market. Recently these products have become available ready-prepared in single-serving cans. The manufacturers of these products recommend the replacement of breakfast and dinner with one of their shakes (the powders are mixed with low-fat milk or water). These shakes are supplemented to include most of the daily required micronutrients (as weU as fiber, in the case of Ultra SlimFast), and provide 190-220 kcal. In addition to the meal replacements, manufacturers recommend that dieters consume one piece of fruit and a low-calorie dinner (about 410 kcal), for a total daily energy intake of 1,100-1,200 kcal. Instructions are included with the meal replacement products. If these are followed incorrectly, however, the results could be hazardous, especially in the absence of medical supervision. Some dieters believe that they can be more ambitious than the instructions suggest and try to restrict themselves more than is recommended. This can lead to micronutrient deficiencies, undesirable metabolic effects (as described earlier in regard to severe hypocaloric intakes), dietary imbalances, and an accumulation of hunger that can lead to subsequent overconsumption. The rationale behind these meal replacement weight loss products is that because they are monotonous and measured, they relieve the dieter from having to make daily food choices. If the number of kilocalories and sufficiency of micronutrients are already accounted for by the manufacturer, then a step is saved for the dieter. However, this does not teach proper dietary habits, since once the diet is over, the dieter must learn to choose appropriate breakfast and dinner items that contain the appropriate amounts of kilocalories and micronutrients. Newer diet formulas have come onto the market in recent years, which promise a quick start to the dieting process. These include such products as SlimFast's Jump Start, which suggests the consumption of three meal replacement shakes (210 kcal each) plus two pieces of fruit and a salad as the daily consumption. Thus this regimen qualifies as an L C D , but since the product is purchased over the counter, it could be dangerous in the absence of medical supervision. The SUmFast Jump Start meals are sold as 5-day kits, and are much more costiy than their longer-term counterparts. Statements such as "Lose 5 pounds in 5 days" are listed on the label. If this loss was aU body fat, it would requhe a defich of 3,500 kcal/day. Thus, if a person were to consume the suggested maximum of 1,000 kcal/day, an expendhure of 4,500 kcal in some other manner such as physical activity would be required for the claim to be true. A person would have to be abnormally active and/or large in order to expend so much energy daily. Obviously, the major weight loss on such a diet is mostly
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water and glycogen, not body fat. Water weight returns upon refeeding and restoration of glycogen stores.
Meal Replacement Bars Meal replacement bars have appeared on the market as alternatives to meal replacement shakes. These include ShmFast and Pounds-Off bars. Like meal replacement shakes, these bars contain about 200 kcal apiece, and are supplemented with certain micronutrients. However, some of these bars are sold individually with little or no dietary advice or instructions. Their labels m a y state that the bars should replace breakfast and lunch, and that a normal dinner should be consumed. Providing the dieter with httle guidance, this approach can be either hazardous or useless. If the dieter were to consume one of these bars in place of breakfast and lunch for a total of about 4 2 0 kcal, then he or she would be ravenous by dinnertime. If the dieter were to succumb to the natural feelings of hunger, it is possible that a dinner of excess calories would be consumed, defeating the purpose of the diet. The opposite scenario is also possible; that is, an overly ambitious dieter m a y consume a dinner of 400 kcal or less, in the caloric range of a V L C D or L C D , which can be potentially hazardous w h e n unsupervised. Like meal replacement shakes, these bars also do not teach lifelong healthy eating habits. Another type of meal replacement bar accommodates individuals w h o are following high-protein, low-carbohydrate diets. These include several brands of bars that aU contain proportions of the macronutrients in the range of the high-protein plans described earlier. The labels on these bars also contain little nutrition advice, and so they are particularly prone to misuse, especially if they are used as the sole source of nourishment. The bars are too low in carbohydrate, too high in protein, and potentially too hypocaloric for a sound reducing regimen to be composed solely of them.
Prepared Low-Calorie Meals An increasingly popular trend in weight loss products for self-initiated efforts is the availability of frozen low-calorie main dishes, n o w widely available in grocery stores and supermarkets. These items are preportioned so that the dieter can consume a mixed meal with a fixed and k n o w n amount of energy, fat, and other nutrients. As noted earlier, such products include Heahhy Choice, Ultra SlimFast Frozen Entrees, Weight Watchers (e.g.. Smart Ones), Stouffer's Lean Cuisine, and Budget Gourmet Light, a m o n g others. These frozen low-calorie products usually provide about 200-300 kcal/serving (Ultra SlimFast Frozen Entrees provide 230-400 kcal) from a variety of recipes. M o s t of the dishes are low in fat and cholesterol and relatively high in carbohydrate. They vary in their vitamin and mineral contents. Since these meals are convenient and quickly prepared, they can be useful as adjuncts to a total weight management program. However, the potential for abuse is present, as it is with other products for self-initiated weight loss efforts. In addition, these entrees are relatively expensive.
Low-Fat, Low-Sugar, and Low-Calorie Products Table 12.3 provides a description of some of the many products that are modified to be low in or devoid of calories. Throughout the 1990s, literally thousands of reduced-fat, low-fat, and fat-free foods were introduced to the U.S. market. These foods include cookies, crackers, soups, salad dressings, cheese and meat products, entrees, and m a n y more. Data have
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T A B L E 12.3. S o m e Sugar Alternatives and Fat Replacers (Not All Currently Approved in the United States) Ingredient
Comments
High-intensity noncaloric sweeteners
Noncaloric, sweeter than sugar; vary in bulk.
Acesufame K (acesulfame potassium). Brand names: Sunnet food ingredient and Sweet One, Swiss Sweet, and Twinsweet (acesulfame K-aspartame combination) tabletop sweeteners. Aspartame. Brand name: Nutrasweet.
Contains potassium, but content is insufficient to cause concern in persons with diabetes.
Sucralose. Brand name: Splenda.
N o effect on insulin secretion, glucose, or fructose absorption; bulk and heat stability provide useful functional qualities in baked goods.
Saccharin
Some consumers can detect bitter taste. Saccharin-aspartame blends are sometimes used.
Cyclamate
N o t approved currently in the United States. Often used in blends with saccharin.
Altitarame
N o t approved in the United States.
Polyols (sugar alcohols): Sorbitol, isomalt, lactitol, mannitol, xylitol, maltitol syrup, polydextrose, specific sugar names, hydrogenated starch hydrolysate mixtures, hydrogenated glucose syrup. Brand names include Lycasin, Hystar, Neosor, Letisse, StaLite.
Occur in certain plants, but are usually manufactured from mono-, di-, or polysaccharides for use as food ingredients. N o t as sweet as sugar. Most polyols are incompletely absorbed, providing from 1 to 4 kcal/g. Polyols do not elevate blood glucose and insulin levels. If polyols are used between meals in products such as cough drops, candy, chewing gums, or other betweenmeal snacks, their glycemic response is less. They m a y be useful alternatives for handling blood glucose fluctuations between meals. These products do not help restore blood glucose levels in hypoglycemia. W h e n they are consumed as part of a meal, blood glucose effects are less apparent, since other foods buffer or dilute the differences in glycemic response. Consumption of very high amounts of some polyols m a y cause laxative effects or other gastrointestinal discomfort.
Natural sweeteners
Naturally occurring in plants. Incompletely absorbed and so are lower in calories (2 kcal/g) and have lower glycemic effects than other nutritive sweeteners.
Steviodose
N o t presently approved in the United States.
Glycyrrhizen
Used as licoriceflavoring,but not approved for use as a lowcalorie sweetener in the United States. In very large amounts, m a y increase blood pressure.
Carbohydrate-based fat replacers
Provide carbohydrate, which varies in its bioavailability.
A n alert that the product contains phenylalanine is required in the United States so that persons with phenylketonuria can avoid it.
Derived from cereals, grains, and starches. They hold up to three Carbohydrate polymers: times their weight in water, provide 1 kcal/g w h e n hydrated, and Maltodextrin, corn syrup solids, vary in amounts of carbohydrate. starch, hydrolyzed cornstarch, modified food starch, polydextrose. Brand names: Maltrin, Lycadex, Paselli Excell, Stelar, N-Oil, Sta-Slim, Oatrim. (continued)
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T A B L E 12.3. continued Ingredient
Comments
Carbohydrate-based fat replacers (cont.) HydrocoUoids (gums, gels, and fibers): Provide 0-0.5 kcal/g, depending on hydration. Pectin, carrageenan, sugar beet fiber, beet powder, cellulose gel, locust bean gum, xanthan, guar gum, applesauce, pureed prunes, bran fiber. Brand names include Slendid, Viscarin, Sactarin, Gelcarin, Fibrex, Avicel, Novagel, Rohodigel, Uniguar, Pycol, Jaquar. Protein-based fat replacers
Provide 1.3 kcal/g or more. Not heat-stable.
Microparticulated egg white and milk protein with whey protein concentrate. Brand names include Simplesse, K Blazer, Lite, Dairy Low, Verilo. Fat-based fat replacers 1.3 kcal/g. M a y produce gastrointestinal discomfort Olestra (sucrose polyester that cannotProvides be and stool softening—a label alert is currently required in the hydrolyzed by gastrointestinal enzymes). United States. Brand name: Olean. Provides 5-9 kcaPg, depending upon fatty acid composition. Salatrim (contains fatty acids and triglycerides that are poorly absorbed). Provides 5 kcal/g. Caprenin (contains poorly absorbed fatty acids). Trailblazer (contains poorly absorbed fatty acids).
Composed of poorly absorbed fatty acids and provides between 5 and 9 kcal/g, depending on formulation.
s h o w n that individuals w h o choose these low-fat alternatives are likely to c o n s u m e less total dietary fat, although in the past few years, a slight trend toward increased dietary fat in the United States has once again been noted. During this period of low-fat food alternatives, obesity prevalence and severity have continued to rise. Often, in searching for weight loss regimens, people seek a "silver buL let"; perhaps they have viewed low-fat foods as just that, even to such an extent that other important health messages (such as those promoting high fiber and low sugar consumption, as well as increased exercise) are ignored. In addition, m a n y people tend to feel that if they are consuming low-fat foods, they can eat m o r e of them. H o w e v e r , m a n y lowfat foods have the same, and sometimes m o r e , calories than their higher-fat alternatives. Therefore, increased consumption of these products has a synergistic effect o n total energy intake. Often sugar is used in place of the fat in these products to improve palatability. Examples include low-fat cookies, muffins, and cakes. Therefore, w h U e these foods m a y be helpful in reducing overaU fat intake, they m a y not help decrease caloric consumption. A s emphasized earlier, it is the total diet that matters, not just one aspect or macronutrient. For example, just as fat replacements did not cure obesity in the 1990s, sugar replacements did not cure obesity in the 1970s and 1980s. H o w e v e r , if these foods are used in the context of a well-balanced energy-restricted diet, then they can be helpful tools for weight loss.
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SUMMARY AND CONCLUSIONS This new century marks the worst of times and the best of times for health professionals wishing to assist individuals w h o want to control their weights. The pessimists point to the present obesity epidemic ( M o k d a d et al., 1999), the considerable disease burden associated with h (Must et al., 1999), its effects on quality of life (Han, Tijhuis, Lean, & SeideU, 1998), the prohferation of unsound and ineffective diets (AUara, 2000), environmental forces that foster overconsumption and sedentary lifestyles, and the ineffectiveness of presently available weight control tools to sustain weights at healthy levels over the long run. But there are also reasons for optimism. A key positive development is that the focus of weight control efforts is changing. There is increasing stress on the need for primary prevention of weight gain and maintenance of weight loss by a combination of moderation in energy intake and increased energy output (Koplan 8>C Dietz, 1999). For those w h o are already overweight or obese, the n e w focus on achieving modest and sustained weight losses of 5 % - 1 0 % m a y provide hope ( N H L B I , 1988; U S D A & U S D H H S , 2000; WiUett, Dietz, & Colditz, 1999). The emphasis has shifted ftom the aesthetic aspects of body weight to the health aspects. Although the attainment of ideal weights associated with minimal mortahty as the goal m a y be desirable over the long run, they are unattainable for m a n y individuals, and these n e w targets are more realistic (Metropolitan Life Insurance C o m p a n y , 1983; N H L B I , 1998). The metabolic effects of different diets are also being clarified. In addition, m u c h has been learned about the prevention of weight gain and of recidivism after successful weight loss from the National Weight Control Registry (Klem, W i n g , McGuire, Seagle, & HiU, 1997). Data coUected from individuals successful at weight loss and maintenance have provided understanding of strategies that m a y be most effective. O f particular significance are behavioral and attitude adjustments, careful attention to diet, and high levels of physical activity (McGuire, Wing, Klem, & Hill, 1999). Finally, m a n y excellent books, programs, and World W i d e W e b sites are n o w avaUable to help those w h o wish to maintain or achieve healthy weights on their o w n . W e hope that health professionals using the principles and evidence-based weight control techniques discussed in this chapter will find it easier to separate the wheat from the chaff a m o n g the popular diets, and thus will be more effective in advising their patients.
ACKNOWLEDGMENTS
This material is based upon work supported by the U.S. Department of Agriculture, under Agreement No. 58-1950-9-001. Any opinions,findings,conclusions, or recommendations expressed in this publication are our o w n and do not necessarily reflect the views of the U.S. Department of Agriculture.
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diet-composition effects on energy expenditure in men. American Journal of Clinical Nutrition, 53, 4 3 0 ^ 3 6 . Saltzman, E., Dallal, G. E., Sc Roberts, S. B. (1997). The effect of high-fat and low-fat diets on voluntary energy intake and substrate oxidation: Studies in identical twins using diets matched for energy density, fiber, and palatability. American Journal of Clinical Nutrition, 66, 1332-1339. Schaefer, E. J., Lichtenstein, A. H., Lamon-Fava, S., M c N a m a r a , J. R., Schaefer, M . M., Sc Rasmussen, H. (1995). Body weight and low density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet. Journal of the American Medical Association, 274, 1450-1455. Schutz, Y., Flatt, J. P., Sc Jequier, E. (1989). Failure of dietary fat to promote fat oxidation: A factor favoring the development of obesity. American Journal of Clinical Nutrition, 50, 307-314. Schwartz, M . W., Sc Seeley, R. J. (1997). The new biology of body weight regulation. Journal of the American Dietetic Association, 97, 54-58. Sears, B., with Lawren, B. (1995). The zone: A dietary road m a p to lose weight permanently, reset your genetic code, prevent disease, achieve m a x i m u m physical performance. N e w York: HarperCollins. Shelmet, J. J., Reichard, G. A., Skutches, C. L., Hoeldtke, R. D., O w e n , O. E., Sc Boden, G. (1998). Ethanol causes acute inhibition of carbohydrate, fat, and protein oxidation and insulin resistance. Journal of Clinical Investigation, 81, 1137-1145. Shetty, P. S., Prentice, A. M., Goldberg, G. R., Murgatroyd, P. R., McKenna, A. P. M., Stubbs, R. J., Sc Volschenk, P. A. (1994). Alterations in fuel selection and voluntary food intake in response to isoenergetic manipulation of glycogen stores in humans. American Journal of Clinical Nutrition, 60, 534-543. Siggard, R., Raben, A., Sc Astrup, A. (1996). Weight loss during 12 weeks' ad libitum carbohydraterich diet in overweight and normal-weight subjects at a Danish work site. Obesity Research, 4, 347-356. Slabber, M., Barnard, H. C , Kuyl, J. M., Dannhauser, A., &: SchaU, R. (1994). Effects of a low-insulin-response, energy-restricted diet on weight loss and plasma insulin concentrations in hyperinsuhnemic obese females. American Journal of Clinical Nutrition, 60, 48-53. Smith-Schneider, L. M., Sigman-Grant, M . J., Sc Kris-Etherton, P. M . (1992). Dietary fat reduction strategies. Journal of the American Dietetic Association, 92, 34-38. Steward, H. L. (1999). Sugar busters! N e w York: Ballantine Books. Stubbs, R. J., Harbron, C. G , Murgatroyd, P. R., Sc Prentice, A. M . (1995). Covert manipulation of dietary fat and energy density: Effect on substratefluxand food intake in m e n eating ad libitum. American Journal of Clinical Nutrition, 62, 316-329. Stubbs, R. J., Murgatroyd, P. R., Goldberg, G. R., Sc Prentice, A. M . (1993). Carbohydrate balance and day-to-day regulation of food intake in humans. American Journal of Clinical Nutrition, 57, 897-903. Stunkard, A. J., Sc Messick, S. (1985). The three-factor Eating Questionnaire to measure dietary restraint, disinhibition and hunger. Journal of Psychosomatic Research, 29, 71-83. Swinburn, B., Sc Ravussin, E. (1993). Energy balance or fat balance? American Journal of Clinical Nutrition, 57(Suppl.), 766S-771S. Thomas, C. D., Peters, J. C , Reed, G. W., Si HUI, J. O. (1992). Nutrient balance and energy expenditure during ad libitum feeding of high-fat and high-carbohydrate diets in humans. American Journal of Clinical Nutrition, 55, 934-932. Tremblay, A., Plourde, G , Despres, J. P., Si Bouchard, C. (1989). Impact of dktary fat content and fat oxidation on energy intake in humans. American Journal of Clinical Nutrition, 49, 824-831. Tremblay, A., Sc St.-Pkrre, S. (1996). The hyperphagk effect of a high-fat dkt and alcohol intake persists after control for energy density. American Journal of Clinical Nutrition, 63, 479-481. Tremblay, A., Wouters, E., Wenker, M., St.-Pierre, S., Bouchard, C , Si Despres, J. P. (1995). Alcohol and a high-fat diet: A combination favoring overfeeding. American Journal of Clinical Nutrition, 62, 639-644. Ttibok, E., Si Resch, E. (1995). Intuitive eating. N e w York: St. Martin's Press. U.S. Department of Agriculture (USDA) Si U.S. Department of Health and H u m a n Servkes (USDH H S ) . (2000). Dietary guidelines for Americans. Washmgton, D C : U.S. Government Printing Office.
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Van Amelsvoort, J. M., Sc Weststrate, J. A. (1992). Amylose-amylopectin ratio in a meal affects postprandial variables in male volunteers. American Journal of Clinical Nutrition, 55, 712-718. VanltaUie, T. B. (1980). Diets for weight reduction: Mechanisms of action and physiological effects. In G. Bray (Ed.), Obesity: Comparative methods of weight control (pp. 15-24). London: John Libby. VanltaUie, T. B., 8c Yang, M . U. (1977). Current concepts in nutrition: diet and weight loss. N e w England Joumal of Medicine, 297, 1158-1160. Wadden, T. A., Sc Bartlett, S. J. (1992). Very low calorie diets: A n overview and appraisal. In T. A. Wadden Sc T. B. VanltaUie (Eds.), Treatment of the seriously obese patient (pp. 44-79). N e w York: Guiford Press Westerterp, K. R., Verboeket-van de Venne, W . P., Westerterp-Plantenga, M . S., Velthuis-te Wierik, E. J., de Graaf, C , 8c Westrate, J. A. (1996). Dietary fat and body fat: A n intervention study. International Journal of Obesity and Related Disorders, 20, 1022-1026. Westerterp-Plantenga, M . S., Si Verwegen, C. R. T. (1997). Short-term effects of an alcohol, fat, protein, or carbohydrate preload on energy intake. International Journal of Obesity, 21, S79. Westerterp-Plantenga, M . S., Si Verwegen, C. R. T. (1999). The appetizing effect of an alcohol aperitif in overweight and normal weight humans. American Journal of Clinical Nutrition, 69, 205-212. Willett, W . C , Dietz, W . H., Si Colditz, G. A. (1999). Guidelines for healthy weight. N e w England Journal of Medicine, 341(6), 4 2 7 ^ 3 4 . Wolever, T. M . S. (1999). The glycemic index: Methodology and clinical implications. Nutrition Today, 34(2), 73-77. Wolever, T. M . S., Jenkins, D. J. A., Jenkins, A. L., Si Josse, R. G. (1991). The glycemic index: methodology and clinical implications. American Journal of Clinical Nutrition, 54, 846-854. World Health Organization. (1998). Obesity: Preventing and managing the global epidemic (Publication N o . W H O / N U T / N C D / 9 8 . 1 ) . Geneva: Author. Zurlo, F., Lillioja, S., Esposito-Del Puente, A., N y o m b a , B. L., Raz, I., Saad, M., Swinburn, B., Knowler, W . C , Bogardus, C , Si Ravussin, E. (1990). L o w ration of fat to carbohydrate oxidation as a predictor of weight gain: A study of 24-h R Q . American Journal of Physiology, 259, E650-E657.
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APPENDIX 12.1. PHYSIOLOGICAL BASIS OF WEIGHT LOSS
Human beings consume and expend energy from the metabolic fuels—protein, carbohydrate fat—and some consume alcohol as well. Each of these fuels is metabolized, stored, and regulated in different ways within the body (Table 12.4). Thus it is relevant to consider overall energy balance as the s u m of the balances of the various energy-providing substrates. The different metabolic fates of the macronutrients have implications in the overall regulation of energy balance.
Protein Protein provides a net of 4 kcal/g. In most h u m a n diets, protein provides the least amount of food energy, with the least vanabUity—usually 1 0 % - 1 5 % of total kilocalories consumed. In the body, protein is not stored as a fuel reserve, and there is no protein storage depot. M o s t protein is used to synthesize the body's structural and functional proteins, and the remainder of that consumed is preferentially oxidized. Thus protein metabolism and protein balance are both highly regulated (Abbott et al., 1988). Protein stores in muscle or elsewhere do not increase in response to increases in protein intake alone. Stimuli such as growth factors, androgens, physical training, and weight gain, as well as diet, are required for a positive protein balance to occur.
Carbohydrate Carbohydrate and fat are both stored in the body. The amount of dietary carbohydrate normally consumed per day (about 200-300 g, about 4 kcal/g) consthutes between 5 0 % and 7 5 % of food energy in most h u m a n dietary patterns. The amount of carbohydrate consumed is relatively high, compared to the limited capacity of the h u m a n body to store it as glycogen in the liver and skeletal muscle (150-500 g). The central nervous system, along with other vital tissues, relies exclusively on carbohydrate (as glucose) for fuel. Carbohydrate metabolism is highly regulated by the hormones insulin and glucagon, and others. Glycogen stores, particularly those in the liver, can fluctuate markedly even within the course of a day as carbohydrate is ingested and oxidized for energy. It has been suggested that glycogen stores help to regulate food intake through negative feedback, although a significant ef-
T A B L E 12.4. Macronutrient Storage in H u m a n s Protein Energy content (kcal/g) Storage Relative size of stores Daily variability in stores Potential for expansion Does intake of nutrient stimulate its oxidation?
Fat
Carbohydrate
Alcohol
~4
4
9
7
Lean tissue, not for storage Moderate
Glycogen
Adipose
None
Small
—
Small
Large
Large (most humans) Small
Moderate
Small
Large
—
Yes
Yes
No
Yes
—
Note. From Swinburn and Ravussin (1993). Copyright 1993 by the American Society for CUnical Nutrition. Adapted by permission.
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feet of this mechanism has not been demonstrated in humans (Stubbs et al., 1995). Despite its rapid turnover, effective autoregulation of carbohydrate balance is maintained over wide ranges of carbohydrate intake, through adjustments in carbohydrate oxidation (HUI et al, 1991; Shetty et al., 1994; Stubbs, Murgatroyd, Goldberg, Sc Prentice, 1993). In general, carbohydrate oxidation tends to increase readily with increasing carbohydrate intake, whereas oxidation of fat does not do so (Flatt, Ravussin, Acheson, Sc Jequier, 1985; Schutz, Flatt, Sc Jequier, 1989). O n normal mixed diets, most ingested carbohydrate that is not stored as glycogen is oxidized and not converted into fat. Massive carbohydrate overfeeding (-88% of energy over several days), resulting in m a x i m u m glycogen stores, is required before net synthesis of fat from carbohydrate ("de novo lipogenesis") will occur in normal humans (Acheson et al., 1988). Excess dietary carbohydrate consumption during positive energy balance can lead to positive fat balance, owing to its sparing effect on fat oxidation (Horton et al., 1995).
Fat Fat Storage and Oxidation Dietary fat provides 9 kcal/g and generally constitutes anywhere from 15% to 50% of calories in human diets. In contrast to carbohydrate, the storage capacity of fat within the body is virtually limitless, and it is not tightly regulated. Thus excess overall food energy intake tends to result in most of the excess energy's being stored directly from dietary fat (Flatt, 1988; Swinburn Sc Ravussin, 1993). Fat stores have not been shown to regulate energy intake, although newly emerging data on leptin's effects m a y provide some evidence in the future (Schwartz Sc Seeley, 1997). Fat oxidation does not readily adjust to dietary fat intake, because it is inversely related to carbohydrate oxidation for a given level of energy expenditure with normal activities. This is related to the fact that carbohydrate balance is more closely regulated than fat balance in humans (Abbott et al., 1988; Flatt et al., 1985). It is possible that differences in the responsiveness of fat oxidation to intake occur between individuals (Thomas, Peters, Reed, Sc HiU, 1992). O n e factor that m a y improve this responsiveness of fat oxidahon to fat intake is physical fitness, as evidenced by aerobic capacity (Melanson, Saltzman, Russell, Sc Roberts, 1997). However, fat oxidation usually responds less readily to changes in fat intake than carbohydrate oxidation responds to changes in carbohydrate intake.
De Novo Lipogenesis De novo lipogenesis (synthesis of fat from carbohydrate) does not occur on normal mixed diets (Acheson et al., 1988). O n typical mixed diets, protein and carbohydrate will first be oxidized for energy, followed by fat, and if an overall excess of energy is ingested, dietary fat will be the fuel that is stored. For example, if an individual w h o is in energy balance w h e n consuming 2,400 kcal/day of a normal mixed diet starts to consume an additional 400 kcal/day exclusively from carbohydrate, the metabolic fate of this excess carbohydrate will be glycogen storage and perhaps oxidization. The excess dietary energy will be stored directly from dietary fat, rather than from the process of dietary carbohydrate's being converted to body fat. This is the most energetically efficient form of energy storage, since minimal conversion between macronutrients (carbohydrate to fat) is required. D e novo lipogenesis is a very inefficient means of energy storage. If it were to occur more routinely in humans, m u c h more energy would be wasted (i.e., - 2 4 % ) in the process of converting carbohydrate to body fat. Overfeeding studies have substantiated this; more energy is stored w h e n the excess comes from fat than w h e n h comes from carbohydrate (Horton et al, 1995). During underfeeding, the effects of altering energy from fat are less dramatic than during overfeeding (Golay et al., 1996; Rumpler, Seak, Miles, Sc Bodwell, 1991). The hypocaloric state is influenced by the ratio of fat to carbohydrate, because even though the metabolic costs of mobilizing fat in adipose tissue are similar for each, tissues such as the brain have an obligatory requirement for carbohydrate; and if car-
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bohydrate is not available from the diet, skeletal muscle and other body protein must be metabolized to provide it. In studies of free-living humans ranging from 11 weeks to 1 year in duration, fat restriction in the absence of other dietary changes produced only modest body weight losses of about 1-3 kg (Boyar et al., 1988; Raben et al., 1995; Siggard, Raben, 6c Astrup, 1996). As discussed later, this m a y be related to the fact that overall energy deficit is more important in the hypocaloric state than is macronutrient composhion. S o m e data suggest that energy balance is more strongly defended during energy deprivation than it is during energy surplus, impeding weight loss to a greater extent than weight gain (Blundell, 1991; Caputo Sc Mattes, 1992; Saltzman et al., 1997). In part, these effects m a y be due to alterations in resting metabolism and nonobligatory physical activity.
Alcohol Alcohol (ethanol), though not an essential nutrient, is another source of metabolizable energy for m a n y individuals. With approximately 7 kcal/g, alcohol provides more energy per unit of weight than carbohydrate or protein (each -4 kcal/g), but less than fat (-9 kcal/g). Since the body has no storage capacity for alcohol, any ingested alcohol is oxidized immediately; the rate at which this occurs will depend on the individual's rate of energy expenditure (Lands, 1995). Excess alcohol awaiting oxidation circulates in the blood and m a y reach toxic levels, with effects on both physical and mental performance. Therefore, in normal individuals, chronically positive alcohol balance does not occur. It is just positive transiently upon ingestion, and alcohol oxidation eventually becomes equal to alcohol intake. If protein, carbohydrate, and/or fat are consumed at the same time as alcohol is ingested, their oxidation will be suppressed (most notably fat oxidation), since alcohol is preferentially oxidized, and the other macronutrients will be stored (Shelmet et al., 1988). Therefore, consumption of alcohol can lead to a positive fat balance through the sparing effect of alcohol on fat oxidation, leading to increased fat storage. Chronic overconsumption of alcohol can thus lead to fatty liver and dyslipidemia. Another important consideration for alcohol's influence on energy balance is its effects on energy intake. Alcohol is positioned at the bottom of the hierarchy of satiating efficiency of metabolic fuels consumed by humans. Generally, it is accepted that the fuels satiate from lowest to highest: alcohol, fat, carbohydrate (depending on type), and protein (Westerterp-Plantenga Sc Verwegen, 1997). Alcohol energy is additive to the diet, producing no compensation in energy intake under most ad libitum situations, and in fact it m a y stimulate appetite (Poppit, Eckhardt, McGonagle, Murgatroyd, & Prentice, 1996; Tremblay et al., 1995). In nonalcoholic individuals, alcohol (as beer or wine) stimulates appetite and food intake to a greater extent than the other metabolic fuels do (Mattes, 1996; Westerterp-Plantenga Sc Verwegen, 1997, 1999). This appetite-stimulating effect of alcohol is probably dose-dependent within usual levels of alcohol intakes (Mattes, 1996). Alcohol consumption has been associated with higher eating rates, prolonged meal durations, delayed increases in satiation during a meal, and prolonged eating after satiation has reached its m a x i m u m in nonalcoholic individuals (Westerterp-Plantenga & Verwegen, 1999). W h e n alcohol is combined with high fat consumption, these two fuels act synergistically to produce a hyperphagic response (Tremblay et al., 1995), which is independent of the energy density of the fuels (Tremblay 8i St.-Pkrre, 1996). For these reasons, alcohol consumption is usually contraindicated in weight loss diets. Macronutrient Balance Just as a dynamic equation is more appropriate for expressing energy balance than is a static one in humans, so too are d y n a m k equations appropriate for expressing macronutrient balances. For example, as an individual accumulates body fat (from a positive fat balance), the rate of fatty acid turnover increases, and thus fat oxidation increases until it becomes commensurate with fat intake. A new fat balance is achieved at this new higher level until it is perturbed again. Fat stored in adipocytes can
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only significantly be depleted through oxidation, by using it as a metabolic fuel. Increased fat oxidation from exercise and/or decreased fat (or energy) intake from the diet will result in negative fat balance. A positive fat balance results from decreases in oxidation, perhaps from more sedentary behavior and/or further increases in dietary fat (or energy). Overweight and obesity are thus actually conditions of chronically positive fat balance—that is, greater fat retention than oxidation. Macronutrient balances and imbalances are expressed as the match, or mismatch, of the "food quotient" (ratio of dietary carbohydrate to fat) and the "respiratory quotient" (ratio of carbohydrate to fat oxidation). During periods of stability in body weight and composition, the respiratory quotient reflects the food quotient (Flatt, 1995). W h e n an individual is gaining body fat, the respiratory quotient is higher than the food quotient (reflecting lower fat oxidation than intake). As a person loses fat, the respiratory quotient is lower than the food quotient (reflecting higher fat oxidation than intake). In prospective studies, a high 24-hour respiratory quotient (low ratio of fat to carbohydrate oxidation) has been found to be predictive of weight gain over 6-15 months (Froidevaux, Schutz, Christin, Si Jequier, 1993) and up to 3 years (Zurlo et al., 1990). The corollary to these metabolic considerations is that a high-fat, low-carbohydrate ad libitum diet should cause weight gain and a low-fat, high-carbohydrate ad libitum diet should cause weight loss, all other factors being equal. This is supported by population studies (Lissner Si Heitmann, 1995) and by food intake studies showing that fat intake tends to be positively correlated with body fatness (Dreon et al., 1988; Prentice Sc Poppit, 1996; Tremblay, Plourde, Despres, Sc Bouchard, 1989; Westerterp et al., 1996). In clinical studies of free-living individuals, switches from a high- to a low-fat diet have been shown to result in weight loss, at least in thefirstfew months (Kendall et al., 1991; Schaefer et al., 1995). Whether eventual adjustments occur with chronic feeding of such low-fat regimens is not so clear, however. Increases in energy expenditure with overfeeding of fat are not as high as if the overfeeding is in the form of carbohydrate (Horton et al., 1995). O n the other hand, at weight maintenance or on hypocaloric intakes, changes in energy expenditure m a y not be significantly different between high-fat and low-fat diets (Hill et al., 1991). Data showing that high-fat diets are associated with overweight and obesity (Miller, Lindeman, Wallace, Sc Niederpruem, 1990; Tremblay et al., 1989) support the hypothesis that both high-energy and high-fat intakes are involved in the etiology of obesity. As mentioned above, carbohydrate balance is more tightly regulated than fat balance, and fat balance m a y be chronically positive over years. The combination of these data and others has led some to equate fat balance with energy balance (Swinburn Si Ravussin, 1993), and to recommend counting fat grams instead of kilocalories in weight reduction and maintenance regimens (Smith-Schneider, Sigman-Grant, Si Kris-Etherton, 1992). Although fat gram counting m a y be appropriate for some individuals, this strategy has not proven effective for aU obese persons in their efforts to lose weight. Over the 1980s, overall fat intake in the United States reportedly decreased, while the prevalence of obesity continued to rise (Ernst, Sempos, Briefel, Si Clark, 1997; Kuczmarski, Flegal, Si Campbell, 1994). Thus the usefulness of low-fat diets in preventing obesity, in the absence of control over energy intake, is questionable (Ludwig et al., 1999; Willett et al., 1999). Moreover, the causation of the increase in obesity is not well established; it m a y also be due to declines in energy expenditure. Another explanation of the lack of effect of fat reduction on overweight m a y be underreporting of fat intakes, which is k n o w n to be c o m m o n (Heymsfield et al., 1995). It is also highly likely that energy intakes have increased even in the presence of reduced fat intake, due to increased dietary carbohydrate intake (and perhaps, in some individuals, increased alcohol intake). If excess energy is taken in and not oxidized, h must be stored. Probably, in m a n y individuals over the long term, energy intake compensation does occur. Therefore, even on a low-fat, high-carbohydrate diet, excess energy intake m a y result with consequent increases in energy storage preferentially from the remaining dietary fat and excessive accumulation of adiposetissue.However, this needs to be demonstrated experimentally, and the question of the long-term effectiveness of dietary fat reduction in prevention of weight gain and stimulation of weight loss needs to be considered.
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Diet Composition for Weight Loss Differences in dietary composition may be of more importance in the causation of obesity than they are in the composition of diets for weight loss. In the hypocaloric state, fat stores are mobilized and the metabolic fuel mix is high in fat, regardless of dietary composition. That is, assuming that the reducing diet is high enough in protein to meet the body's needs for essential amino acids, and high enough in carbohydrate (approximately 100 g) to meet needs to maintain blood sugar levels, variations in fat, protein, and carbohydrate have relatively little effects on the composition of the fuels that are metabolized. This fact has eluded most writers of popular diet books; as a result, endless variations on the reducing diet theme are constantly being promulgated. From the practical standpoint, therefore, the composition of the reducing diet plays a relatively minor role compared to the energy level of the reducing diet. The means for reducing body fatness are straightforward: Either energy intake is decreased, energy output is increased, or both are altered simultaneously to produce a net energy deficit. If such a deficit persists for long enough, body fat and weight are lost in a linear manner. The slope of the decline is determined by the size of the energy deficit. Moreover, the loss of fat is directly proportional to the size and duration of the energy deficit. O f course, the rate of weight loss depends on the extent to which the individual adheres to the weight loss regimen, and also onfluidshifts. Over the short term, such as a few weeks, deviations from this linear relationship between energetic deficit and weight loss often occur. This is mostly because weight loss also reflects shifts in glycogen stores and water balance, especially in the first few weeks on a reducing diet. Such alterations are most pronounced early in weight loss, but they m a y also occur at other points, depending on adherence and shifts in body water with changes in the energy-providing nutrients that are consumed. Since 3 g of water are associated with each gram of stored glycogen in the body, daily shifts in glycogen stores will be reflected by shifts in body weight three times as large (Flatt, 1995). The size of the energy deficit, the composition of the reducing diet, and the type and amount of concomitant physical activity can alter the mix of metabolic fuels that is burned for energy, the type of tissue that is lost, fluid and electrolyte balance, and weight loss. For example, w h e n dietary energy is too restrictive, a greater percentage of body weight is lost as lean tissue (Davies et al., 1989; Elliot, Goldberg, Kuehl, Sc Bennett, 1989; Leibel, Rosenbaum, Sc Hirsch, 1995), whereas w h e n exercise is incorporated into the weight loss strategy, less lean tissue m a y be lost (Marks et al., 1995). Ultimate success in achieving and maintaining a leaner physique depends on sustaining somewhat lower levels of energy intake and higher levels of energy output compared to those prior to weight reduction. This is so because as adipose tissue is lost, some actively metabolizing lean tissue is also lost, thus decreasing R M R (EUiot et al., 1989; Leibel et al., 1995). Moreover, less energy is required to move the lighter body, further decreasing energy output (Froidevaux et al., 1993). Both the dynamic energy balance equation and separate macronutrient balance equations are valid; they are not mutually exclusive. The dynamic energy balance can be seen as the summation of the dynamic macronutrient balance equations (Abbott et al, 1988). Energy will not be stored during a negative energy balance, and net energy liberation from stores will not occur during positive energy balance. Overall energy intake matters, and so does the source of nutrients. O n a typical mixed diet, energy from carbohydrate will not be converted to fat, but it will be either stored as more labile glycogen or oxidized, and excess energy will be stored from exogenous fat, with a concomitant decrease in fat oxidation. In other words, a kilocalorie is still a kilocalorie, but the different metabolism of the individual macronutrients has implications in the regulation of this overall energy balance, with possible effects on both energy expenditure and intake regulation. In order for the concept of macronutrient balances to support a recommendation of avoiding dietary fat to cause weight loss, glycogen stores would have to provide negative feedback regulation on ad libitum energy intake. This phenomenon has been adequately demonstrated experimentally in animal but not h u m a n models. However, the converse, weight gain, m a y be different. Present evidence
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suggests that if individuals eat to maintain adequate carbohydrate stores, then a high-fat, low-carbohydrate diet will render them susceptible to overconsumption of energy. This theory is m u c h easier to prove in laboratory animals than in humans, because h u m a n food intake is influenced by a complex array of factors, including emotional, cognitive, psychological, and social influences, as well as meal palatability (de Castro Sc de Castro, 1989; Melanson, Westerterp-Plantenga, Campfield, Sc Saris, 1999; Rolls, R o w e , Si RoUs, 1982; Stunkard Si Messick, 1985). If glycogen stores do in fact regulate energy intake in humans, then the individuals for w h o m fat avoidance is effective will be those w h o eat solely in response to physiological hunger signals rather than in response to external cues. Such rare individuals probably exist, but they are few in number, especially a m o n g those w h o seek to reduce body weight. Energy Density Energy density of the different macronutrients, and thus of different foods, also has implications that must be considered in assessing the relative importance of focusing on kilocalories versus fat in giving dieters advice. As noted earlier, protein and carbohydrate each provide approximately 4 kcal/g, whereas fat contains 9 kcal/g, and alcohol 7 kcal/g. By counting fat grams, individuals can account for over twice as m u c h energy intake per gram than they could by counting protein or carbohydrate grams. Therefore, the fat-gram-counting strategy m a y be effective for some individuals (Smith-Schneider et al., 1992). Furthermore, experimental data support the concept that energetically dense foods and diets are more easUy overconsumed (Rolls Si H a m m e r , 1995; Saltzman et al., 1997; Stubbs et al., 1995). Since fat-rich foods tend to be highly palatable and energy-dense, m u c h energy can be consumed from these foods in a short period of time (Bell, Castellanos, Pelkman, Thorwart, Si Rolls, 1998; Rolls Si Shide, 1992). Therefore, avoiding fat, the most energy-dense macronutrient, m a y help some patients both in reducing ad libitum food intake and in consciously controlling their intakes. Ingesting low-fat, low-energy-density diets that are high in complex carbohydrate and fiber can lead to lower ad libitum food intake and weight loss (Schaefer et al., 1995). If one is eating to a point of gastric fullness, then the energy content of the digesta in the stomach should be less w h e n it is full of carbohydrate (especially if this is also high-fiber) than w h e n it is full of fat. For example, it would be much more difficult to consume 1,000 kcal in the form of lettuce than in the form of whipped cream. Some investigators assert that individuals eat according to weight or volume rather than energy (KendaU et al., 1991; Lissner et al., 1987; Saltzman et al., 1997; Stubbs et al., 1995). If this is true, a diet with a low energy density (low in fat, high in complex carbohydrate) should lead to lower spontaneous intake than a high-energy-density diet (high in fat, low in complex carbohydrate). At present, the data are lacking to determine whether this is true or not, especially over the longer term. As an individual reduces the amount of energy consumed relative to expenditure, a negative energy balance is created, and gradual shifts in metabolism occur. Reductions in the availability of endogenous fuels lead to a decline in the insulin-to-glucagon ratio, with concomitant decreases in anabolism and increases in catabolism. Glycogen is mobilized from the liver, making glucose available to tissues throughout the body, particularly the central nervous system. Within muscles, glycogenolysis liberates glucose for fuel contractions and other intracellular processes. As glycogen stores decline, lipolysis within adipose tissue will gradually rise, making unesterified fatty acids available as an additional fuel source for non-glucose-dependent tissues in the body. Gradually, the body shifts from a carbohydrate-based to a fat- and protein-based fuel economy. If glucose availability continues to decrease, gluconeogenesis commences, whereby amino acids are degraded, the carbon skeletons are utilized to construct glucose, and the nitrogenous wastes are excreted in the urine. Fat cannot be converted to carbohydrate, because its catabolism (P oxidation) yields two-carbon units that cannot enter the gluconeogenic pathway. O n a weight loss diet, fatty acids within the adipose tissue are liberated and oxidized for energy, decreasing body fat mass. The extent of lean body mass loss will depend on various factors. In general, if an energy deficit persists for long enough, and other nutrients are pro-
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vided in adequate amounts, body fat and weight are lost in a more or less linear manner. However, early and/or rapid weight loss m a y largely be the result of glycogen depletion and water balance shifts. Since glycogen stores in the liver and in muscles amount to approximately 500 g in the average person (about 2,000 kcal), one would expect that this would not be very noticeable. However, since each gram of glycogen holds with it 3 g of water, 0.5 kg of glycogen oxidization m a y be reflected on the scale as a total weight loss of 2 kg. The reverse holds true if glycogen is synthesized; rapid gains in weight far in excess of calories consumed often occur on refeeding of a glycogen-depleted individual due to such shifts. Body fat contains about 3,500 kcal/pound (454 g adipose tissue x 9 kcal/g x correction factor for glycerol and adipocyte structural proteins). Thus a negative energy balance of 3,500 kcal is required for each pound of adipose tissue loss. About 1 pound would be lost per week with a daily deficit of 500 kcal (500 kcal x 7 days), and a negative energy balance of 1,000 kcal/day would result in 2 pounds of body fat loss. Weight losses of more than 0.5 to 1 pound per week are not suggested for self-initiated efforts. Even under medical supervision, a loss of no more than 2 pounds per week is usually recommended. W h e n weight losses are more rapid than this, risks of excessive loss of lean body mass increase, as do the risks of nutrient deficiencies, fatigue, and increases in other side effects (discussed in the chapter text). Furthermore, weight loss that occurs rapidly m a y be more difficult to maintain than gradual weight loss.
1
Exercise
a n d
3
W e i g h t
M a n a g e m e n t
S T E V E N N . BLAIR ELIZABETH A. LEERMAKERS
Much attention has recently been paid to overweight and obesity as public health problems (National Heart, Lung, and Blood Institute [NHLBI], 1998; World Health Organization, 1998). It is clear that the prevalence of overweight and obesity is increasing in many countries around the world, and that the rate of increase may be especially rapid. The prevalence of obesity (body mass index [BMI] > 30.0 kg/m^) in the United States during 1990 to 1998 increased from 1 2 % to 1 8 % in adults—a remarkable increase of 5 0 % in just 8 years (Mokdad et al., 1999). There was a comparable increase in w o m e n and men, and increases occurred in all demographic groups. Concern about this rapid increase has generated a call to action for changes in public health policy (Koplan & Dietz, 1999). W e agree that there has been an increase in the prevalence of overweight and obesity in the past few years, and that this represents an important public health problem. However, we are concerned that there is too much emphasis placed solely on markers of obesity such as B M I and diet, with too little attention given to other important issues, such as physical inactivity. In this chapter, we first address issues related to the possible causes of the increasing prevalence of overweight and obesity in the United States and other countries. W e then review the effects of physical activity on weight loss and weight loss maintenance, followed by a discussion of the current consensus public health recommendation for physical activity. Next, we discuss various approaches to physical activity interventions, with an emphasis on lifestyle physical activity. The last major section includes a review of the interrelationships among obesity, physical activity, and health outcomes. This is followed by a summary and conclusion.
CAUSES OF THE INCREASE IN THE PREVALENCE O F O V E R W E I G H T A N D OBESITY
Most experts and recent guidelines acknowledge a role for physical activity in the et and treatment of overweight and obesity (Bouchard & Blah, 1999a, 1999b; Bouchard, De283
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spres, & Tremblay, 1993; World Health Organization, 1998). We do not have adequate data to describe with confidence the specific cause(s) of the recent increase in the prevalence of overweight and obesity in the United States and other countries. Clearly, obesity is inevitably due to a positive energy balance over time, which leads to the accumulation of excess weight. Data from dietary surveys in the United States s h o w either a stable or perhaps a slight increase in average daily caloric intake, depending on the survey (Centers for Disease Control and Prevention, 1994). W e have no data from representative population samples on energy expenditure or on the change in energy expenditure over recent years. There are data on participation in various physical activities, but they are totally inadequate to estimate total energy expenditure. Current data on physical activity levels in representative samples of the U.S. population are from various surveys conducted by the National Center for Health Statistics and the Centers for Disease Control and Prevention, and have been summarized in Physical Activity and Health: A Report of the Surgeon General (U.S. Department of Health and H u m a n Services, 1996). These data s h o w little change in recent years in the proportion of the aduh population that participates regularly in physical activity or in the proportion that is sedentary. This could lead to the conclusion that total energy expenditure has remained constant. W e believe that this is unlikely. W e think that the environment has become increasingly toxic for physical activity, as indicated by the growing popularity of sedentary pursuits such as surfing the Internet and playing computer games. Added to these sedentary leisure activities is the ubiquitous use of electrical power to perform tasks previously done by h u m a n energy expenditure. Electric doors are widely prevalent; stairs are hard to find in m a n y public buildings (or, if found, are frequently unavailable for use other than for fire emergencies); moving sidewalks transport us in airports; and labor-saving devices abound at h o m e and at the workplace. Data to support our opinions concerning changes in h u m a n energy expenditure are not available. W h a t is discouraging is that there has been virtually no attempt to obtain such data on representative population samples. Although w e do not have access to detailed figures, surely no one can doubt that the U.S. Public Health Service (USPHS) and U.S. Department of Agriculture ( U S D A ) have spent far more m o n e y developing tools to assess energy intake than on developing and validating tools to assess energy expenditure and on applying these tools to representative population samples. Emphasis on Dietary Assessnnent The USPHS and USDA have conducted numerous national surveys of dietary intake over the past several decades. Although these surveys provide estimates of per capita daily caloric intake, m a n y experts have stated in private conversations that the data on energy intake are highly suspect, if not completely useless. W e have not found such harsh statements in print from these experts, but there are pubhshed criticisms of dietary assessment methodology. For example, underreporting of dietary intake is apparently widespread (Briefel, Sempos, M c D o w e U , Chien, & Alaimo, 1997). O n e hypothesis, for which there is only anecdotal evidence, is that as concern about underreporting grows, those conducting dietary surveys engage in more intensive probing to elicit a more complete record of food consumption. This could lead to spurious increases in reported caloric intake. Whether or not this speculation is correct, current data do not allow for firm conclusions regarding changes in average daily caloric intake over the past several years. The prevailing opinion appears to be that the recent increase in the prevalence of overweight and obesity is due primarily to increases in caloric consumption over time. Various explanations have been proposed, such as the increases in the number of meals eaten away
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from home, in the number of meals eaten at (or taken away from) fast-food restaurants, in the size of plates and portion sizes, and in the consumption of convenience foods and foods with "empty calories." Despite such claims, data from the major national dietary surveys s h o w little or no increase in average daily caloric intake by individuals. W e think that the persistent emphasis on trying to assess dietary factors and energy intake, with no attempt to obtain valid estimates of energy expenditure, leads u s — a s clinicians, scientists, and public health professionals—down the wrong path. W e have a few simple questions. If the data on caloric intake from national surveys are invalid for the determination of per capita daily caloric intake, w h y do w e continue to use the same methodology and spend millions of dollars collecting these data? H a s there been an overemphasis on diet and caloric intake as determinants of overweight and obesity? Are w e going to continue with the policy of not collecting data on energy expenditure in national surveys? W i U w e (both health professionals and the general public) continue to focus primarily on diet as the cause and treatment of overweight and obesity?
Increased Attention to Physical Activity Although attention to physical activity in the prevention and treatment of obesity has increased somewhat in the past few years, it clearly receives less attention than diet does (Levy, 1993). A s an example, the appendix of the N H L B I (1998) report on obesity contains 23 pages of material on food shopping lists, tips on food preparation and eating out, instruction in reading food labels, and low-calorie meal plans. In stark contrast, there is no information in the appendix on h o w to increase physical activity. W e m a y be biased, but w e do not think that there is a national shortage of low-calorie m e n u plans. Every supermarket checkout counter has several publications that contain such plans and advice on dieting, and books touting special diets and eating plans are perennial fixtures on lists of best-selling books. In our opinion, our nation has had a large, naturalistic experiment on the use of lowcalorie and low-fat diets for weight management. The results are clear: This approach has been a near-complete failure, as evidenced by the recent rapid increase in the prevalence of overweight and obesity ( M o k d a d et al., 1999). W e hken the strategies for weight control to the strategies for dealing with the drug problem in our society (Drucker, 1999). Both appear to be dismal failures, and n e w strategies need to be developed and tested. Obviously, w e favor developing, implementing, and testing a strategy of coordinated and comprehensive programs to increase levels of physical activity in the population.
R E L A T I O N S H I P B E T W E E N P H Y S I C A L ACTIVITY A N D W E I G H T C H A N G E Williamson and colleagues (1993) examined the association between physical activity level and the 10-year change in body weight in 3,515 m e n and 5,810 w o m e n aged 25-74 years. At basehne and 10-year foUow-up, participants indicated whether their level of recreational and nonrecreational physical activity was of low, moderate, or high intensity. Participants' weights were measured at baseline and follow-up. The investigators found no relationship between baseline activity levels and subsequent weight change in w o m e n or m e n . However, m e n whose activity levels were low at baseline and remained low at follow-up, and those with decreases in activity level from baseline to follow-up, gained 1.3 kg and 1.4 kg more, respectively, than m e n whose activity levels were high at both assessments. W o m e n whose activity was low at both measurements, and those with decreases in activity from baseline to follow-
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up, gained 2.1 kg and 1.9 kg more, respectively, than women whose activity levels were high at both measurements. The relative risk of major weight gain (>13 kg) for people whose activity level was low at both the baseline and follow-up interviews was 2.3 times higher in men and 7.1 times higher in w o m e n than in individuals whose activity level was high at baseline and follow-up. These results suggest that individuals w h o maintain a consistently high level of physical activity experience less weight gain than people w h o do not exercise regularly. French and colleagues (1994) examined predictors of weight change over a 2-year period in 1,639 male and 1,913 female employees from area worksites. Body weight was measured at baseline and 2-year follow-up. Physical activity was estimated with a 13-item exercise frequency recall. Participants indicated h o w often they participated in leisure-time and occupational physical activities of varying intensity. Analyses were conducted on the average weekly frequency of physical activity in each of four categories: (1) high-intensity activities; (2) moderate-intensity activities; (3) group and racquet sports; and (4) occupational activity. Increases in physical activity from baseline to follow-up were associated with weight losses. A m o n g w o m e n , an increase of one walking session per week w a s associated with a decrease in body weight of 0.79 kg, and an increase of one high-intensity training session per week was associated with a decrease in body weight of 0.63 kg, over the 2-year period. For m e n , an increase of one walking session per week or one high-intensity activity was associated with a decrease of 0.39 or 1.59 kg, respectively, over the 2-year period. Regular physical activity m a y delay or prevent the weight gain that often accompanies aging. W e (DiPietro, Kohl, Barlow, & Blah, 1997) foUowed 4,599 m e n and 724 w o m e n w h o received three examinations at the Cooper Clinic in Dallas, Texas, during the interval 1970 to 1994. This study assessed weight and physical activity or fitness at three time points, allowing us to examine changes in fitness from the first to the second examination as a predictor of weight gain by the third examination. At each examination, weight, cardiorespiratory fitness (determined by a maximal exercise test on a treadmill), and other clinical variables were measured. The interval between the first and second examinations averaged 1.8 years, and the total observation period from the first to the third examination was about 7.5 years. Results showed that each 1-minute improvement in treadmill time from the first to the second examination was associated with a 9 % decrease in the odds of a 5-kg weight gain for w o m e n and a 1 4 % decrease for men. There were even stronger reduced odds (21%) of a 10-kg weight gain in both w o m e n and m e n with each additional minute on the treadmill test. These data suggest that a fit and active w a y of life prevents weight gain. Physical Activity and Weight Loss Physical activity alone produces only modest weight loss. A meta-analysis of weight loss studies found that 21-week aerobic exercise programs produce weight losses of 2.9 kg, compared with losses of 11 kg from 15-week programs of caloric restriction (Miller, Koceja, & Hamilton, 1997). Adding 30-60 minutes of physical activity, three times a week, to a caloric restriction program increases the amount of weight lost by approximately 2 kg (NHLBI, 1998). It is very difficult for people to lose large amounts of weight, or at least to lose weight quickly, by exercise alone. A general guideline is that a pound of body fat yields about 3,500 kilocalories (kcal) w h e n oxidized. Given that a 75-kg person burns approximately 100 kcal by walking 1 mile, one would have to walk about 35 miles to expend the energy contained in 1 pound of fat. For individuals w h o m a y be 50 or 100 pounds overweight, losing that m u c h weight by exercise alone is a formidable challenge. Furthermore, given that m a n y overweight or obese individuals are quhe sedentary and unfit, they cannot perform
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large amounts of exercise, at least over the short term. Thus they do not have the capacity to expend large amounts of energy.
Physical Activity and Maintenance of Weight Loss
Even though physical activity is not the most efficient method of losing weight, it appears to be crucial for maintaining weight loss. O n e study examined self-reported activity levels of obese w o m e n w h o regained weight after successful weight loss ("relapsers"), formerly obese w o m e n w h o maintained their weight loss ("maintainers"), and normal-weight w o m e n w h o maintained their weight (controls) (Kayman, Bruvold, & Stern, 1990). Regular physical activity (at least three times a week for > 30 minutes) was reported by 9 0 % of the maintainers and 8 2 % of the controls, but by only 3 4 % of the relapsers. These results suggest the importance of physical activity in maintaining weight, both a m o n g normal-weight individuals and formerly obese individuals w h o have lost weight. The National Weight Control Registry, a group of 1,047 w o m e n and m e n w h o lost at least 30 pounds (13.6 kg) and maintained that loss for at least 1 year, provides even stronger support for the importance of physical activity in maintaining weight loss (McGuire, Wing, Klem, Seagle, & HUI, 1998). The average weight loss in this group was 64 pounds (29.0 kg) over an average 6.9 years of follow-up. Successful weight maintainers averaged 1 hour or more of moderate to vigorous intensity physical activity per day. Schoeller and colleagues (1986), w h o determined energy expenditure objectively by the doubly labele4 water technique, found similarly high levels of physical activity a m o n g successful weight loss maintainers. Maintainers had an average daily energy expenditure of 1.9 metabolic equivalents, which requires about 80 minutes of moderate-intensity physical activity or 35 minutes of vigorous activity per day. Although the immediate effects of exercise are limited, the long-term cumulative effect of smaU changes in activity level can be beneficial. For example, if a 100-pound person played golf only 2 hours per outing (an additional 350 kcal per outing), for 2 days a week (700 kcal), it would take about 5 weeks, or 10 golfing days, to lose 0.45 kg (1 pound) of fat (3,500 kcal). If the person played golf year-round, golfing 2 days per week (hypothetically) would produce a 4.5-kg loss of fat during the year, provided that food intake remained fairly constant (Katch & McArdle, 1993). W e speculate, based on the epidemiological studies reviewed above, that an individual w h o is regularly active throughout his or her lifetime would be approximately 13.6 kg (30 pounds) lighter by age 65 than someone w h o had a consistently sedentary lifestyle over this period. Jeffery and French (1997) found that m e n and w o m e n 20-45 years of age gained an average of 1.9 pounds and 1.4 pounds, respectively, in 1 year. If w e assume that people gain 50 pounds over 4 0 years, h o w m u c h physical activity would it take to counteract the increased caloric intake? Assuming that people w h o gain 1-1.5 pounds per year consume an extra 10-15 kcal per day, it would not require very m u c h physical activity to burn those extra kilocalories. For example, a 75-kg person would burn 15 kcal by walking for 2.5 minutes. Physical activity, then, m a y play a very important role in long-term weight regulation. (For more information on exercise and weight maintenance, see Wing, Chapter 14, and Perri & Corsica, Chapter 17, this volume.)
PUBLIC HEALTH RECOMMENDATIONS FOR PHYSICAL ACTIVITY
It is clear that a sedentary and unfit way of life increases risk of several chronic diseases, premature mortality, loss of physical function, and depressed m o o d (U.S. Department of
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Health and Human Services, 1996). The American Heart Association labeled physical inactivity the fourth major risk factor for coronary artery disease in 1992 (Fletcher et al., 1992), and recommended that sedentary adults increase participation in moderate intensity physical activity. The U S P H S and other organizations soon followed, with public health recommendations for physical activity in guidelines from the Centers for Disease Control and Prevention and the American College of Sports Medicine ( A C S M ) (Pate et al., 1995); the National Institutes of Health Consensus Development Panel on Physical Activity and Cardiovascular H e a h h (1996); and the Surgeon General's report on physical activity and health (U.S. Department of Health and H u m a n Services, 1996). These various recommendations can be summarized to create a consensus public health recommendation for physical activity: All sedentary adults should accumulate at least 30 minutes of at least moderate-intensity physical activity over the course of most, preferably all, days of the week. The n e w features of this consensus recommendation include the concept of intermittent activity (i.e., activity does not have to be done aU at one time), and the focus on moderateintensity activities. "Moderate intensity" is defined in various ways in the different reports, but for the vast majority of sedentary adults it simply means moderate to brisk walking. This can be further specified as walking 2 miles in 30-40 minutes, or walking at a pace of 15-20 minutes per mile. In other words, three walks of 10 minutes each meet the consensus recommendation for daily physical activity. The advantage of the recommendation is that it allows for a wide variety of options for increasing physical activity. In order to be beneficial, activity does not have to be done at a high intensity, in a special place such as a gymnasium or tennis court, or done all in one session. This has led to the concept of "lifestyle physical activity," in which sedentary individuals are encouraged to reengineer some physical activity back into their daily routines, to replace the reduction in daily energy expenditure caused by the increasing mechanization of modern life.
LIFESTYLE P H Y S I C A L ACTIVITY I N T E R V E N T I O N S Several studies have evaluated the effectiveness of lifestyle physical activity, compared with structured activity, on health outcomes (Andersen et al., 1999; Jakicic, W i n g , Butler, & Robertson, 1995). Project Active w a s a 24-month intervention that compared the heahh effects of a hfestyle physical activity program (i.e., "lifestyle") with a more traditional, gymbased exercise program (i.e., "structured") (Dunn et al., 1999). Participants in both groups received 6 months of intensive intervention, followed by 18 months of minimal maintenance intervention consisting of periodic group activities, a monthly activities calendar, and a quarterly newsletter about physical activity. Lifestyle participants (n = 121) were asked to build a m i n i m u m of 30 minutes of (at least) moderate-intensity activity into their daily routine on most days of the week. The lifestyle intervention w a s based on the transtheoretical model of behavior change (Prochaska &; DiClemente, 1983) and used social-cognitive theory (Bandura, 1986) to shape physical activity behavior according to each individual's motivational readiness for change. At randomization and monthly for thefirst6 months, participants were assessed on motivational readiness for physical activity and given a stage-matched physical activity manual. During the initial 6 months, lifestyle participants attended weekly group meetings at which they were taught to incorporate activities of at least moderate intensity into their daily lifestyle. The lifestyle curriculum is presented in Table 13.1. During the maintenance phase, lifestyle participants were encouraged to continue their physical activity.
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Exercise and Weight M a n a g e m e n t T A B L E 13.1. Project Active Curriculum—Intensive Phase Session title
Activity/discussion topic
Home assignment
1
Getting to K n o w You
Brainstorming about physical inactivity
Personal Time Study
Increasing knowledge
2
Coming U p with a Plan
2-minute walk/finding opportunities
Plan for 2-Minute Walks
Increasing knowledge. substituting alternatives, committing yourself
3
Uncovering Barriers and Benefits
Brainstorming barriers and benefits to becoming physically active
Personal Priorities
Comprehending benefits. increasing healthy opportunities
4
Barriers—Over, Under, Around, and Through
Problem solving to eliminate barriers
Getting Creative
Comprehending benefits. increasing healthy opportunities
5
Energy Expenditure— What It's Worth
Moderate, hard, and very hard activity/calculating energy expenditure
Energy Expenditure Chart
Increasing knowledge
6
Linking It Together to Set Goals
Short- and long-term goals
Ready? Set Goals!
Increasing knowledge. committing yourself
7
Enlisting Support
W h o supports you?/types of social support
Recruiting M y Support Troops
Enlisting support, committing yourself
8
Getting Confident— I Can D o It! I Will D o It!
Confidence building
Confidence Building
Increasing self-efficacy
9
Scavenging for Physical Activity
T e a m scavenge for physical activity
Scavenging for Physical Activity
Week
10 11 12 13
Different types of reinforcement Lapsing? ¥= Relapsing Defining lapse, relapse. collapse # Collapsing Defining stress and Stress Management coping strategies Introducing Digi-Walker, Goal Setting monitoring activity Revisited Rewarding Yourself
14
Time Management
15
Strategies for finding physical activity opportunities in your community Physical Activity Fair Celebration of progress by sharing with others Scavenger hunt From HunterGatherers to InformationGatherers
16 18
Scouting Physical Activity in Your Community
Organizingtime/thevalue of time
Behavioral/cognitive processes
Increasing healthy opportunities, substituting alternatives Rewarding yourself. Rewards for Reaching Goals committing yourself Increasing self-efficacy. Planning for High-Risk Situations substituting alternatives Substituting alternatives, Coping with Stress comprehending benefits Reminding yourself. Step-by-Step or Minutes of Activity committing yourself Weekly Activity Log Decision making, Time Management increasing healthy opportunities, substituting alternatives Caring about Opportunities I Have Found in M y consequences to others. Community enlisting social support Physical Activity Pair Committing yourself, increasing self-efficacy Increasing knowledge, From HunterGatherers to enlisting social support. Informationsubstituting alternatives Gatherers (continued)
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T R E A T M E N T O F A D U L T OBESITY T A B L E 13.1 continued
Week
20
Activity/discussion topic
Session title
22
Jacli Be Nimble, Jill Cognitive restructuring Be Quick, We'll Keep jumping over the Candlestick Potluck Volleyball and potluck
24
Onward
Review of past sessions and looking ahead— doing things on your own
Home assignment
Behavioral/cognitive processes
Talking to Yourself
Substituting alternatives, comprehending benefits
Planning Your Potluck The Things I Need to D o to Stay Active
Enlisting social support, substituting alternatives Increasing knowledge, warning of risks, comprehending benefits, rewarding yourself
During the first 6 months, structured participants (n = 114) were asked to exercise 3-5 days per w e e k for at least 30 minutes per session under supervision. They received a free membership to the Cooper Fitness Center, and a m e m b e r of our staff w a s available several hours each day in the fitness center. T h e exercise counselor talked with the participants about the appropriate intensity and duration of exercise sessions. Structured participants were encouraged to continue their exercise o n their o w n during the maintenance phase. Participants in both groups had similar improvements in physical activity, cardiorespiratoryfitness,blood pressure, and body composition from baseline to 2 4 months (see Figures 13.1 and 13.2). Both groups significantly reduced their body fat percentage (by 2 . 3 9 % and 1 . 8 5 % in the hfestyle and structured groups, respectively), although participants in neither group lost weight. T h e fact that the Project Active intervention did not produce weight loss is not surprising, because the intervention did not focus o n changing diet. These results suggest that a lifestyle physical activity program is as effective as a structured exercise prog r a m in improving physical activity and health outcomes. Long-term maintenance of physical activity in Project Active w a s associated with small weight losses. Participants were asked to indicate w h a t percentage of the weeks (between months 6 and 24) they were physicaUy active at least 3 0 minutes per day, at least 5 days per week. Participants in both groups w h o reported being active at least 7 0 % of the time had greater decreases in weight and body fat than participants w h o were active less than 7 0 % of the time. Participants w h o maintained their activity at least 7 0 % of the time lost 1 kg, whereas participants w h o maintained theh activity less than 3 0 % of the time gained 2.5 kg. This very large difference of 3.5 kg, which occurred over a relatively short period of 18 months, is a good example of the cumulative effect of modest amounts of daily physical activity.
Lifestyle Activity Plus Diet The effectiveness of lifestyle activity, compared with structured activity, on weight loss was evaluated a m o n g 4 0 obese w o m e n (mean B M I = 32.9 kg/m^) w h o participated in a 16-week cognitive-behavioral weight loss program, including a low-calorie, low-fat diet of approximately 1,200 kcal/day (Andersen et al., 1999). Lifestyle activity participants were asked to increase their physical activity by 3 0 minutes per day o n most days of the w e e k by building several short bouts of activity into theh day (e.g., taking the stairs instead of the elevator). Structured activity participants were instructed to attend three step aerobics classes per
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Systolic Diastolic 0 -1 --2 -O) X E E
-3 --4 -5 -\ Lifestyle I Structured
-6 --7 --
p < 0.01 within group
Weight
Percent Body Fat
1.5
w E ra O) o
C u 0) Q. -1.5
p < 0.001 within group FIGURE 13.1. The 24-month changes in blood pressure (upper panel) and weight and body composition (lower panel) for Project Active participants. Data from Dunn et al. (1999).
week. Participants in both groups were asked to exercise on their o w n during the 1-year follow-up period. During the 16-week treatment phase, participants in both groups lost similar amounts of weight (8.3 ± 3.8 kg in the structured group vs. 7.9 ± 4.2 kg in the lifestyle group), but during the 1-year follow-up, lifestyle participants regained significantly less weight (0.08 ± 4.6 kg) than structured participants (1.6 ± 5.5 kg). These results suggest that a lifestyle physical activity program is as effective in promoting weight loss, and is potentially more effective in maintaining weight loss, compared with a structured exercise program.
Short Bouts of Activity One hundred and forty-eight sedentary, overweight women participated in an 18-month behavioral weight loss program with three treatment groups: (1) long-bout exercise; (2) multiple short-bout exercise; or (3) multiple short-bout exercise with exercise equipment (a treadmiU) in the h o m e (Jakicic, Winters, Lang, & W i n g , 1999). All participants received a
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— Lifestyle -•- Structured
« p b H u
time in months
Lifestyle -•- Structured
c E
O)
time in months
FIGURE 13.2. Changes in energy expendimre (upper panel) and cardiorespiratory fitness (lower panel) for Project Active participants. From Dunn et al. (1999). Copyright 1999 by the American Medical Association. Reprinted by permission.
behavioral intervention consisting of caloric and fat restriction and regular group treatment meetings that focused on behavioral strategies for weight loss. All participants were instructed to exercise 5 days per week, beginning with 2 0 minutes per day and progressing to 4 0 minutes per day by week 9. Participants in the long-bout (LB) group were asked to complete their exercise sessions in one long bout. Short-bout (SB) participants were asked to complete their activity in several 10-minute bouts per day. Short-bout plus exercise equipment (SBEQ) participants were provided with a treadmill in their h o m e and asked to complete their activity in several 10-minute bouts per day. Results indicated no difference in weight loss between the L B and SB groups at month 6 (8.2 kg vs. 7.5 kg, respectively) or at m o n t h 18 (5.8 kg vs. 3.7 kg, respectively). There were also no differences between the S B E Q and SB groups in weight loss at 6 months (9.3 kg vs. 7.5 kg, respectively). However, at 18 months, the S B E Q group had significantly greater weight loss (7.4 kg) than the SB group (3.7 kg). There were no differences in weight loss at 6 or 18 months between the L B and S B E Q groups. These results suggest that short bouts of physical activity are effective in promoting weight loss. Providing exercise equipment in the h o m e appears to improve the long-term maintenance of physical activity, perhaps by providing a convenient opportunity to build activity into the daily routine. Individuals in all three groups w h o exercised more than 200
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minutes per week throughout the program lost significantly more weight (13.1 kg) than individuals w h o exercised 150-200 minutes per week (8.5 kg) or less than 150 minutes per week (3.5 kg). These results highlight the importance of regular physical activity for weight loss.
IS O B E S I T Y A N I N D E P E N D E N T P R E D I C T O R O F M O R B I D I T Y A N D M O R T A L I T Y ? There is consensus that individuals at higher BMI levels have increased risk for several chronic diseases (principally cardiovascular diseases and Type 2 diabetes) and for early mortality. Evidence to support this consensus comes primarily from prospective epidemiological investigations in which height and weight were measured (either directly or by selfreport) in a cohort that was followed for morbidity and mortality. There is near-universal agreement in these studies that individuals at higher levels of B M I or some other index of obesity were more hkely to develop clinical endpoints or die. W e think that the results from these studies m a y be affected by confounding. W e k n o w that overweight and obese individuals are more likely than normal-weight persons to be sedentary and unfit (Cooper et al., 1976; Gibbons, Blair, Cooper, & Smith, 1983). In our Aerobics Center Longitudinal Study cohort, there was a strong direct association between B M I and low cardiorespiratory fitness (Barlow, Kohl, Gibbons, & Blair, 1995; see Figure 13.3). In our study, 1 0 % or fewer of lean individuals were in the low-fitness category. Conversely, of those with a B M I > 4 0 kg/m^, about 8 0 % of the w o m e n and more than 9 0 % of the m e n were unfit. However, m a n y obese individuals (BMI S: 30 kg/m^) were at least m o d erately fit and, as will be shown in the next section, did not have elevated risk for mortality. There is also n o w ample evidence that sedentary living habits and low levels of cardiorespiratory fitness increase risk for mortality and for the same chronic diseases as are associated with obesity. Therefore, there is a classic case of potential confounding for these two exposures. O n e might assume that investigators studying obesity and health would account for physical activity in their analyses. However, this has not been the case. In m a n y of the studies on obesity and health, physical activity was not mentioned at all, and w h e n it was included, it was measured by crude and imprecise methods.
Physical Activity, Fitness, Obesity, and Mortality W e decided to evaluate the specific independent contributions of activity and obesity as predictors of mortality. In the Aerobics Center Longitudinal Study, w e had the opportunity to follow w o m e n and m e n w h o came to the Cooper Clinic for medical evaluations. A distinguishing feature of our study was that all participants completed a maximal exercise test on a treadmill at their baseline examination. W e used data from this objective laboratory test to classify individuals on cardiorespiratory fitness. Performance on this treadmill test is highly correlated with maximal oxygen uptake (r - 0.92) (PoUock et al, 1976), which is the hallmark of adaptation to exercise training ( A C S M , 1998). W e consider data from the treadmill test to be an excellent overall indicator of exercise habits over the weeks or months prior to the test. Although several studies found low to moderate correlations (r = .2 to .5), this was attributable primarily to crude measures of physical activity in these studies. W e found coefficients ranging from .66 to .83 for physical activity as a predictor of treadmill test performance, w h e n daily measures of physical activity were obtained over the 6 months prior to the exercise test (Paffenbarger, Blair, Lee, & Hyde, 1993). In ourfirstreport onfitness,obesity, and mortality, w e tracked mortality in 25,389
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S3
18.5-24.9
25.0-29.9
30.0-34.9
35.0-39.9
>=40
B M I kg/m^
18.5-24.9 25.0-29.9 30.0-34.9 35.0-39.9
>=40
B M I kg/m2 FIGURE 13.3. The association between body mass index (BMI) and the prevalence of low cardiorespiratory fitness (dark area of the figure) in 6,840 w o m e n (upper panel) and 23,190 men (lower panel) w h o were free of coronary heart disease, cancer, and abnormal electrocardiograms. The number of individuals across the B M I strata of 18.5-24.9, 25.0-29.9, 30.0-34.9, 35.0-39.9, and > 40 were 5,499, 959, 262, 83, and 37 for women, and 9,838, 10,544, 2,308, 361, and 139 for men. Data from Barlow, Kohl, Gibbons, and Blair (1995).
m e n for an average of 8.5 years after their baseline examination at the Cooper Clinic (Barlow et al., 1995). W e classified the least fit 2 0 % of the m e n as "unfit" and the remainder as "fit," and also assigned them to normal, overweight, or obese categories based on their B M I . A summary of the results is presented in Table 13.2. Mortality rates were not elevated in m e n in the higher B M I categories if they werefit,and obese m e n w h o werefithad much lower death rates than normal-weight m e n w h o were unfit. A concern with the results of thisfirststudy w a s that the obese m e n w h o werefitmight have been muscular rather than fat, and this could have led to misinterpretation of the data. W e addressed this issue in a follow-up investigation in which body fatness rather than B M I was measured (Lee, Blair, & Jackson, 1999). Body composition w a s determined by hydrostatic weighing, seven skinfold measurements, or both. W e classified the m e n as lean (body fat < 1 6 . 7 % ) , normal (body fat = 1 6 . 7 % - 2 4 . 9 % ) , or obese (body fat > 2 5 . 0 % ) , and further stratified the data by fitness group. Results of the analyses are s h o w n in Figure 13.4. The findings are similar to those from the earlier report on B M I ,fitness,and mortality. Fit men in each fatness stratum had substantially lower risk of cardiovascular disease and all-cause mortaUty than unfh m e n in the same fatness stratum. F h but obese m e n had lower mortali-
Exercise and Weight Management
295
TABLE 13.2. Age-Adjusted Relative Risks for All-Cause Mortality by Fitness and Body Mass Index (BMI) Strata, 25,389 M e n , Aerobics Center Longhudinal Study Fitness level
Number of deaths
Age-adjusted relative risks
9 5 % confidence interval
17,178 men with B M I < 27 kg/m^
Low Moderate High
133 180 119
1.0 0.49 0.34
0.31-0.76 0.21-0.57
5,277 men with B M I = 27-30 kg/m^
Low Moderate High
63 67 17
1.0 0.61 0.40
0.38-0.96 0.24-0.68
2,934 men with B M I > 30 kg/m^
Low Moderate-high
75 19
1.0 0.29
0.17-0.49
Note. The data are from Barlow, Kohl, Gibbons, and Blair (1995).
ty risk than lean m e n w h o were unfit. A similar pattern of results w a s observed for a crosstabulation of fitness and waist circumference in the 14,043 m e n with this measurement. W e also compared l o w cardiorespiratory fitness to other established risk factors, such as baseline cardiovascular disease or diabetes, elevated blood pressure or cholesterol, and smoking, as predictors of cardiovascular disease and all-cause mortality in normal-weight, overweight, and obese m e n (Wei et al., 1999). W i t h extended mortality surveillance, w e n o w have m o r e than 1,025 deaths in 25,714 m e n followed for an average of about 10 years. W e calculated mortality risks in each weight group for m e n with each of the risk factors mentioned above. In each analysis, normal-weight m e n without the risk factor c o m prised the reference group, and risk of mortality for m e n with the risk factor w a s calculated in each of the weight groups. N o t surprisingly, baseline cardiovascular disease w a s the strongest predictor of mortality of the various predictors considered in this study. A s u m m a r y of mortality risks for each of the other predictors is presented in Figure 13.5. For each of the predictors, there w a s a gradient of risk from the reference group across normal-weight, overweight, and obese m e n . The relative risk for mortality in obese m e n w a s similar for each of the risk predictors. L o w cardiorespiratory fitness w a s as strongly associated with mortality as w a s having diabetes at baseline, and this w a s observed in both overweight and obese m e n .
Summary of Findings Overweight and obesity d o not appear to increase risk of cardiovascular disease and allcause mortality in m e n w h o are fit. Although the prevalence of acceptable levels of fitness is progressively lower with higher levels of B M I , there are m a n y overweight and obese individuals w h o are fit. O u r studies have limitations in that the published data are from men, although w e n o w have data from preliminary analyses, as well as a review of the literature, that s h o w simUar results in w o m e n (Blair & Brodney, 1999). In addition, our cohort includes few m e m b e r s of minority groups and is d r a w n from middle to upper socioeconomic strata. W e d o not k n o w whether similar results will be found in other demographic groups.
TREATMENT OF ADULT OBESITY
296
Relative Risk 4.5-'] rHFit 1• Unfit
4 3.5 '
2 1.5
1
^^
3 2.5
M
1
•
1
1
1
1 ^n:
1 0.5 0
\ Lean <16.7%
w 1 ^ Normal Obese 16.7-25% >25.0% Body Fat
Relative Risk
Lean <16.7%
Normal Obese 16.7-25% >25.0% Body Fat
FIGURE 13.4. Relative risks for cardiovascular disease (CVD) (upper panel) and all-cause (lower panel) mortality by stratum of percent body fat and cardiorespiratory fitness level in 21,925 men followed for 176,742 person-years of observation (428 deaths, 144 from C V D ) . Relative risks are adjusted for age (single year), examination year, smoking status, alcohol intake, and parental history of coronary heart disease. Unfit men (black bars) were the least fit 2 0 % in each age group, and all other men were classified as fit. Data from Lee, Blair, and Jackson (1999).
It is also possible that other factors (such as smoking habits or subchnical disease) might have confounded the analyses, but such factors would be unlikely to cause associations as strong as those observed. W e also performed analyses o nfitnessand fatness in nonsmoking m e n and obtained similar resuhs (Lee et al., 1999). Furthermore, participants in our study received an extensive clinical evaluation and physical examination, so w e have ample information for evaluating the health status of study participants. Another limitation
Exercise a n d W e i g h t M a n a g e m e n t
297
Relative risk adjusted for age and exam year 5
TC >239
Diabetes
Hypertension
Smolter
Low fit
Comorbidities of Obesity
Relative tisk adjusted for age and exam year 3.S
TC >239
Diabetes
Hypertension
Smolter
Low fit
Comorbidities of Obesity F I G U R E 13.5. Relative risks for cardiovascular disease ( C V D ) (upper panel) and aU-cause (lower panel) mortality in 25,714 m e n followed for 258,781 person-years of observation (1,025 deaths, 4 3 9 from C V D ) . Relative risks were adjusted for age and examination year. T h e reference category in each of the five analyses consisted of normal-weight m e n ( B M I = 18.5-24.9) w h o did not have the specific risk factor examined in the specific analysis. Overweight m e n were those with a B M I of 25.0-29.9, and obese m e n were those with a B M I > 30.0. Data from Barlow, Kohl, Gibbons, and Blair (1995) and W e i etal. (1999).
of the material presented here is that the focus w a s o n the benefits of activity or fitness in delaying mortality. Certainly other deleterious effects of obesity, such as social stigmatization a n d lower quality of hfe, m a y persist even in active a n d fit individuals. M o r e research is needed o n these topics.
CONCLUSION Regular physical activity promotes cardiovascular fitness, delays or prevents weight gain, contributes to weight loss, a n d is crucial for maintaining weight loss. Perhaps the m o s t important m e s s a g e of this chapter is that increased physical activity a n d cardiorespiratory fitness have significant benefits for overweight a n d obese individuals that extend far b e y o n d the contributions of exercise to weight loss a n d m a i n t e n a n c e . O v e r w e i g h t a n d obese indi-
298
T R E A T M E N T O F ADULT OBESITY
viduals should be encouraged to be physically active, whether it makes them slim or not. Available data strongly support the conclusion that activity enhances health and delays mortality in overweight and obese individuals.
ACKNOWLEDGMENTS We thank Ming Wei, MD, MPH, for analyses on the prevalence of low fitness by BMI strata; Melba Morrow for edhorial review; and Stephanie Parker for assistance with figure preparation. The work reported here is supported in part by grants from the National Institutes of Health (Nos. HL48597, HL58608, and AG06945) and Polar Electro Oy.
REFERENCES American College of Sports Medicine (ACSM). (1998). The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, andflexibilityin healthy adults. Medicine and Science in Sports and Exercise, 30(6), 975-991. Andersen, R. E., Wadden, T. A., Bartiett, S. J., Zemel, B., Verde, T. J., Si Franckowiak, S. C. (1999). Effects of lifestyle activity vs structured aerobic exercise in obese women: A randomized trial. Journal of the American Medical Association, 281 (4), 335-340. Bandura, A. (1986). Social foundations of thought and action: A social cognitive theory. Englewood Cliffs, NJ: Prentice-Hall. Batiow, C. E., Kohl, H. W., Ill, Gibbons, L. W., Si Blair, S. N . (1995). Physical fitness, mortality and obesity. International Journal of Obesity, 19(Suppl. 4), S41-S44. Blair, S. N., & Brodney, S. (1999). Effects of physical inactivity and obesity on morbidity and mortality: Current evidence and research issues. Medicine and Science in Sports and Exercise, 31(11, Suppl.), S646-S662. Bouchard, C , Si Blair, S. N . (1992a). Physical activity in the prevention and treatment of obesity and its co-morbidities [Abstract]. Medicine and Science in Sports and Exercise, 31(11, Suppl.), S39. Bouchard, C , Si Blair, S. N . (1999b). Roundtable introduction: Introductory comments for the consensus on physical activity and obesity. Medicine and Science in Sports and Exercise, 31(11, Suppl.), S498-S501. Bouchard, C , Despres, J.-P., & Tremblay, A. (1993). Exercise and obesity. Obesity Research, 1(1), 133-147. Briefel, R. R., Sempos, C. T., McDowell, M . A., Chien, S., Sc Alaimo, K. (1997). Dietary methods research in the third National Health and Nutrition Examination Survey: Underreporting of energy intake. American Journal of Clinical Nutrition, 65(4, Suppl), 1203S-1209S. Centers for Disease Control and Prevention. (1994). Daily dietary fat and total food-energy intakes— N H A N E S III, Phase 1, 1988-91. Journal of the American Medical Association, 271(17), 1309. Cooper, K. H., PoUock, M . L., Martin, R. P., White, S. R., Linnerud, A. C , & Jackson, A. (1976). Physical fitness levels vs. selected coronary risk factors: A cross-sectional study. Journal of the American Medical Association, 236, 166-169. DiPietro, L., Kohl, H. W., Ill, Barlow, C. E., Sc Blah, S. N . (1997). Physical fitness and risk of weight gain in men and women: The Aerobics Center Longitudinal Study [Abstract]. Medicine and Science in Sports and Exercise, 29, SI 15. Drucker, E. (1999). Drug prohibition and public health: 25 years of evidence. Public Health Reports, 114(1), 14-29. Dunn, A. L., Marcus, B. H., Kampert, J. B., Garcia, M . E., Kohl, H. W., IH, Si Blah, S. N . (1999). Comparison of lifestyle and structured interventions to increase physical activity and cardiorespiratory fitness: A randomized ttial. Journal of the American Medical Association, 281(4), 327-334. Fletcher, G. F., Blah, S. N., Blumenthal, J., Caspersen, C , Chairman, B., Epstein, S., Falls, H.,
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Froelicher, E. S. S., Froelicher, V. F., & Pina, I. L. (1992). Position statement: Statement on exercise. Benefits and recommendations for physical activity programs for all Americans: A statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation, 86, 340-344. French, S. A., Jeffery, R. W., Forster, J. L., McGovern, P. G , Kelder, S. H., & Baxter, J. E. (1994). Predictors of weight change over two years among a population of working adults: The Healthy Worker Project. International Journal of Obesity, 18(3), 145-154. Gibbons, L. W., Blair, S. N., Cooper, K. H., Si Smith, M . (1983). Association between coronary heart disease risk factors and physical fitness in healthy adult w o m e n . Circulation, 67(5), 977-983. Jakicic, J. M., Wing, R. R., Butler, B. A., Si Robertson, R. J. (1995). Prescribing exercise in multiple short bouts versus one continuous bout: Effects on adherence, cardiorespiratoryfitness,and weight loss in overweight w o m e n . International Journal of Obesity, 19, 893-901. Jakicic, J. M., Winters, C , Lang, W., Si Wing, R. R. (1999). Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women: A randomized trial. Journal of the American Medical Association, 282(16), 1554-1560. Jeffery, R. W., Sc French, S. A. (1997). Preventing weight gain in adults: Design, methods and one year results from the Pound of Prevention Study. International Journal of Obesity, 21(6), 457-464. Katch, F. I., Si McArdle, W . D. (1993). Introduction to nutrition, exercise, and health. Philadelphia: Lea Si Febiger. Kayman, S., Bruvold, W., & Stern, J. S. (1990). Maintenance and relapse aher weight loss in women: Behavioral aspects. American Journal of Clinical Nutrition, 52(5), 800-807. Koplan, J. P., &: Dietz, W . H . (1999). Caloric imbalance and public health policy. Journal of the American Medical Association, 282(16), 1579-1581. Lee, C. D., Blair, S. N., Si Jackson, A. S. (1999). Cardiorespiratory fitness, body composition, and allcause and cardiovascular disease mortality in men. American Journal of Clinical Nutrition, 69(3), 373-380. Levy, A. S. (1993). Weight control practices of U.S. adults trying to lose weight. Annals of Internal Medicine, 119, 661-666. McGuire, M . T., Wing, R. R., K k m , M . L., Seagk, H. M., Si HUI, J. O. (1998). Long-term maintenance of weight loss: D o people w h o lose weight through various weight loss methods use different behaviors to maintain their weight? International Journal of Obesity, 22(6), 572-577. Miller, W . C , Koceja, D. M., Si Hamilton, E. J. (1997). A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. International Journal of Obesity, 21(10), 941-947. Mokdad, A. H., Serdula, M . K., Dietz, W . H., B o w m a n , B. A., Marks, J. S., & Koplan, J. P. (1999). The spread of the obesity epidemic in the United States, 1991-1998. Journal of the American Medical Association, 282(16), 1519-1522. National Heart, Lung, and Blood Institute (NHLBI). (1998). Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. Obesity Research, 6(Suppl.), 51S-210S. National Institutes of Health (NIH) Consensus Development Panel on Physical Activity and Cardiovascular Heahh. (1996). N I H Consensus Conference: Physical activity and cardiovascular health. Journal of the American Medical Association, 276(3), 241-246. Paffenbarger, R. S., Jr., Blah, S. N., Lee, I.-M., Si Hyde, R. T. (1993). Measurement of physical activity to assess health effects in free-living populations. Medicine and Science in Sports and Exercise, 15, 60-70. Pate, R. R., Pratt, M., Blah, S. N., HaskeU, W . L., Macera, C. A., Bouchard, C , Buchner, D., Ettinger, W., Heath, G. W., King, A. C , Kriska, A., Leon, A. S., Marcus, B. H., Morris, J., Paffenbarger, R. S., Jr., Patrick, K., Pollock, M . L., Rippe, J. M., SaUis, J., & Wilmore, J. H . (1995). Physical activity and public health: A recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. Journal of the American Medical Association, 273, 4 0 2 ^ 0 7 . Pollock, M . L., Bohannon, R. L., Cooper, K. H., Ayres, J. J., Ward, A., White, S. R., & Linnerud, A.
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C. (1976). A comparative analysis of four protocols for maximal treadmiU stress testing. American Heart Journal, 92, 39-46. Prochaska, J. O., & DiClemente, C. C. (1983). The stages and processes of self-change in smoking: Towards an integrative model of change. Journal of Consulting and Clinical Psychology, 51, 390-395. SchoeUer, D. A., Ravussin, E., Schutz, Y., Acheson, K. J., Baertschi, P., Si Jequier, E. (1986). Energy expenditure by doubly labeled water: Validation in humans and proposed calculation. American Journal of Physiology, 250(5, Pt. 2), R823-R830. U.S. Department of Health and H u m a n Services. (1996). Physical activity and health: A report of the Surgeon General. Atlanta, GA: Centers for Disease Control and Prevention. Wei, M., Kampert, J. B., Barlow, C. E., Nichaman, M . Z., Gibbons, L. W., Paffenbarger, R. S., Jr., & Blair, S. N . (1999). Relationship between low cardiorespiratory fitness and mortaUty in normalweight, overweight, and obese men. Journal of the American Medical Association, 282(16), 1547-1553. WiUiamson, D. F., Madans, J., Anda, R. F., Kleinman, J. C , Kahn, H. S., & Byers, T. (1993). Recreational physical activity and ten-year weight change in a U S national cohort. International Journal of Obesity, 17(5), 279-286. World Health Organization (1998). Obesity: Preventing and managing the global epidemic. (Publication No. WHO/NUT/NCD/98.1). Geneva: Author.
1
Behavioral
4
W e i g h t
Control
R E N A R. W I N G
Recently there has been a marked increase in the prevalence of overweight and obesity, resulting in higher rates of obesity-related comorbidities, such as Type 2 diabetes. Effective approaches to the treatment of obesity and overweight are therefore clearly needed. The National Heart, Lung, and Blood Institute ( N H L B I , 1998) has reviewed the empirical literature on obesity and weight control interventions, and published Clinical Guidelines for the Identification, Evaluation, and Treatment of Overweight ( N H L B I Obesity Education Initiative Expert Panel, 1998). A conclusion from this report w a s that interventions combining a low-calorie diet, physical activity, and behavior therapy were most effective for weight loss and maintenance. T h e goals of the present chapter are to provide an update of recent findings related to the behavioral treatment of obesity, and to suggest n e w clinical and research directions that should be pursued.
HISTORICAL O V E R V I E W O F T H E B E H A V I O R A L T R E A T M E N T O F OBESITY Behavioral principles were first applied to the treatment of obesity in the late 1960s and early 1970s (Ferster, Nurnberger, & Levitt, 1962; Stuart, 1967). This approach, which grew out of Learning Theory, assumes that the behaviors related to regulation of body weight—namely, eating and exercise behaviors—have a learned component, and thus can be relearned or modified. In addition, behaviorists beheve that in order to change eating and exercise behaviors, it is important to alter the environmental cues (or antecedents) and the reinforcers that control these behaviors. Early behavioral programs were conducted with minimally overweight individuals and typically lasted 10 weeks. Participants were taught to restrict their eating to one location, to make eating a pure activity (separate from watching T V , reading, etc.), and to monitor situational and emotional cues related to eating. However, specific goals for caloric intake and expenditure were not prescribed. These early programs produced weight losses of approximately 4.5 kg over a 10-week program (Wing & Jeffery, 1979). Over the next t w o decades, behavioral programs were gradually lengthened, such that 301
302
T R E A T M E N T O F ADULT OBESITY
T A B L E 14.1. Summary of Behavioral Weight Loss Treatments Using Conventional Low-Calorie Dkts, 1970-1995 1974 No. of studies included Initial weight (kg) Length of treatment (wk) Weight loss (kg) Length of follow-up (wk) Loss at follow-up (kg)
1984
1990-1995
15
15
14
73.4
88.7 13.2
91.6 26.0
8.4 3.8 5.5 4.0
6.9
9.0
58.4
40.0
4.4
5.2
Hote. Data from Wadden (1993) and Wing (1998).
the initial intensive phase of treatment n o w typically involves 6 months of weekly meetings. Although the specific entry criteria differ across studies, the average participant entering behavioral programs is middle-aged and weighs approximately 9 0 kg. W o m e n are more commonly treated in behavioral programs than m e n , and some studies are specifically restricted to w o m e n . T h e emphasis of the treatment has also shifted to focus explicitly on energy balance. Participants are n o w given specific goals for calorie intake (typically 1,000-1,500 kilocalories [kcal]/day, depending on body weight), and dietary fat gram goals have recently been prescribed, as weU. Similarly, participants are given specific goals for physical activity. These goals are gradually increased until the participant is completing 1,000 kcal/week in activity (equivalent to walking 10 mUes/week). K e y behavioral components of these programs include self-monitoring, stimulus control strategies, problem solving, preplanning, and relapse prevention. With these changes in behavioral programs, weight losses have gradually improved. Table 14.1 shows the weight losses achieved in programs from the 1970s to the 1990s (Wadden, 1993; Wing, 1998). A s shown, there has been m o r e than a doubling in the initial weight loss achieved. O n average, participants in behavioral programs in the 1990s lost 9.0 kg, or approximately 1 0 % of their initial body weight. Unfortunately, there has been less improvement in the maintenance of weight loss. O n average, patients regain more than one-third of their initial weight loss over thefirstyear of follow-up. Thus overall weight loss from entry to a 40-week follow-up averages 5.2 kg. Tables 14.2 and 14.3 summarize the major behavioral weight loss trials that were published since 1996. (Pilot studies, studies with posttreatment randomization that focused on maintenance, and studies conducted with minimal face-to-face contact are omitted from these tables.) A s can be seen, these recent studies have focused largely on comparison of different types of exercise interventions. Participants achieved an average weight loss of 9.6 kg over 21 weeks. These initial weight losses appear comparable to those achieved in 1990-1995. However, the foUow-up period is n o w longer (averaging 18 months), and patients maintained a weight loss of 6.0 kg ( 6 2 % of theh initial weight loss) over this longer follow-up. The foUowing sections of this chapter describe the behavioral studies published since 1996 that focused on changing eating behavior, changing physical activity, and motivational strategies to improve weight loss.
C H A N G I N G EATING B E H A V I O R
In order to lose weight, h is necessary to modify dietary intake. However, the optima etary prescription for weight loss is still unclear. Typically, behavioral weight loss programs
Table 14.2. Behavioral Weight Loss Studies, 1996-1999
Reference
n
(kg)
Characteristics
Duration (mo)
n
Wt. loss (kg)
Duration (mo)
n
Wt. loss (kg)
Andersen et al. (1999) Lifestyle activity Structured exercise
20 20
87
All females; 42.9 yr
4 4
19 19
7.9 8.3
16 16
16 17
7.8 6.7
49 51 48
90
All females; 36.7 yr
6 6 6
37 36 42
8.2 7.5 9.3
18 18 18
37 36 42
5.8 3.7 7.4*
40 41 42
86
29 males, 167 females; 25-55 yr
6 6 6
86% comp.
8.3 6.0 5.6
18 18 18
78% comp.
7.6* 3.8 2.9
6.7 7.9
18 18
10.4 9.3
15 15
Wt.
CO o OJ
Follow-up
Follow-up
Treatment
Pretreatment
Jakick etal. (1999) Long bout Short bout Short boutEquipment Jeffery etal. (1998) SBT SBT + walks SBT + walks + trainer SBT + walks + $ SBT + walks + trainer + $ Perti etal. (1997) Home-based exercise Group-based exercise
6 6
37 36
24 25
88
All females; 48.7 yr
6 6
23 25
Duration (mo)
n
Wt. loss (kg)
4.5 5.1
23 25
11.6* 7.0 (continued)
T A B L E 14.2. continued Pretreatment
Wt. Reference
o
Skenderetal. (1996) Control Diet Exercise Diet + exercise Wadden et al. (1997) Diet Diet + aerobic Diet + resistance Diet + aerobic + resistance
;;
(kg)
127
Duration (mo)
n
3 3 3 3
38 42 43 42
6 6 6 6
All females; 41.3 yr
21 males. 78 females; 45.7 yr
Characteristic Males + females
29 31 31 29
96
40 41 41 41
86
SBT + menu SBT + buy food SBT + hee food Wing etal. (1998) Control Diet Exercise Diet + exercise
40 37 37 40
99
Treatment
All females; 41.1 yr
Follow-up
Follow-up
Wt. loss (kg)
Duration (mo)
n
Wt. loss (kg)
Duration (mo)
n
6.8*
19 30 27
6.8 2.9 8.9
24 24 24
15 25 21
+0.9
6.5*
12 12 12
27 30 29 27
16.7 16.2 16.8 16.3
12 12 12 12
24 28 24 23
14.4 13.7 17.2 15.2
24 24 24 24
21 21 18 17
6.9 8.5
6 6 6 6
35 37 36 40
8.0 12.0* 11.7* 11.4*
18 18 18 18
32 37 37 38
6.9* 7.5* 6.6'-
6 6 6 6
32 35 33 31
12 12 12 12
29 33 28 30
24 24 24 24
31 35 31 32
0.7
W t . loss (kg)
2.7 2.2
10.1
8.6
WingetaL (1996)
SBT
Hote. SBT, standard behavioral treatment. *Treatment groups differ in weight loss at p < 0.05
1.5 9.1*
2.1 10.3*
3.3
0.3 5.5*
0.4 7.4*
0.3 2.1 +1.0
2.5
Behavioral Weight Control
305
TABLE 14.3. Summary of Behavioral Weight Loss Studies, 1996-1999 No. of studies Number of treatment conditions" Length of treatment (wk/mo) Weight loss (kg) Length of final follow-up (wk/mo) Weight loss (kg)
9 28 21/5.25 9.61'' 74.2/18.5 5.97^
"Excluding control groups and exercise-only groups. ''If the study by Wadden et al. (1998) is omitted, the average weight loss during treatment is 8.45 kg, and the average weight loss at follow-up is 5.54 kg.
encourage participants to c o n s u m e 1,000-1,500 kcal/day. Often dietary fat intake is restricted to 2 0 % - 3 0 % of calories. Several studies conducted in the 1980s and early 1990s examined the effectiveness of m u c h m o r e stringent dietary restriction, in the form of verylow-calorie diets ( V L C D s ) ( W a d d e n , Foster, & Letizia, 1994; W a d d e n &: Stunkard, 1 9 8 6 ; Wing, Blair, M a r c u s , Epstein, & Harvey, 1 9 9 4 ; W i n g et al, 1991). V L C D s provide 400-800 kcal/day a n d are c o n s u m e d as a liquid formula or as lean meat, fish, and fowl. These diets were s h o w n to be effective for initial weight loss, with patients losing an average of 20 kg over 12 weeks (Wadden, Stunkard, & Brownell, 1983). However, two major problems were identified. First, these dietary regimens were expensive, because they necessitated ongoing medical monitoring to ensure their safety. Second, even w h e n a V L C D was used in combination with behavioral training, participants tended to regain weight rapidly after termination of the V L C D . W a d d e n and colleagues (1994) attempted to curtaU this weight regain by providing a full year of weekly behavioral treatment. Wing, Blair, Marcus, Epstein, and Harvey (1994) utiUzed an intermittent V L C D approach, with 12 weeks of V L C D followed by 12 weeks of refeeding, and then another 12 weeks of V L C D followed by 12 weeks of refeeding. At the end of both the W a d d e n and colleagues (1994) and W i n g and colleagues (1994) studies, no significant benefits of the V L C D compared to a more balanced, less restricted diet of 1,000-1,500 kcal/day were observed.
Structured Meal Plans Behaviorists have recently been experimenting with several n e w approaches to the diet. O n e approach is to provide participants with more structured meal plans and grocery lists, which m a y serve as models of h o w to achieve a low-calorie, low-fat intake. W i n g and colleagues (1996) analyzed the effectiveness of such an approach in a study of 163 w o m e n . These w o m e n were randomly assigned to one of four groups. Thefirstgroup was given a standard behavioral treatment program, with a goal of consuming no more than 1,000-1,500 kcal/day, goals for physical activity, and standard behavioral strategies. The second group received the identical behavioral program with the same calorie goal; in addition, participants were given structured meal plans that told them exactly what they should consume forfivebreakfasts and five dinners each week, and a shopping list to guide them in purchasing the required foods. The third and fourth groups received the same behavioral program and the same meal plan, but at each weekly meeting they were also given a box of food that contained exactly what they should eat forfivebreakfasts andfivedinners during the next week. Group 3 participants shared the cost of the food with the study, and those in group 4 received the food free of charge. As seen in Table 14.2, weight losses both at the end of the 6-month intervention and at 12-month follow up were significantiy better in groups 2-4 than in group 1. Groups 2-A
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also reported more regular meal patterns and changes in the types of foods available in the home.
Meal Replacements Another approach to strengthening the diet component of behavioral weight loss programs has been to use prepared meals or liquid meal replacements. These diets differ from the earlier V L C D s in that the calorie level of these diets is at least 900 kcal/day, reducing the need for medical monitoring, and at least some meals each day are consumed as regular food. W a d d e n and his colleagues (Wadden et al., 1997; W a d d e n , Vogt, Foster, & Anderson, 1998), in their study of exercise strategies, used a 900- to 925-kcal/day diet that consisted of four servings/day of a hquid meal replacement (150 kcal/meal) and a dinner meal of a shelf-stable entree (280-300 kcal/day) plus 2 cups of salad. After 16 weeks on this diet, the liquid meals were reduced, and calories were increased to 1,250 kcal/day; at week 22, the calories were further increased to 1,500 kcal/day, and participants selected their o w n foods. The diet-only group in this study was seen weekly for 28 weeks and then biweekly during weeks 29-48. Subjects in the diet-only condition lost 16.7 kg at 6 months, and maintained a weight loss of 14.4 kg at 12 months. In the 7 2 % of participants w h o completed the 2-year follow-up, the average weight loss was 6.9 kg. A simUar regimen involving a combination of liquid formula (SlimFast) and regular food was used by Ditschuneit, Flechtner-Mors, Johnson, and Adler (1999). Participants w h o were randomly assigned to the SlimFast condition were instructed to consume two SlimFast meal replacements each day and to have a healthy dinner meal. These participants lost 7 kg over the first 3 months of the program, compared to 1 kg in subjects prescribed the same number of calories with a free-choice diet. Both groups were then maintained on a diet of 1,200-1,500 kcal/day, which included one meal and one snack each day of SlimFast products. Both groups were seen monthly over the next 24 months. Weight losses at the end of 2 4 months averaged 10.2 kg for the group that was prescribed SlimFast throughout, and 7.7 kg for the group that started on regular food and was then switched to SlimFast. Although such weight losses at 2 years are excellent, the fact that weight data were available for only 6 3 % of the sample limits the conclusions that can be drawn. However, these studies all suggest the benefit of simplifying dietary adherence by providing at least some of the food to participants.
C H A N G I N G P H Y S I C A L ACTIVITY Physical activity is the component of behavioral treatment that has received the greatest attention since 1995. This emphasis is based on the fact that physical activity level has been the most consistent predictor of the long-term maintenance of weight loss (Pronk & Wing, 1994). Randomized studies have likewise supported the benefit of diet plus exercise versus diet alone, although the differences between these conditions are often not statistically significant. This literature on the effect of exercise on weight loss and maintenance has been examined in two reviews ( N H L B I Expert Panel, 1998; Wing, 1999). Both reviews concluded that exercise alone (without diet) produces a small weight loss of approximately 2 kg; in 6 of 10 studies comparing exercise alone to a no-exercise control condition, the exercise group experienced significantly greater weight loss than the control group. In contrast, only 2 of 13 studies that compared diet only to diet plus exercise found a significant effect of exercise on initial weight loss (4 months to 1 year), although the dhection of the difference
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consistently favored the combination of diet plus exercise. FinaUy, most important is the issue of whether diet plus exercise improves long-term maintenance of weight loss. The N H L B I Expert Panel (1998) discussed three studies related to this issue and noted that in all three, the combination condition produced a long-term weight loss 1.5-3 kg greater than that produced by diet or exercise alone. W i n g (1999) identified six studies with a 1-year or longer follow-up interval that compared diet only to diet-plus-exercise. Although all six studies showed greater long-term weight loss in the diet-plus-exercise condition, only two of the six studies indicated a statistically significant difference in weight loss for the diet-plusexercise condition versus the diet-only condition.
Long-Term V/eight Loss Results of three of the studies comparing the long-term effects of diet plus exercise versus diet alone have been reported since 1995 (Table 14.2). Skender and colleagues (1996) reported 2-year results of a study comparing diet, exercise, and the combination of diet plus exercise. At 2 years, the diet-plus-exercise group maintained a weight loss of 2.2 kg, and the diet-only group w a s 0.9 kg over baseline weight. This difference between groups was not significant. T h e fact that only 3 6 % of the diet-only group and 5 0 % - 5 8 % of the other groups attended this follow-up limits these conclusions. Similarly, W i n g and colleagues presented the 2-year results of our study with individuals w h o had a family history of diabetes (Wing, Venditti, Jakicic, PoUey, &c Lang, 1998). In this study, the behavioral treatment program included 6 months of weekly meetings, 6 months of biweekly meetings, and then two 6-week refresher courses in year 2. The diet-only group and the diet-plusexercise condition started their programs with 8 weeks of a structured 800- to 1,000kcal/day diet, which w a s then m a d e more flexible and gradually increased in calories to 1,200-1,500 kcal/day. Participants in the exercise condition exercised together as a group during each of their treatment sessions; they were instructed to also exercise on their o w n and to achieve a goal of 1,500 kcal/week of physical activity. The diet-only group and the diet-plus-exercise condition experienced similar excellent initial weight losses (9.1 kg and 10.3 kg, respectively). These groups maintained 6 0 % and 7 2 % , respectively, of this initial weight loss at 12 months. However, both groups regained a great deal over the 1- to 2year follow-up. At the end of the 2-year study, there were no significant differences in weight loss between groups, and only the diet-plus-exercise group was significantly below baseline levels. Although attendance at the annual assessments w a s good in this study, many participants ceased to attend the treatment sessions after the initial 6 months. This poor participation in the treatment m a y have led to the poor long-term outcome in this study. Finally, the third post-1995 study that compared diet only to diet plus exercise also found no significant long-term differences in weight loss for these two interventions (Wadden et al., 1997, 1998). W a d d e n and colleagues (1997) randomly assigned 128 overweight w o m e n to diet alone, diet plus aerobic exercise, diet plus strength training, or diet plus aerobic and strength training. All groups received the same 48-week program with weekly sessions for 28 weeks and then biweekly sessions, and aU groups consumed the same diet of 900-925 kcal'day (see above) for weeks 2-17. The exercise conditions participated in three supervised exercise sessions/week for thefirst6 months and then two sessions/week for the second half of the study. O f the 128 participants, 99 completed the 12-month study. Weight losses at both 6 months (16 kg) and 12 months (13.7-17.2 kg) were outstanding in this study, but there were no statistically significant differences between treatment conditions. Moreover, the 2-year follow-up completed on 7 7 of the initial 128 subjects ( 6 0 % ) again showed no benefh of diet plus any type of exercise versus diet alone ( W a d d e n et al, 1998). The authors noted that participants w h o continued ex-
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ercising at 2 years had better weight losses than those who stopped exercising. However, by 2 years, there were an equal proportion of participants in each group w h o reported exercising. These three recent studies, thus, all raise questions about the widely held belief that treatments that focus on diet plus exercise produce better long-term weight losses than diet only. They suggest, however, that the failure to confirm the benefits of the combination intervention m a y be due primarily to the difficulty of getting participants to maintain theh physical activity over the long term. Several other recent studies have focused specifically on this issue and tried to determine h o w best to promote long-term adherence to physical activity.
Improving Exercise Adherence Studies by Andersen and colleagues (Andersen, Frankowiak, Snyder, Bartlett, & Fontaine, 1999) and Perri and colleagues (Perri, Martin, Leermakers, Sears, & Notelovitz, 1997) addressed the question of whether a supervised group exercise program, conducted at a designated location, was more or less effective than a home-based or lifestyle approach to physical activity. Group approaches allow for greater social support from peers and more guidance and reinforcement from the group leader. However, the extra time commitment of having to travel to the exercise location, as well as the fact that the exercise sessions are held at a designated time or times m a y limit the long-term appeal of this approach. Perri and colleagues (1997) recruited 49 overweight w o m e n (mean age = 49 years, m e a n baseline weight = 8 8 kg) and randomly assigned them to behavioral treatments that included group-based or home-based exercise. Both groups attended weekly 2-hour meetings for the first 26 weeks and then biweekly sessions during weeks 27-52. Both were prescribed a diet of 1,200 kcal/day, with 2 5 % of calories from fat. Participants in the group exercise condition were asked to exercise at a clinical facility three times/week for the first 6 months and then two times/week. Exercise classes were also held before each weekly or biweekly behavioral treatment session. The home-based group w a s instructed to complete 30 minutes of exercise 5 days/week. These participants completed no group exercise at any time during the study. N u m b e r of minutes of exercise per week was similar in the two conditions for months 1-6 (104 minutes/week in both groups); however, subjects in the homeexercise condition completed more minutes of activity during months 7-12. The two groups experienced similar weight loss during thefirst6 months of the program, but the homebased group had better maintenance of this weight loss from 6 to 15 months. Overall weight loss from months 0 to 15 was significantly greater in the h o m e exercise condition than in the group exercise condition (11.7 kg vs. 7.0 kg; p < .05). The dropout rate was also greater in the group program, and was frequently noted to be due to the difficulty of traveling to exercise classes. Andersen and colleagues (1999) tested a similar hypothesis in a study of 40 overweight w o m e n (mean age = 43 years, m e a n weight at entry - 87 kg). Participants in this study attended weekly group behavioral sessions for 16 weeks and were prescribed a 1,200kcal/day low-fat diet. The diet-plus-structured-exercise group participated in three aerobics classes a week (estimated expendhure of 450-500 kcal/session) for the first 16 weeks. They were then given tapes of their exercise sessions and instructed to continue exercising on their o w n at home. The diet-plus-lifestyle-activity group was instructed to complete 30 minutes of moderate-intensity activity on most days of the week. Accelerometers were used to document physical activity level, and participants were given a graph of their activity at the end of each weekly group meeting. At week 16, the average weight loss of the lifestyk group was 7.9 kg, and that of the aerobic group was 8.3 kg. Participants in the lifestyle
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group regained 0.08 kg from month 6 to 1-year follow-up (week 68), and the aerobics group regained 1.6 kg (p = .06). Considering these two studies together, the most appropriate conclusion seems to be that either a home-based or a clinic-based activity program can be utilized during the initial phase of treatment, but that the home-based program m a y have some long-term advantage. The weight losses of the home-based condition in the Perri and colleagues (1997) study stand out as the best long-term outcome across these two studies. This observation m a y suggest the importance of using a home-based exercise prescription in combination with ongoing biweekly group behavioral treatment sessions for maintenance of weight loss.
Short-Bout Activity Several other approaches to improving long-term adherence to physical activity have also been investigated. W e (Jakicic, W i n g , Butler, &c Robertson, 1995) reported that prescribing exercise in multiple short bouts m a y help overweight individuals initiate an exercise program. This study found that participants w h o were instructed to complete four 10-minute bouts of activity had better adherence to exercise and better weight losses than individuals w h o were instructed to exercise in one 40-minute bout. Since this initial study lasted only 6 months, Jakicic, W i n g , and Winters (1999) replicated this intervention more recently but continued the treatment for 18 months. In addition, a third treatment w a s examined, in which subjects were instructed to complete their activity in four 10-minute bouts, but were given a h o m e treadmill to facilitate this activity. This study confirmed the benefits of initially prescribing exercise in multiple bouts, but showed that after the initial weeks of the program, this benefit w a s n o longer observed. By 18 months, there were no differences between the short-bout and long-bout conditions for adherence to physical activity or for weight loss. However, providing exercise equipment to participants did have a positive long-term effect. The short-bout group that w a s given h o m e exercise equipment reported the best maintenance of physical activity during months 12-18, as well as the best overall weight loss.
Personal Trainer Physical activity equipment m a y modify the h o m e environment and serve as a cue to exercise. Another approach to modifying the antecedents for exercise is to use a personal trainer or coach w h o calls participants to remind them to exercise and exercises with the participants, thus modeling and supporting the activity. Jeffery, Wing, Thorson, and Burton (1998) examined this antecedent-control approach and compared its effectiveness to that of changing the consequences for activity by paying participants small incentives for exercise. The participants were 196 overweight individuals (29 m e n and 167 w o m e n ) , with a m e a n baseline weight of 86 kg, w h o were randomly assigned to one of five conditions. All five groups received a standard behavioral weight loss program, with weekly meetings for 6 months, biweekly meetings for 6 months, and then monthly meetings for the final 6 months. The exercise prescription for all groups w a s to gradually increase physical activity to a goal of 1,000 kcal/week. G r o u p 1 participants were given this goal and instructed to complete their exercise o n their o w n at h o m e . Group 2 w a s invited to three exercise sessions per week; these sessions were conducted at a local track, and participants walked 3 miles at each session. G r o u p 3 participants were given "personal trainers" to help increase their adherence to the exercise sessions. These trainers called the participants to remind them to participate in the exercise session and met them at the track to walk with them; m a k e u p ses-
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sions were also arranged. Participants in group 4 were paid $l-$5 per session for attending the scheduled activity sessions. Group 5 received the combination of the personal trainers and the incentives for attending the exercise sessions. The study suggested that the antecedent control (trainers) and the consequent control (payment) were equally effective approaches for increasing attendance at exercise sessions. Either approach used alone doubled attendance at these sessions, and the combination of the rwo resulted in a tripling of exercise attendance. However, despite the benefits for attendance, these procedures had no effect on overall physical activity level. All five groups reported comparable levels of activity, all approximating the 1,000-kcal goal that was assigned. The most unexpected finding from this study w a s that group 1—the group given the standard behavioral treatment with no supervised exercise sessions—had the best long-term weight loss. This finding supports the studies described above that showed benefits of home-based physical activity interventions. The fact, however, that all groups reported similar levels of activity raises questions about this interpretation. Another possibility is that the increased emphasis on exercise in groups 2-4 decreased the focus on weight loss in these conditions.
Amount of Exercise The Jeffery and coUeagues (1998) study also raised the possibility that the exercise level reco m m e n d e d in behavioral weight loss programs (namely, 1,000 kcal/week) is lower than what should be prescribed. In post hoc analyses, w e (Jeffery et al., 1998) divided subjects into quartiles according to their self-reported physical activity level at 18 months. The top quartile, which reported a m e a n activity level of 2,500 kcal/week, had the best long-term weight loss. Weight losses of the other three quartiles, which reported activity levels of approximately 1,000 kcal/week, did not differ significantly from each other. Similarly, the Jakicic and colleagues (1999) study found that the best weight losses occurred in individuals w h o spent at least 200 minutes/week in physical activity. In the National Weight Control Registry, a registry of individuals w h o have lost at least 13.6 kg (i.e., 30 pounds) and kept h off at least 1 year, successful weight loss maintainers report an average of 2,800 kcal/week of physical activity (Klem, Wing, McGuire, Seagle, & HUI, 1997). Thus a n e w direction being pursued by several investigators is the use of higher exercise goals (2,000-2,500 kcal/week) as a means to promote long-term maintenance of weight loss. The topic of exercise and weight management is further addressed by Blair and Leermakers in Chapter 13 of this volume.
M O T I V A T I O N A L STRATEGIES T O I M P R O V E V^EIGHT L O S S The fact that participants lose weight successfully for approximately 6 months and then begin to experience weight regain has led investigators to begin to focus on ways to help maintain motivation over the long term. In a pUot study on this topic. Smith, Heckemeyer, Kratt, and M a s o n (1997) applied motivational interviewing techniques at three individual sessions during a 16-session behavioral weight control program for patients with Type 2 diabetes. Motivational interviews explored the participants' personal goals, examined the discrepancy between these goals and the participants' current behavior, and acknowledged the ambivalence participants feh about behavior change. The group given motivational interviewing (n = 6) had better adherence to the treatment program (i.e., better attendance, self-monitoring, exercise, and blood sugar monitoring) than those w h o received the stan-
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dard behavioral program (n = 10). Although weight losses were comparable in the two condhions, the motivational interviewing group had better glycemic control following the program. Smith and colleagues are currently conducting a longer study with a larger number of participants to further examine the benefits of motivational interviewing.
Weight Loss Satisfaction Another approach to increasing motivation is to try to increase satisfaction with the weight loss that participants attain during treatment. Unfortunately, most individuals w h o enter weight loss programs desire to lose more weight than typically occurs in these programs, and thus finish treatment feeling dissatisfied. Since most individuals w h o enter weight loss programs are motivated by a desire to improve their health and/or their appearance. Smith, Burke, and W i n g (1999) hypothesized that if treatments were modified to help participants achieve these goals (i.e., better health and/or appearance), participants might be more satisfied with their weight losses. A s reported in an abstract presented at a recent meeting (Smith et al., 1999) found support for this hypothesis. W o m e n (n - 49) were randomly assigned to either a standard behavioral program, a program that stressed physical appearance changes accompaning weight loss, or a program that stressed health changes with weight loss. Persons in the appearance-focused condition lost more weight at 6 months than the standard group (10.4 kg vs. 6.2 kg) and reported greater satisfaction with their overall appearance. Participants in the health-focused condition lost 8.2 kg and reported greater satisfaction with their health improvements than did the standard-condition participants. T h e effect of these approaches on long-term maintenance of weight loss is currently being studied.
Social Support Wing and Jeffery (1999) have tried to improve motivation for long-term weight loss by increasing social support. T w o types of social support were investigated: natural support and experimentally manipulated support. Participants (n - 166) w h o expressed interest in the study were asked to identify three other individuals w h o would like to participate in the study with them. Participants w h o identified three friends were treated together as a "team" and were compared to persons w h o signed up for the program alone (thus this component of the study w a s not randomized). Within both the group of participants recruited with friends and those recruited alone, half of the subjects were then randomly assigned to a standard behavioral treatment program, while the other half were assigned to a weight loss program with social support strategies. These social support strategies included both intragroup team-building activities and intergroup competitions, in which financial incentives were awarded to the team(s) with the best maintenance of weight loss from month 4 to month 10. At both m o n t h 4 and m o n t h 10, participants w h o were recruited with friends had better weight losses than those w h o were recruited alone. However, both the recruitment condition and the social support intervention affected the maintenance of weight loss from month 4 to m o n t h 10. In the group recruited alone and given the standard behavioral treatment (which would represent what is typically done in behavioral weight loss programs), only 2 4 % maintained their weight loss in full over this 6-month follow-up. In contrast, 6 6 % of subjects w h o were recruited with friends and given the social support intervention maintained their weight loss in full. These findings suggest that further attention to social support m a y improve long-term maintenance of weight loss.
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INCREASING THE AUDIENCE FOR WEIGHT CONTROL INTERVENTIONS The studies reviewed above have all utilized a clinical treatment model in which overweight participants are treated in group behavioral weight loss classes. Such approaches have produced the largest weight losses to date. However, an alternative strategy is to try to increase the audience served by weight loss programs, rather than trying to increase the number of kilograms lost by a small number of individuals. T h e use of various types of media, including telephone, television, and Internet, m a y provide greater convenience and anonymity for participants and thereby increase the number of individuals w h o are willing to embark on such weight loss efforts. HeUerstedt and Jeffery (1997) examined the effects of a telephone-based intervenfion. Sixty-four participants were recruited and randomly assigned to a minimal-contact control group or to one of two telephone-based interventions. All three groups attended two initial group meetings and were given basic information about diet, exercise, and self-monitoring, as well as a 6-month supply of food diaries. The control group received no further contact, whereas participants in the phone conditions were called every week for the next 24 weeks and asked to report either their weight or their eating and exercise behavior. Interestingly, the control group lost 5.8 kg over 12 weeks, compared to 3.7 kg for the weight-focused phone group and 3.4 kg for the behaviorally focused phone group. Another surprising finding from this study w a s that the participants w h o signed up for this study appeared similar to those usually seen in face-to-face group programs. Thus it was unclear whether this minimal intervention really accomplished the goal of broadening the population served. Another media approach is to use television broadcasting to deliver the weight loss program. Meyers, Graves, Whelan, and Barclay (1996) compared a standard face-to-face treatment group, a group receiving a face-to-face program that was videotaped for subsequent use, a group that was shown the videotape via television as its treatment contact, and a waiting-hst control. The three treatment groups aU achieved similar weight losses (4.1-4.5 kg over 8 weeks), and differed from the waiting-hst control (0.9 kg). T h e maintenance of weight loss through 15 months also appeared comparable in the group receiving the faceto-face program and the group viewing the T V broadcast. T h e fact that the group that was shown the T V broadcast was weighed before and after the 8 weeks and was asked to send self-monitoring records to the therapist m a y have influenced these outcomes. Similarly, Harvey-Berino (1998) found that weight losses achieved by participants w h o viewed an interactive television program were comparable to those achieved by participants in a face-toface program (7.6 kg vs. 7.9 kg over 12 weeks). Based on these two studies, it appears that further examination of televised programs is warranted. It would be interesting to evaluate the effectiveness of a televised version of a 24-week behavioral program, which is n o w considered the standard length of such programs, and to compare these results to those for a state-of-the-art face-to-face program. Finally, the most recent approach to mediated intervention is the use of Internet interventions and e-mail. Currentiy there are m a n y weight loss W e b sites that provide valuable information about diet and/or exercise, but most do not include the use of standard behavioral procedures, such as self-monitoring or feedback. Tate, Wing, and Winett (2000) developed an Internet-based behavioral weight loss program, which included weekly lessons, prompting for submission of weekly self-monitoring data, personalized feedback on these data, and an online bulletin board for social support. T o test the effectiveness of this Internet intervention, a total of 90 participants (with computer access) were recruited and randomly assigned to Internet Behavior Therapy or Internet Education. Both groups attended
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an initial start-up meeting in which they were taught basic weight control strategies. Those w h o were randomly assigned to Internet Behavior Therapy were then given a 12-week intervention delivered entirely via W e b site and e-mail, with contact only for 3- and 6-month weigh-ins. These participants were sent a n e w behavioral lesson each week; they self-monitored their diet and exercise, and sent these records in weekly via e-mail. Personalized feedback was then provided based on these reports. T h e Internet Education group w a s given access to a W e b site that catalogued and organized available weight-related W e b sites related to diet, exercise, or body weight. However, these participants received none of the behavioral strategies described above. At the end of the 12-week intervention, Internet Behavior Therapy had a m e a n weight loss of 4.1 kg, versus 1.3 kg in Internet Education control group. Thus these low-contact approaches m a y be quite effective for producing initial weight loss.
IMPLICATIONS F O R PRACTICE A N D
RESEARCH
The most effective weight loss programs appear to be those that combine diet, exercise, and behavior modification. This review of the recent literature on such programs suggests that weight loss m a y be improved in the following ways: 1. Use of structured meal plans or portion-controlled diets during initial weeks of the program. 2. Use of home-based or supervised exercise during the initial 6 months of intervention, followed by home-based exercise with continued biweekly therapy contact for months 7-12, and provision of h o m e exercise equipment for long-term maintenance of exercise and weight loss. 3. Use of motivational strategies, such as recruitment with friends and intergroup competition. 4. Development of media-based programs (using telephone, television, or Internet) to increase access to behavioral weight control interventions. Although behaviorists have made tremendous progress in developing weight control programs, a large number of very basic questions remain unanswered. For example, w e still know little about the ideal diet recommendation in terms of either calorie level or macronutrient content. Although thefieldhas typically utilized balanced low-calorie, low-fat diets, there has been little empirical investigation comparing such diets with more extreme low-fat diets (e.g., the Ornish 10%> fat diet), vegetarian diets, or other popular diets (e.g., the Atkins diet). A recent study (Smith, Burke, & Wing, 2000) showed that individuals embarking on a vegetarian diet remained on this diet far longer than individuals starting a diet for weight loss. This difference in duration w a s seen even in subjects w h o had tried both types of diets and was not due to participants' reaching their desired weight loss goal. Interestingly, participants were far more likely to cite boredom as the explanation for stopping their weight loss regimen than for discontinuing the vegetarian diet. These data suggest that teaching patients to maintain variety while on a weight loss diet m a y be helpful (although the poshive results of V L C D s might suggest the opposhe). Similar basic issues remain on the activity side of the energy balance equation. A s noted above, weight loss programs typically recommend 1,000 kcal/week of activity, whereas studies of individuals w h o successfully lose weight suggest that these individuals
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are completing 2,500-2,800 kcal/week of activity. The benefits of these higher levels of physical activity, and of including some higher-intensity activity within the prescription, remain untested. Probably the most consistent finding in the behavioral weight loss literature is the fact that maximal weight loss occurs at about 6 months. This seems to be true in diets of differing calorie levels (and thus appears to be due more to length of time on the diet than to the magnitude of weight loss achieved). T h e reason for this p h e n o m e n o n remains unclear. Researchers have attempted to improve long-term weight loss outcomes by increasing initial weight loss, extending treatment contact, using stronger behavioral techniques, and teaching specific skills related to maintenance (Jeffery et al., 2000). All these approaches have had only modest effects. Further research, examining n e w approaches to the long-term maintenance of weight loss, is clearly needed. For further information on behavioral treatment and weight maintenance, see Perri and Corsica, Chapter 17, this volume. Finally, it is important to explore n e w ways to increase the number of participants in weight loss interventions. Strategies for maintaining the advantages of therapist-led group treatment programs (including accountability, feedback, and group support), while reducing the "costs" of such programs (the need to travel to a given location at a set time during the week, the potential embarrassment), should be examined.
REFERENCES
Andersen, R., Frankowiak, S., Snyder, J., Bartlett, S., & Fontaine, K. (1999). Effects of lifestyl ity vs. structured aerobic exercise in obese women: A randomized trial. Journal of the American Medical Association, 281(4), 335-340. Ditschuneit, H. H., Flechtner-Mors, M., Johnson, T. D., & Adler, G. (1999). Metabolic and weightloss effects of a long-term dietary intervention in obese patients. American Journal of Clinical Nutrition, 69, 198-204. Ferster, C. B, Nurnberger, J. I., Si Levitt, E. B. (1962). The control of eating. Journal of Mathematics, 1, 87-109. Harvey-Berino, J. (1998). Changing health behavior via telecommunications technology: Using interactive television to treat obesity. Behavior Therapy, 29, 505-519. Hellerstedt, W., & Jeffery, R. (1997). The effects of a telephone-based intervention on weight loss. American Journal of Health Promotion, 11, 177-182. Jakicic, J., Wing, R. R., Si Winters, C. (1999). Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, andfitnessin overweight women. Journal of the American Medical Association, 282(16), 1554-1560. Jakick, J. M., Wing, R. R., Butier, B. A., Si Robertson, R. J. (1995). Prescribing exercise in multipk short bouts versus one continuous bout: Effects on adherence, cardiorespiratoryfitness,and weight loss in overweight women. International Journal of Obesity, 19, 893-901. Jeffery, R. W., Drewnowski, A., Epstein, L., Stunkard, A. J., WiUson, G., Wing, R. R., & Hill, R. (2000). Long-term maintenance of weight loss: Current status. Health Psychology, 19(1), 5-16. Jeffery, R W., Wing, R. R., Thorson, C , Sc Burton, L. C. (1998). Use of personal trainers and financial incentives to increase exercise in a behavioral weight-loss program. Journal of Consulting and Clinical Psychology, 66, 777-783. Klem, M . L., Wing, R. R., McGuhe, M . T., Seagk, H. M., & HiU, J. O. (1997). A descriptive study of individuals successful at long-term maintenance of substantial weight loss. American Journal of Clinical Nutrition, 66, 239-246. Meyers, A., Graves, T., Whelan, J., Sc Barclay, D. (1996). A n evaluation of a television-delivered behavioral weight loss program: Are the ratings acceptable? Journal of Consulting and Clinical Psychology, 64, 172-178.
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National Heart, Lung, and Blood Institute (NHLBI). (1998). Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in aduhs: The evidence report. Obesity Research, 6(Suppl.), 51S-210S. Perti, M . G., Martin, A. D., Leermakers, E. A., Sears, S. F., & Notelovitz, M . (1997). Effects of group- versus home-based exercise in the treatment of obesity. Journal of Consulting and Clinical Psychology, 65, 278-285. Pronk, N . P., & Wing, R. R. (1994). Physical activity and long-term maintenance of weight loss. Obesity Research, 2, 587-599. Skender, M . S., Goodrkk, G. K., Deljungo, D. J., Reeves, R. S., Darnell, L., Gotto, A. M., Sc Foreyt, J. P. (1996). Comparison of 2-year weight loss trends in behavioral treatments of obesity: Diet, exercise, and combination interventions. Journal of the American Dietetic Association, 96, 342-346. Smith, C , Burke, L., & Wing, R. R. (1999). 6-month outcome of two behavioral weight loss treatments focusing on primary motivations for weight loss [Abstract]. Obesity Research, 7, 19S. Smith, C , Burke, L., Si Wing, R. R. (2000). Vegetarian and weight loss diets among young adults. Obesity Research, 8(1), 123-129. Smith, D., Heckemeyer, C , Kratt, P., Si Mason, D. (1997). Motivational interviewing to improve adherence to a behavioral weight-control program for older obese w o m e n with N I D D M . Diabetes Care, 20(1), 52-58. Stuart, R. B. (1967). Behavioural control of overeating. Behavioural Research and Therapy, 5, 357-365. Tate, D., Wing, R. R., & Winett, R. (2001). Development and evaluation of an Internet behavior therapy program for weight loss. Journal of the American Medical Association, 285, 1172-1177. Wadden, T. A. (1993). The treatment of obesity: A n overview. In A. J. Stunkard Si T. A. W a d d e n (Eds.), Obesity: Theory and therapy (2nd ed., pp. 197-218). N e w York: Raven Press. Wadden, T. A., Foster, G. D., & Letizia, K. A. (1994). One-year behavioral treatment of obesity: Comparison of moderate and severe caloric restriction and the effects of weight maintenance therapy. Journal of Consulting and Clinical Psychology, 62, 165-171. Wadden, T. A., & Stunkard, A. J. (1986). Controlled trial of very low calorie diet, behavior therapy, and their combination in the treatment of obesity. Journal of Consulting and Clinical Psychology, 54, 482-488. Wadden, T. A., Stunkard, A. J., & BrowneU, K. D. (1983). Very low calorie diets: Their efficacy, safety, and future. Annals of Internal Medicine, 99, 675-684. Wadden, T. A., Vogt, R. A., Andersen, R. £., Bartiett, S. J., Foster, G. D., Kuehnel, R. H., Wilk, J., Weinstock, R., Buckenmeyer, P., Berkowitz, R. I., Si Steen, S. N . (1997). Exercise in the treatment of obesity: Effects of four interventions on body composition, resting energy expenditure, appetite, and mood. Journal of Consulting and Clinical Psychology, 65, 269-277. Wadden, T. A., Vogt, R. A., Foster, G. D., Si Anderson, D. A. (1998). Exercise and maintenance of weight loss: 1-year foUow-up of a controlled clinic trial. Journal of Consulting and Clinical Psychology, 66(1), 429-433. Wing, R. R. (1998). Behavioral approaches to the treatment of obesity. In G. Bray, C. Bouchard, & W . P. T. James (Eds.), Handbook of obesity (pp. 855-873). N e w York: Marcel Dekker. Wing, R. R. (1999). Physical activity in the treatment of the adulthood overweight and obesity: Current evidence and research issues. Medicine and Science in Sports and Exercise, 31(11), S547-S552. Wing, R. R., Blah, E., Marcus, M., Epstein, L. H., Sc Harvey, J. (1994). Year-long weight loss treatment for obese patients with Type II diabetes: Does inclusion of an intermittent very low calorie diet improve outcome? American Journal of Medicine, 97, 354-362. Wing, R. R., Si Jeffery, R. W . (1979). Outpatient treatments of obesity: A comparison of methodology and clinical results. International Journal of Obesity, 3,161-179. Wing, R. R., & Jeffery, R. W . (1999). Benefits of recruiting participants with friends and increasing social support for weight loss maintenance. Journal of Consulting and Clinical Psychology, 67(1), 132-138. Wing, R. R., Jeffery, R. W., Burton, L. R., Thorson, C , Sperber Nissinoff, K., Si Baxter, J. E. (1996).
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Food provision vs. structured meal plans in the behavioral treatment of obesity. International Journal of Obesity, 20, 56-62. Wing, R. R., Marcus, M . D., Salata, R., Epstein, L. H., Miaskiewicz, S., Si Blah, E. H. (1991). Effects of a very-low-calorie diet on long-term glycemic control in obese Type 2 diabetic subjects. Archives of Internal Medicine, 151, 1334-1340. Wing, R. R., Venditti, E. M., Jakicic, J. M., PoUey, B. A., Si Lang, W . (1998). Lifestyk intervention in overweight individuals with a family history of diabetes. Diabetes Care, 21(3), 350-359.
1
D r u g
5
Treatment
of
Obesity
G E O R G E A. BRAY
Drug treatment for obesity has been tarnished by a number of disasters (Bray, 1998a). Since 1893, almost any drug treatment that has been used in obese patients has generated undesirable outcomes that have resulted in their termination. Table 15.1 is a historical presentation of drug treatments for obesity and the disasters that befell them. A n additional serious negative impact on the use of drug treatment for obesity is the negative halo spread by the addictive properties of amphetamine (Bray, 1993, 1998b; Bray, Atkinson, & Inoue, 1995; Bray & Greenway, 1999; Bray & Inoue, 1992). Amphetamine, or a-methyl-|3-phenethylamine, is an addictive p-phenethylamine that reduces food intake. The addictiveness of dextroamphetamine is probably related to its effects on dopaminergic neurotransmission. Its anorectic effects, on the other hand, are probably due to its modulation of noradrenergic neurotransmission. Because this p-phenethylamine w a s addictive, other P-phenethylamine derivatives were presumed to be addictive. Whether actually addictive or not, they were presumed guilty by association. This has led to restrictions on the use of this entire class of drugs by the U.S. Drug Enforcement Agency ( D E A ) (Bray, 1993, 1998a; Bray & Greenway, 1999). Appetite-suppressing drugs such as phentermine, diethylpropion, fenfluramine, and sibutramine, and the antidepressant venlafaxine, are all p-phenethylamines (Bray & Greenway, 1999). Phentermine and diethylpropion are sympathomimetic amines like amphetamine, but differ from amphetamine in having littie or no effect on dopamine release at the synapse. Abuse of either phentermine or diethylpropion is rare. Fenfluramine, on the other hand, has no effect on reuptake or release of either norepinephrine (NE) or dopamine in the brain, but increases serotonin release and partially inhibits serotonin reuptake. Thus the derivatives of p-phenethylamine have a wide range of pharmacological effects. However, if examined uncritically, they could all be lumped with amphetamine and carry its negative halo (Bray et al., 1995). It is thus misleading to use "amphetamine-like" in reference to appethe-suppressant p-phenethylamine drugs except amphetamine and methamphetamine, because of the negative Unguistic images. A third issue in drug treatment of obesity is the perception that because patients regain weight w h e n drugs are stopped, the drugs are ineffective (Bray, 1998b; Bray et al., 1995). 317
318
TREATMENT O F ADULT OBESITY
TABLE 15.1. Disasters with Drug Treatments for Obesity Date
Drug
Outcome
1893 1934 1937 1967 1971 1997
Thyroid Dinitrophenol Amphetamine Rainbow pills (digitahs, diuretics) Aminorex Fenfluramine ± phentermine Dexfenfluramine ± phentermine
Hyperthyroidism Cataracts, neuropathy Addiction Deaths Pulmonary hypertension Valvular insufficiency
Quite the contrary is true. Overweight is a chronic disease that has m a n y causes. Cure is rare, however, and treatment is thus aimed at paUiation. A s clinicians, w e do not expect to cure with medications such diseases as hypertension or hypercholesterolemia. Rather, w e expect to palliate them. W h e n the medications for any of these diseases are discontinued, w e expect the disease to recur. This means that medications only w o r k w h e n used. The same arguments go for medications used to treat overweight: It is a chronic, incurable disease for which drugs only w o r k w h e n used. Recent reports of valvular heart disease associated with the use of fenfluramine, dexfenfluramine, and phentermine have provided the most recent problem for drug treatment of obesity (Connolly et al., 1997; R y a n et al., 1999). This is an example of the "law of unintended consequences." T h e report of valvulopathy in up to 3 5 % of patients treated with the combination of fenfluramine and phentermine w a s totally unexpected. The finding, however, will add caution to the marketing of any future drugs to treat obesity, and will provide support for those w h o believe that drug treatment of obesity is inappropriate.
M E C H A N I S M S F O R D R U G EFFECTS IN T R E A T M E N T O F OBESITY Corpulence results from an imbalance between energy intake and energy expendhure (Bray, 1998b). This relationship can be described with a nutrient balance-feedback model (Figure 15.1). The targets in this model where drugs might be used are shown as shaded boxes in Figure 15.1. The nutrient balance-feedback model provides the framework for this approach to drug treatment. Drugs can reduce food intake, alter metabolism, and/or increase energy expenditure. This framework is used in discussing the available and potential drug leads for treatment of obesity. Reduction of Food Intake Noradrenergic Receptors A number of monoamines and neuropeptides are known to modulate food intake (Bray, 1993; Bray & Greenway, 1999). Both noradrenergic receptors and serotonergic receptors have served as the sites for clinically useful drugs to decrease food intake (Table 15.2). Activation of the a^ or p, adrenoceptors decreases food intake. Stimulation of the Wi adrenoceptor in experimental animals, on the other hand, increases food intake. Direct agonists and drugs that release N E or block N E reuptake can activate one or more of these receptors, depending on where the N E is released. Phenylpropanolamine (PPA) is an aj agonist that decreases food intake by acting on aj-adrenergic receptors in the paraventricular
Drug Treatment of Obesity Weight Change
_
319
Total E n e r g y
Total E n e r g y
intake
Expenditure
Eating
Physical Activity
Thermic Effect
Basal Energy
of Food
Targets of Behavior Therapy F I G U R E 15.1. Targets for drug treatment in an energy balance model.
nucleus. T h e weight gain seen in patients treated for hypertension or prostatic hypertrophy with aj-adrenergic antagonists indicates that the aj adrenoceptor is clinically important in regulation of body weight in h u m a n beings. Stimulation of the P2 adrenoceptor by N E or agonists like terbutaline, clenbuterol, or salbutamol reduces food intake. T h e small weight gain in patients treated with s o m e P2-adrenergic antagonists also indicates that this is a clinically important receptor for regulation of body weight.
Serotonergic Receptors The serotonin receptor system, which consists of seven families of receptors, is also involved in modulating food intake (Baez, Kursar, Helton, Wainscott, & Nelson, 1995). Stimulation of receptors in the 5-HTi a n d 5 - H T 2 families have the major effects o n feeding. Activation of 5-HTiA receptors increases food intake, but this acute effect is rapidly down-regulated and is not clinically significant in regulation of body weight. Activation of the 5-HT2C and
T A B L E 15.2. Monoamine Mechanisms that Reduce Food Intake Neurotransmitter system
Mechanism of action
Examples
Noradrenergic
«! agonist P2 agonist Stimulates N E release Blocks N E reuptake 5-HTip or 5-HT2C agonists Stimulates 5-HT release Blocks 5-HT reuptake Di agonist Hi antagonist
Phenylpropanolamine (PPA) Clenbuterol Phentermine Mazindol Quipazine Fenfluramine Fluoxetine Bromocriptine Chlorpheniramine
Serotonergic
Dopaminergic Histaminergic
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TREATMENT O F ADULT OBESITY
possibly 5-HTiB receptors decreases food intake (Bray & Greenway, 1999). Direct agonists (quipazine) or drugs that block serotonin reuptake will reduce food intake by acting on these receptors or by providing the serotonin that modulates these receptors.
Altered Metabolism Excess fat is the visible sign of obesity. Metabolic strategies have been directed to preabsorptive and postabsorptive mechanisms (Bray, 1998b). Preabsorptive mechanisms that influence digestion and absorption of macronutrients are used by orlistat, which inhibits intestinal digestion of fat and lowers body weight. The second strategy is to affect intermediary metabolism. Enhancing lipolysis, inhibiting lipogenesis, and affecting fat distribution between subcutaneous and visceral sites are strategies that can be developed.
Increased Energy Expenditure Increased energy expenditure through exercise would be an ideal approach to treating obesity. Drugs with the same physiological consequences as exercise would provide useful ways of treating obesity.
D R U G S T H A T R E D U C E F O O D INTAKE Table 15.3 summarizes the effects of a number of drugs that treat obesity by reducing food intake. They are discussed in more detail below.
Noradrenergic Drugs Approved for Short-Term Treatment of Obesity The noradrenergic drugs are grouped together because they can increase blood pressure and, in part, act like the neurotransmitter N E . Drugs in this group work by a variety of mechanisms, including the release of N E from synaptic granules (benzphetamine, phendimetrazine, phentermine, and diethylpropion); blockade of N E reuptake (mazindol); blockade of reuptake of both N E and serotonin (sibutramine); or direct action on adrenoceptors (PPA) (Table 15.2). All of these drugs are absorbed orally and reach peak blood concentrations within 1-2 hours (Bray & Greenway, 1999). The half-hfe in blood is short for aU except the metabolites of sibutramine, which have a long half-life. Both metabolites of sibutramine are active, but this is not true of the other drugs in this group. Liver metabolism inactivates a large fraction of these drugs before excretion. Side effects include dry mouth, constipation, and insomnia. Food intake is suppressed either by delaying the onset of a meal or by producing early satiety. Sibutramine and mazindol have both been shown to increase thermogenesis experimentally. The efficacy of an appetite-suppressing drug can be established by showing in doubleblind randomized clinical trials that h produces a significantly greater weight loss than a placebo drug (Bray & Greenway, 1999), and that this weight loss is more than 5 % below baseline weight. A n alternative criterion is that a significantly greater proportion of drugtreated patients than placebo-treated patients lose more than 5 % or more than 1 0 % of baseline weight (Bray et al., 1995). Chnical trials of sympathomimetic drugs done before 1975 were generally short term, because it was widely beheved that short-term treatment would "cure obesity" (Bray, 1993; Bray & Greenway, 1999). This was unfounded opti-
T A B L E 15.3. Drugs That Reduce Food Intake
Drug group
FDA approval
Approved duration of treatment
DEA schedule
Trade names
Dosage form (mg)
Administration
Sympathomimetic drugs approved for short-term use Diethylpropion
Yes
Few weeks
IV
Tenuate Tenuate, Dospan
25 75
25 mg, threetimesdaily 75 mg, once daily
Phentermine
Yes
Few weeks
IV
Standard: Adipex-P Duromine Fastin Obenix Oby-Cap Oby-Trim Zantryl
37.5 30 37.5 30 30 30
37.5 mg, in a.m. 30 mg/day, 2 hr after breakfast 37.5 mg/day, 9 a.m. 30 mg/day, 2 hr after breakfast 30 mg/day, 2 hr after breakfast 30 mg/day, 2 hr after breakfast
CO
15,30
15 mg/day, before breakfast (30 m g for less responsive patients)
Slow-release: loamin Sympathomimetic drug approved for long-term use Serotonin-norepinephrine reuptake inhibitor Sibutramine
Yes
Long-term
IV
Meridia
5, 10, 15
Initial dose: 10 mg/day M a x i m u m dose: 15 mg/day
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TREATMENT O F ADULT OBESITY
mism, but because the trials were of short duration and were often crossover in design, they provided few long-term data. This discussion focuses on longer-term trials lasting over 24 weeks, and on those trials in which there was an adequate control group.
Phentermine and Diethylpropion A 36-week trial comparing continuous administration of phentermine with intermittent phentermine and placebo is shown in Figure 15.2 (Munro, MacCuish, Wilson, & Duncan, 1968). Both continuous and intermittent phentermine therapy produced more weight loss than the placebo. In the drug-free periods, weight loss slowed only for the intermittently treated patients; then the patients would lose weight more rapidly w h e n the drug was reinitiated. A small trial with diethylpropion showed greater weight loss than with placebo (Bray & Greenway, 1999). Phentermine and diethylpropion are Schedule IV drugs in the D E A regulatory classification, indicating the potential for abuse, although the potential appears to be very low. Phentermine and diethylpropion are only approved for a few weeks, which is widely interpreted as up to 12 weeks in any calendar year. Weight loss with phentermine and diethylpropion persists for the duration of treatment, suggesting that tolerance does not develop to these drugs. If tolerance does develop, the drugs would be expected to lose their effectiveness or require increased amounts of drug for patients to maintain weight loss. This does not seem to occur.
/Vlazindol There are no long-term, double-blind, placebo-controlled, parallel-arm studies with mazindol, but there are two open-label studies that deserve comment. Enzi, Baritussio, Marchiori, and Crepaldi (1976) studied 102 patients on mazindol (2 mg/day) and 102 patients on
(A If) m o U) "5
T i m e in Weel<s FIGURE 15.2. Comparison of weight loss with continuous and intermittent therapy with phentermine. From Mason and Ito (1969). Copyright 1969 by Annals of Surgery. Adapted by permission.
Drug Treatment of Obesity
323
placebo in a 15-week trial using a crossover design, with an additional 12 months of treatment with mazindol. There w a s no significant difference between the drug and placebo conditions during the 15-week controlled trial, but mazindol produced significantly more weight loss during the long-term (15-month) period of treatment. In a 12-month open-label study of mazindol in Japan, Inoue (1995) enrolled 32 subjects, half of w h o m dropped out prior to 1 year of treatment. In a last-observation-carriedforward analysis, there was a 9 % loss of initial body weight, which is comparable to that produced by several other weight loss medications. Blood pressure, glucose, insuhn, cholesterol, triglycerides, and alanine transaminase levels declined during treatment.
Phenylpropanolamine PPA is an ai-adrenergic agonist of the propanolamine group. It is an over-the-counter preparation with a provisional F D A approval for weight loss. In reviews by Weintraub (1985) and Greenway (1992), including published and unpubhshed studies obtained from the manufacturer, 1,439 subjects were on active medication and 1,086 on placebo. At the end of the studies, which were up to 12 weeks in length and performed before 1985, subjects on P P A lost about 0.27 kg/week more than the subjects on placebo. T o date, there is only one controlled trial of P P A that has lasted 20 weeks. In this double-blind placebo-controlled trial, 101 subjects were treated with placebo or P P A for 6 weeks, with an optional double-blind extension to week 20 (Schteingart, 1992). At 6 weeks, the PPA-treated group had lost 2.4 kg (0.43 kg/week), compared to 1.1 kg (0.18 kg/week) in the placebo group. In the optional extension, 24 subjects on P P A lost 5.1 kg (6.5%), compared to 12 subjects treated with placebo w h o lost 0.4 kg/week (0.5%) of initial body weight ip < .05).
Sympathomimetic Drugs Approved for Long-Term Use Sibutramine In experimental animals, the inhibition of food intake by sibutramine is duplicated by combining a noradrenergic reuptake inhibitor (nisoxetine) with a serotonin reuptake inhibitor (fluoxetine) (Ryan, Kaiser, & Bray, 1995). Sibutramine produces the behavioral sequence of satiety (Halford, Heal, & Blundell, 1994). Sibutramine does not bind to any of a wide variety of receptors on which it has been tested. In addition to the inhibition of food intake (RoUs, Shide, Thorwart, & Ulbrecht, 1998), sibutramine stimulates thermogenesis in experimental animals (Stock, 1997). The h u m a n data on thermogenesis are contradictory (Hansen, Toubro, Stock, Macdonald, &C Astrup, 1998; Seagle, Bessesen, & HUI, 1998). Both short-term (Hanotin, T h o m a s , Jones, Leutenegger, & Drouin, 1998; Lean, 1997; Weintraub, Rubio, Golik, Byrne, & Scheinbaum, 1991) and long-term (Apfelbaum et al., 1999; Bray et al., 1996, 1999; Jones, Smith, Kelly, & Gray, 1995) clinical trials have been reported with sibutramine. In an 8-week trial comparing placebo with 5 and 20 mg/day of sibutramine, Weintraub and colleagues (1991) noted a weight loss of 1.4 ± 2.1 kg in the placebo group, 2.9 ± 2.3 kg in the group treated with 5 mg/day and 5.0 ± 2.7 kg in the group treated with 20 mg/day. In a multicenter dose-ranging trial (Bray et al., 1996, 1999), sibutramine produced a dose-related weight loss lasting up to 6 months (Figure 15.3). A total of 1,043 patients were randomly assigned to receive placebo or 1, 5, 10, 15, 20, or 30 mg/day of sibutramine. There was a clear dose response, with the placebo group losing 1 % and the 30-mg/day group losing 9.5% of initial body weight. By the end of the 6 months, patients receiving the
TREATMENT OF ADULT OBESITY
324
End Of Treatment
s: D) c c n 4 • A • • 0 A
c ra 0)
Placebo 1 mg 5mg 10 mg 15 mg 20 mg 30 mg
-10 12
16
20
24
24
27
30
Treatment Weel< FIGURE 15.3. Effect of sibutramine on body weight. There was a dose-dependent reduction in body weight over the 24 weeks of the trial. From Bray et al. (1999). Copyright 1999 by Obesity Research. Adapted by permission.
lower doses had plateaued in their weight loss, but the groups receiving 15, 20, and 30 mg/day were still losing weight. There have been two 1-year trials with sibutramine (Apfelbaum et al., 1999; Jones et al., 1995). In one trial, reported only in abstract form, doses of 10 and 15 mg/day of sibutramine were compared with placebo (Jones et al., 1995). A total of 463 patients began the trial, and 259 completed it. A m o n g those completing the trial, those in the placebo group lost 2.4 kg, compared with 6.2 kg, in those receiving 10 mg/day and 6.9 kg in the group receiving 15 mg/day (Jones et al., 1995). In the second study, patients w h o lost at least 6 kg during a 4-week period on a very-low-energy diet were randomly assigned to a double-blind controUed trial comparing placebo and 10 mg/day of sibutramine (Apfelbaum et al., 1999). O f the 78 patients in the placebo group, 48 completed 1 year of treatment and essentially maintained their weight loss, weighing 7.6 kg less than at baseline. In the group treated with sibutramine (10 mg/day), weight loss w a s further increased to 13.5 kg below baseline (Apfelbaum et al., 1999). The Sibutramine Trial of Obesity Reduction Maintenance w a s a double-blind randomized comparison of sibutramine (10 mg/day) versus placebo following 6 months of weight loss induced by sibutramine. During the initial weight loss period, the diet assignment was based on estimates of resting energy expenditure, and w a s readjusted at the third month. At the end of 6 months, the body weight w a s reduced by nearly 1 5 % . During the next 18 months of treatment in the randomized trial, the subjects in the sibutramine treatment group maintained most of their body weight loss, whereas the group assigned to placebo showed a steady regain in weight (James et al., 2000). Thus sibu-
Drug Treatment of Obesity
325
tramine appears to be useful for both weight loss and maintenance of weight loss, or secondary prevention. A n analysis of the effect of sibutramine on changes in lipids was done by combining data from 11 trials. There were significant dose-related reductions in triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol (Bray et al., 1999). Sibutramine raises blood pressure slightly (as discussed below). Initial weight loss in patients treated with sibutramine predicts long-term response. O f those losing >2 kg in 4 weeks, only 2 0 % of those on placebo versus 4 9 % of those on sibutramine lost more than 1 0 % of initial body weight in 12 months (Bray et al., 1996). Sibutramine is approved for weight loss and the maintenance of weight loss in the United States. It has not been associated with valvulopathy.
Safety of Noradrenergic/Sympathomimetic Drugs The side effect profile for sympathomimetic drugs is similar. They mainly produce insomnia, dry mouth, asthenia, and constipation. The safety of older sympathomimetic appetitesuppressant drugs has been the subject of considerable controversy, because dextro-amphetamine is addictive (Bray & Greenway, 1999). The other sympathomimetic drugs—phentermine, diethylpropion, and mazindol—have very little abuse potential, as assessed by the low rate of reinforcement w h e n the drugs are available intravenously to test animals. In this same paradigm, neither P P A nor fenfluramine showed any reinforcing effects, and no clinical data revealed any abuse potential for either of these drugs. Sibutramine likewise has no abuse potential in this paradigm, but it is nonetheless a Schedule IV drug (Heal et al., 1992). Sympathomimetic drugs can affect blood pressure (Bray & Greenway, 1999). P P A is an ttj agonist and, at doses of 75 m g or more, can increase blood pressure. Phenylpropanolamine has been associated with stroke and it should not be used above 75 mg/day. PPA has also been reported in association with cardiomyopathy. In the placebo-controlled studies with sibutramine, systolic and diastolic blood pressure increased by 1-3 m m H g , and pulse increased by approximately 4-5 beats per minute (Bray et al., 1999). Caution should be used in combining sibutramine with other drugs that m a y increase blood pressure. Sibutramine should not be used in patients with a history of coronary artery disease, congestive heart failure, cardiac arrhythmias, or stroke. There should be a 2-week interval between terminating monoamine oxidase inhibitors ( M A O I s ) and beginning sibutramine, and sibutramine should not be used with M A O I s or selective serotonin reuptake inhibitors. Because sibutramine is metabolized by the cytochrome P450 enzyme system (isozyme C Y P 3 A 4 ) , it m a y interfere with metabolism of erythromycin and ketoconazole.
Peptides That Reduce Food Intake Leptin Leptin is a peptide produced primarily in adipose tissue (Mantazoros, 1999). Absence of leptin produces massive obesity in mice (ob/ob) and in h u m a n s (Montague et al., 1997). Treatment with the peptide decreases food intake in the ob/ob mouse and in leptin-deficient human beings. The diabetes mouse (db/db) and the fatty rat (fa/fa) that have genetic defects in the leptin receptor are also obese, but they do not respond to leptin. H u m a n s with defects in the leptin receptor are also obese (Bray & Tartaglia, 2000). Leptin levels in the blood are highly correlated with body fat levels, yet obesity persists, suggesting that there m a y be "leptin resistance." A n initial clinical trial with leptin showed that it reduced food intake in
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a leptin-deficient human being (Farooqi et al., 1999). In a small dose-ranging study, leptin injections modestly reduced body weight at the highest dose and produced local irritation at the injection site (Heymsfield et al., 1999). Neuropeptide Y Neuropeptide Y (NPY) is one of the most potent stimulators of food intake and appears to act through Y I or Y 5 receptors (Kalra et al., 1999). Antagonists to this receptor m a y block N P Y and thus decrease feeding. Early trials of one antagonist to the N P Y receptor are underway, and more are expected soon. Cholecystokinin Cholecystokinin ( C C K ) reduces food intake in h u m a n beings and experimental animals (Smith, 1998). This effect does not require an intact hypothalamic feeding control system, but does appear to require an intact vagus nerve. Peptide analogues have been developed and tested experimentally, but clinical data have not yet been published. A second strategy to modify C C K activity is to reduce the degradation of C C K . This approach is likewise under evaluation. Pancreatic Fiormones Pancreatic glucagon produces a dose-related decrease in food intake. A fragment of glucagon (amino acids 6-29) called glucagon-like peptide-1 reduced food intake w h e n given either peripherally in humans (Flint, Raben, Astrup, & Hoist, 1998) or into the brains of experimental animals. Chronic subcutaneous infusion for 2 weeks in patients with diabetes reduced food intake (GutzwUler et al., 1999). Intensive insulin treatment or use of insulin secretagogues (sulfonylureas) increases body weight more than conventional treatment (U.K. Prospective Diabetes Study Group, 1998). Blockade of insulin release using octreotide in obese children with hypothalamic obesity has been reported to reduce weight gain (Lustig et al., 1999).
D R U G S T H A T ALTER M E T A B O L I S M Preabsorptive Agent: Orlistat Orlistat is a potent inhibitor of most, if not aU, mammalian lipases (Bray & Greenway, 1999; Bray & Tartagha, 2000; Guerciolini, 1997; Lockene, Skottova, & Olivecrona, 1994). During short-term treatment with orlistat, fecal fat loss rises during the days of treatment and then returns to control levels after the medication is discontinued, as would be expected from an inhibitor of intestinal lipase (Hauptman, Jeunet, & Hartmann, 1992; Zhi et al., 1994,1996). With volunteers eating a 3 0 % fat diet, there is a dose-related increase in fecal fat loss, which increases rapidly with doses up to 200 mg/day and then reaches a plateau with doses above 400-600 mg/day (Hauptman et al., 1992). Because of its lipid solubility, less than 1 % of an oral dose is absorbed and degraded into two major metabolites (Melia et al., 1995). Clinical studies suggest that orlistat does not affect the pharmacokinetic properties of digoxin (Zhi, M e h a , Koss-Twardy, et al, 1995), phenytoin (Zhi, Melia, Koss-Twardy, et al., 1995), warfarin (Guzelhan, Odink, Niestijl Jansen-Zuidema, & Hartmann, 1994), glyburide (Guzelhan et al., 1994), oral contraceptives (Weber, T a m , Schmidtke-Schrezenmeier, Jonkmann, & van Brummelen, 1996), or alcohol (Guerciolini, 1997). Orlistat also did not affect a single dose
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of four different antihypertensive drugs: furosemide, captopril, nifedipine (U.K. Prospective Diabetes Study Group, 1998), or atenolol (Lockene et al, 1994). Absorption of vitamin A, E, and p-carotene m a y be slightly reduced (GutzwUler et al., 1999), and this m a y require vhamin therapy in a small number of patients.
Weight Loss with Orlistat Several double-bhnd, randomized, placebo-controlled trials with oriistat lasting 1 and 2 years have been reported (Bray &c Greenway, 1999; Davidson et al., 1999; Hauptman, Guerciolini, & Nicholas, 1999; HiU et al, 1999; Hollander et al., 1998; Sjostrom et al, 1998). The design of the trials lasting 2 years followed two formats. They all included a 4- to 5-week singleblind run-in period, after which subjects were stratified into those losing > 2 kg or <2 kg. Orlistat was given at a dose of 60 or 120 m g before each of three meals. The diet contained 3 0 % fat, and during the first year it was designed to produce a mild hypocaloric deficit of 500-600 kcal/day. During the second year, patients were placed on a "eucaloric" diet to evaluate the effect of orlistat on weight maintenance. Weight loss at 2 years varied from 5 . 5 % to 6.6% of initial body weight in the placebo group and from 8.5% to 1 0 . 2 % in the orlistattreated group. During the second year, patients were kept on the same drug regimen as in the first year in two trials (Hauptman et al., 1999); in the other two trials (Davidson et al., 1999; Sjostrom et al., 1998), patients were randomly reassigned to placebo or active drug in a crossover design. The percentage of patients losing > 5 % ranged from 2 3 % to 4 9 . 2 % in the placebo-treated group and from 4 9 % to 6 8 . 5 % in those treated with orlistat. W h e n a criterion of > 1 0 % weight loss was used, 1 7 . 7 % to 2 5 % of placebo-treated patients reached this goal, compared to the more successful 3 8 . 8 % to 4 3 % a m o n g those treated with orlistat. Nearly two-thirds of the enrolled patients completed year 1. Data on the second year of treatment are available from three studies. In one study, subjects remained on the same treatment for 2 years (Hauptman et al., 1999). At the end of the second year, weight loss from baseline was 7.6% ± 7 . 0 % for those on orhstat, compared to 4.5% ± 7.6% in the placebo group. At 1 year the corresponding losses were 9.7 + 6.3% and 6.6 ± 6.8%. In the two other studies, the orlistat subjects were randomly reassigned at the end of 1 year to placebo or orhstat (60 or 120 m g , three times a day) (Davidson et al., 1999; Sjostrom et al., 1998). O n e of these is shown in Figure 15.4 (Sjostrom et al., 1998). Those remaining on orlistat for 2 years regained 3 2 . 5 % from the end of year 1 to the end of year 2, but were stiU 8.8 ± 7.6% below baseline. Patients w h o continued on orlistat with the maintenance diet regained half as m u c h (2.5 kg, or 2.6%) as those switched from orlistat to placebo (5.7 kg, or 5 2 % regain). In this trial, subjects w h o received orlistat in the second year and placebo in the first lost an average of 0.9 kg more. These data show that initial weight loss is greater on orlistat, and that weight regain is slowed by orlistat. The 2-year Prevention of Weight Regain Study treated patients, w h o had lost more than 8 % of their initial weight by dieting, with oriistat (i.e., 30, 60, or 120 m g , three times a day) (HiU et al., 1999). At the end of 1 year the placebo-treated group had regained 5 6 % of the weight they had lost, in contrast with a regain of 3 2 . 4 % in the group treated with orlistat (120 m g , three times a day).
Changes in Lipids Orlistat improves some serum lipid values more than can be explained with weight reduction alone (Bray & Greenway, 1999; Davidson et al., 1999; Reitsma, Castro Cabezas, de Bruin, & Erkelens, 1994; Sjostrom et al, 1998; Tonstad et al., 1994). In a multicenter trial, Tonstad and colleagues (1994) compared oriistat at 30-360 mg/day with placebo on a
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FIGURE 15.4. Orlistat and body weight. From Sjostrom et al. (1998). Copyright 1998 by The Lan Ltd. Adapted by permission.
weight-maintaining diet in an 8-week, double-blind, randomized trial. Total cholesterol and L D L cholesterol were reduced 4 % - l l % and 5 % - 1 0 % , respectively, in the orlistat groups compared to the placebo group (Tonstad et al., 1994). This reduction in cholesterol is probably related to the solubility of cholesterol in the fat lost in the feces as a result of taking orlistat. This fecal loss may necessitate supplementation with fat-soluble vitamins during treatment, because they m a y also be lost. During the weight loss period, there was a decline in total cholesterol, L D L cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glucose, and blood pressure. Reitsma and colleagues (1994) reported that postprandial lipemia was reduced. Orlistat appears to reduce cholesterol, but not glucose or blood pressure, by more than can be accounted for by the decrease in body weight. Changes in Glycemic Control
In a 1-year trial in patients with diabetes (HoUander et al., 1998), the orlistat-treated patients lost 6.2% and the placebo-treated patients 4.3% of their initial weight. There was also a reduction in the need for hypoglycemic medication. Side Effects
The side effects of orlistat are to be expected from its mechanism of action on pancreatic l pase (Canovatchel, 1997; Zhi, Melia, Eggers, Joly, & Patel, 1995). These include intestinal
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borborygmi, flatus, and abdominal cramps. The most troubling effects were fecal incontinence, oily spotting, and flatus with discharge. In a comparison of pooled data on 1,740 placebo-treated and 2,038 orUstat-treated patients, orhstat appeared to be well tolerated, with the principal complaints being gastrointestinal symptoms. M o s t were mild and occurred within the first few weeks (Canovatchel, 1997). M o r e placebo-treated patients (35%) withdrew prematurely than orlistat-treated patients ( 2 9 % ) . There was no evidence for gallstones, renal stones, or cardiovascular or central nervous system events. Orlistat has been approved worldwide for weight loss and the maintenance of weight loss.
Postabsorptive Drugs Metformin Metformin is a biguanide that is approved for the treatment of diabetes mellitus, a disease that is exacerbated by obesity and weight gain. Metformin has been associated with significant weight loss w h e n compared to sulfonylureas or placebo (Bray SiC Greenway, 1999). CampbeU, Menzies, Chalmers, McBain, and B r o w n (1994) compared metformin and glipizide in a randomized double-blind study of individuals with Type 2 diabetes w h o had not achieved control of their disease on diet. The 2 4 subjects on metformin lost weight and had better control of fasting glucose and glycohemoglobin than the glipizide group. The glipizide group gained weight, and the difference in weight between the two groups at the end of the study was highly significant. In a double-blind placebo-controlled trial in subjects with the insulin resistance syndrome, metformin also increased weight loss. Fontbonne and colleagues (1996) reported the results from the B I G P R O study, a 1year French multicenter study that compared metformin with placebo in 324 middle-aged subjects with upper-body obesity and the insulin resistance syndrome. The subjects on metformin lost significantly more weight (1-2 kg) than the placebo group, and the study concluded that metformin m a y have a role in the primary prevention of Type 2 diabetes. The package insert for metformin describes a 29-week double-blind study comparing glyburide (20 mg/day) with metformin (2.5 g/day) and their combination in 632 subjects with Type 2 diabetes w h o had inadequate glucose control. The metformin group lost 3.8 kg, compared to a loss of 0.3 kg in the glyburide group and a gain of 0.4 kg in the combined group. The package insert also described a double-blind controlled study in subjects with poorly controUed Type 2 diabetes, comparing metformin (2.5 g/day) to placebo. Weight loss in the placebo group was 1.1 kg, compared to 0.6 kg in the metformin group (Scheen, Letiexhe, & Lefebvre, 1995). Lee and Morley (1998), however, compared 48 w o m e n with Type 2 diabetes in a double-blind controlled trial, randomly assigning subjects to metformin (i.e., 850 m g twice daily) or placebo. Subjects on metformin lost 8.8 kg over 2 4 weeks, compared to only 1.0 kg in the placebo group (p < .001). Although metformin m a y not produce enough weight loss to receive an indication from the U.S. Food and Drug Administration for treating obesity, it certainly deserves consideration in obese individuals with Type 2 diabetes w h o have not achieved control of their disease with diet and exercise treatment. This medication has been used in chUdren (Lutjens & S m h , 1977).
Hydroxycitrate The -(-)hydroxycitrate isomer is an inhibitor of ATP-citrate lyase, the rate-limiting enzyme in lipogenesis. In experimental animals, Sullivan, Trscari, Hamilton, and Miller (1974) showed that this drug reduced food intake and body weight. Clinical data have been disap-
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pointing, however (Bray & Greenway, 1999). In a 3-month trial of an herbal product containing a source of hydroxycitrate, placebo-treated patients lost as m u c h weight as did those treated with the herbal product (Heymsfield et al., 1998). SimUarly, hydroxycitrate did not stimulate oxygen consumption in h u m a n subjects (Kriketos, T h o m p s o n , Greene, & Hill, 1999).
Drugs Approved for an Indication Other Than Obesity Dehydroepiandrosterone Dehydroepiandrosterone ( D H E A , or A^-androstene-3-|3-hydroxy-17-one) is produced by the adrenal gland. In h u m a n beings, this steroid and its sulfated derivative are the most abundant steroids produced by the adrenal glands. D H E A levels decline with age in both m e n and w o m e n (Svec & Porter, 1998). Mice, rats, cats, and dogs fed D H E A lose weight. A recent structure-function analysis by Lardy, Kneer, Wei, Partridge, and M a r w a h (1998) showed that the biological effect on body fat of DHEA-related steroids was greatest with 7o x o - D H E A derivatives. Several clinical studies of obesity have been carried out with D H E A (Bray & Greenway, 1999; Clore, 1995). In a study lasting 28 days with 10 normal-weight volunteers, D H E A at 1,600 mg/day, near the limit where hepatic toxicity is a risk, had no effect on body weight or on insulin sensitivity as assessed by the euglycemic-hyperinsulinemic clamp (Nestler, Barlascini, Clore, & Blackard, 1988). A similar study showed no effect of D H E A on energy expenditure, body composition, or protein turnover (Welle, Jozefowicz, & Statt, 1990). After 28 days of treatment with D H E A , obese male volunteers showed no improvement in body fat or insuhn sensitivity (Usiskin et al., 1990). In obese female volunteers there was likewise no change in body fat, but there was a decrease in insulin sensitivity (Mortola &c Yen, 1990). Based on these negative studies in both lean and obese h u m a n subjects, it would appear that D H E A is ineffective in h u m a n obesity. A steroid derivative of D H E A called etiocholanedione has, in one preliminary study, been suggested to reduce body weight (Zumoff, Strain, Heymsfield, & Lichtman, 1994). More data are awaited.
Testosterone and Dihydrotestosterone Testosterone is the principal product of the testes and is responsible for masculinization (Bray & Greenway, 1999). The inverse relationship benveen testosterone and visceral fat in m e n suggested the possibility that visceral fat might be reduced by treatment with testosterone. Marin and colleagues (1992, 1993) have evaluated this in two trials with older men w h o had low-normal circulating testosterone levels (<20 nmol/liter) and a body mass index (BMI) > 25 kg/m^. In the first trial, testosterone (80 m g twice daily) was given orally as the undecenoate (Marin et al., 1992). The 11 m e n w h o received testosterone had a significant decrease of visceral fat mass as measured by computed tomography, compared to the 12 m e n w h o received placebo for 8 months. There were no changes in body mass, subcutaneous fat mass, or lean body mass; insulin sensitivity was improved (Marin et al., 1992). In the second trial (Marin et al., 1993), 31 m e n were randomly allocated to three groups that received either placebo, testosterone, or dihydrotestosterone. The testosterone was given as a gel, with 5 g containing 125 m g of testosterone applied to the arms daily. The dihydrotestosterone was applied in a similar gel at the same dose. The placebo group received only the gel. After 9 months, the testosterone-treated group showed a significant decrease in waist circumference and visceral fat.
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Two addhional studies have examined the effects of anabolic steroids in men and w o m e n (Bray & Greenway, 1999; Lovejoy et al., 1995, 1996). Thefirstwas a 9-month trial on 30 healthy overweight m e n with m e a n B M I values of 33.8-34.5 kg/m^ and testosterone values between 2 and 5 ng/ml (Lovejoy et al., 1995). During thefirst3 months w h e n an oral anabolic steroid (oxandrolone) was given daily, there was a significantly greater decrease in subcutaneous fat and a greater fall in visceral fat than in the groups treated with placebo or testosterone enanthate injected every 2 weeks. Because of the drop in H D L cholesterol, which is a k n o w n side effect of oral anabolic steroids (Lovejoy et al., 1996), the anabolic steroid w a s changed to an injectable drug, nandrolone decanoate. The effects were similar to those of testosterone enanthate. The data with testosterone given as a biweekly injection did not replicate the data of Marin and colleagues (1992, 1993), and the biweekly injections of nandrolone failed to maintain the difference seen with daily treatment with oxandrolone. This suggests that to obtain the visceral effects with steroids, frequent if not daily administration m a y be needed.
D R U G S T H A T INCREASE E N E R G Y EXPENDITURE Thyroid Hormones The use of thyroid hormones to treat obesity is the oldest use of a thermogenic strategy (Bray, 1975; Bray & Greenway, 1999; Danforth, 1983). The concept is based on the early reports of "low metabohc rate" in obese subjects, which probably resulted from inappropriate correction for the higher body weight. It is clear that thyroid hormones will increase weight loss (Bray, Melvin, & Chopra, 1973), but this occurs with mobilization of both fat and lean tissues. Even small doses of triiodothyronine will enhance breakdown of bone and muscle (Lovejoy et al., 1997). This, accompanied with the increase in heart rate (Bray & Greenway, 1999; Bray et al., 1973), makes it inappropriate to use thyroid hormones alone to treat obesity.
Ephedrine and Caffeine Ephedrine is an isomer of PPA. The hydroxyl group on the a carbon prolongs its duration of action, and the methyl group on the (3 carbon, as well as the amino group, increases its peripheral actions and decreases its central actions on adrenergic receptors (Bray & Greenway, 1999). The mechanism by which ephedrine affects weight is due at least in part to its effect upon thermogenesis. Astrup, Lundsgaard, Madsen, and Christensen (1985) examined excess oxygen consumption in individuals w h o took an oral dose of ephedrine compared to placebo. Three hours after administration of a 1-mg/kg dose, oxygen consumption in the ephedrine and placebo groups was 1.3 ± 1.1 and 1.2 ± 1.1 liters, respectively. After chronic treatment with ephedrine (60 mg/day), oxygen consumption increased to 7.0 ± 2.3 and 6.9 ± 1.8 liters after 4 and 12 weeks of continuous treatment (p < .01), respectively. Obese subjects have been shown to have a reduced thermogenic response to cold exposure and to ephedrine. The thermogenic response to cold exposure was not affected by 5 weeks of exercise training, but the thermogenic response to ephedrine was slightly improved (1.1 ± .23 vs. 1.4 ± .17 kj/kg lean body mass/180 minutes; p < .06) (Nielsen, Astrup, Samuelson, W e n g holt, & Christensen, 1993). Thermogenesis m a y be only one w a y that ephedrine exerts its effect. Jonderko and Kucio (1991) have demonstrated that ephedrine (50 m g orally) significantiy delays gastric emptying compared to a placebo. The amount of food remaining in the
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stomach after 9 0 minutes w a s 7 0 . 3 % ± 5 . 1 % after placebo and 8 0 . 9 % ± 3 % in the ephedrine group (p < .02), which m a y represent a mechanism for decreased hunger. In a 6-month trial, Astrup, Breum, Toubro, Hein, and Q u a a d e (1992) compared placebo, caffeine (600 mg/day), ephedrine (60 mg/day), and the combination of caffeine with ephedrine in 180 obese subjects (Figure 15.5). Withdrawals were equal in aU groups, and 141 subjects completed the trial. Weight loss w a s significantly greater in the group receiving both caffeine and ephedrine (16.6 ± 8.6 kg vs. 13.2 ± 6.6 kg; p < .0015). Weight loss in the caffeine-only group and the ephedrine-only group w a s not different from that in the placebo group. Side effects of tremor, insomnia, and dizziness were transient, and by 8 weeks were n o different from those in the placebo group. Blood pressure fell equally in all four groups. After 6 months, the medication w a s stopped for 2 weeks to assess withdrawal symptoms. O n e hundred twenty-seven subjects then entered a 6-month open-label study of caffeine (600 mg/day) with ephedrine (60 mg/day) (Toubro, Astrup, Breum, & Quaade, 1993). T h e 99 subjects w h o completed the study lost an additional 1.1 kg (p < .02), and no clinically significant withdrawal symptoms were observed (Figure 15.5). Caffeine and ephedrine, in the one other long-term controlled trial that combined two medications for weight loss (Weintraub, 1992), gave 1 6 % loss of initial body weight over 6 months, which w a s maintained for the remainder of the year of treatment.
Pa-Adrenergic Receptor Agonists The sympathetic nervous system has a tonic role in maintaining energy expenditure and blood pressure. Blockade of the thermogenic part of this system will reduce the thermic response to a meal. N E , the neurotransmitter of the sympathetic nervous system, m a y also decrease food intake by acting on (32- or P3-adrenergic receptors. Several synthetic ^3 agonists
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have been developed against the animal P3 receptor, but the chnical responses have been disappointing (Arch & Wilson, 1996; Bray & Greenway, 1999; Connacher, Bennett, & Jung, 1992). After cloning of the h u m a n (33 receptor, several n e w compounds are being synthesized. Results of clinical trials are awaited.
PATIENT SELECTION F O R D R U G T R E A T M E N T The BMI can serve as a guide to the risk-benefit evaluation of an overweight patient (Bray, 1998b). Those patients w h o have a B M I above 30 kg/m^ are potential candidates for drug therapy. The presence of comorbidities such as dyslipidemia, hypertension, diabetes or impaired glucose tolerance, symptomatic osteoarthritis, or sleep apnea increases the rationale for treatment by shifting the B M I to 27-30 kg/m^ from a risk-adjusted B M I above 30 kg/m^ The currently available noradrenergic sympathomimetic drugs can reduce body weight, but only sibutramine is approved for long-term use. However, this drug should not be used in patients with stroke, congestive failure, or myocardial infarction. Orlistat is also approved for long-term use and for weight maintenance. Weight loss of 1 0 % - 1 5 % can improve health risks. However, faUure to lose weight or failure to improve comorbid conditions during treatment with a drug indicates either noncompliance with the drug or lack of response to the drug. Either situation requires reevaluation of therapy and addition of other medications or other modalities of treatment. As a guideline, patients being treated with drugs should lose more than 2 kg (4 pounds) in the first month, and should achieve and maintain more than a 5 % weight loss by 6 months. As long as weight loss is more than 5 % and/or the patient's comorbidities have improved, the drug m a y be continued. The data with phentermine (Figure 15.2) suggests that intermittent use m a y be beneficial. At least two groups of patients merit long-term drug therapy. The first group consists of patients w h o are considered for surgical treatment of their obesity. Individuals with a B M I above 35 kg/m^ should first be treated with antiobesity drugs. If they respond with more than a 1 5 % weight loss, drugs should be continued as long as they respond and their comorbidities improve. The second group of patients w h o deserve vigorous treatment consists of individuals with sleep apnea. A modest weight loss is often sufficient to alleviate their problem.
REFERENCES Apfelbaum, M., Vague, P., Ziegler, O., Hanotin, C, Thomas, F., & Leutenegger, E. (1999). Longterm maintenance of weight loss aher a V L C D : Sibutramine vs. placebo. American Journal of Medicine, 106, 179-194. Arch, J. R., Si WUson, S. (1996). Prospects for beta 3-adrenoceptor agonists in the treatment of obesity and diabetes [Review]. International Journal of Obesity, 20, 191-199. Astrup, A., Breum, L., Toubro, S., Hein, P., & Quaade, F. (1992). The effect and satiety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet: A double blind trial. International Journal of Obesity, 16,169-277. Astrup, A., Lundsgaard, C , Madsen, J., & Christensen, N. J. (1985). Enhanced thermogenic responsiveness during chronic ephedrine treatment in man. American Journal of Clinical Nutrition, 42, 83-94. Baez, M., Kursar, J. D., Helton, L. A., Wainscott, D. B., & Nelson, D. L. (1995). Molecular biology of serotonin receptors [Review]. Obesity Research, 3(Suppl. 4), 441-447.
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Bray, G. A. (1975). Thyroid hormones in the treatment of obesity. In Obesity in perspective: A conference sponsored by the John E. Fogarty International Center for Advanced Study in the Health Sciences. National Institutes of Health, Bethesda, Maryland, October 1-3, 1973 ( D H E W Publication N o . N I H 75-708, pp. 449-456), Washington, D C : U.S. Government Printing Office. Bray, G. A. (1993). Use and abuse of appetite suppressant drugs in the treatment of obesity. Annals of Internal Medicine, 119, 707-713. Bray, G. A. (1998a). Drug treatment of obesity: Don't throw out the baby with the bath water. American Journal of Clinical Nutrition, 67, 1-2. Bray, G. A. (1998b). Contemporary diagnosis and management of obesity. Newton, PA: Handbooks in Health Care. Bray, G. A., Atkinson, R. L., & Inoue, S. (1995). Pharmacologic treatment of obesity. Obesity Research, 3, 415S-632S. Bray, G. A., Blackburn, G. L., Ferguson, J. M., Greenway, F. L., Jain, A. K., Mendel, C. M., Mendels, J., Ryan, D., Schwartz, S. L., Scheinbaum, M . L., Sc Seaton, T. B. (1999). Sibutramine produces dose-related weight loss. Obesity Research, 7, 189-198. Bray, G. A., Sc Greenway, F. L. (1999). Current and potential drugs for treatment of obesity. Endocrine Reviews, 20(6), 805-875. Bray, G. A., & Inoue, S. (1992). Pharmacological treatment of obesity. American Journal of Clinical Nutrition, 55, 151S-319S. Bray, G. A., Melvin, K. E., & Chopra, I. J. (1973). Effect of triiodothyronine on some metabolic responses of obese patients. American Journal of Clinical Nutrition, 26, 715-711. Bray, G. A., Ryan, D. H., Gordon, D., Heidingsfelder, H., Cerise, F., Sc Wilson, K. (1996). A doubleblind randomized placebo-controlled trial of sibutramine. Obesity Research, 4, 163-170. Bray, G.A., Sc Tartaglia, L. A. (2000). Medicinal strategies in the treatment of obesity. Nature, 404, 671-677. Campbell, I. W., Menzies, D. G., Chalmers, J., McBain, A. M., & Brown, I. R. (1994). One year comparative trial of metformin and glipizide in Type 2 diabetes mellitus. Diabetes and Metabolism, 20, 394-400. Canovatchel, W . (1997). Long-term tolerabUity profile of orhstat, an intestinal lipase inhibitor [Abstract]. Diabetologia, 40, A196. Clore, J. N . (1995). Dehydroepiandrosterone and body fat. Obesity Research, 3, 613S-616S. Connacher, A. A., Bennett, W . M., Sc Jung, R. T. (1992). Clinical studies with the beta-adrenoceptor agonist B R L 26830A [Review]. American Journal of Clinical Nutrition, 55(Suppl. 1), 258-261. Connolly, H. M., Crary, J. L., M c G o o n , M . D., Hensrud, D. D., Edwards, B. S., Edwards, W . D., & Schaff, H. V. (1997). Valvular heart disease associated with fenfluramine-phentermine. N e w England Journal of Medicine, 337, 581-588. Danforth, E. (1983). The role of thyroid hormones and insuhn in the regulation of energy metabolism. American Journal of Clinical Nutrition, 38, 1006-1017. Davidson, M . H., Hauptman, J., DiGirolamo, M., Foreyt, J. P., Halsted, C. H., Heber, D., Heimburger, D. C , Lucas, C. P., Robbins, D. C , Chung, J., & Heymsfield, S. B. (1999). Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: A randomized controlled trial. Journal of the American Medical Association, 281, 235-242. Enzi, G., Baritussio, A., Marchiori, E., Sc Crepaldi, G. (1976). Short-term and long-term clinical evaluation of a non-amphetaminic anorexiant (mazindol) in the treatment of obesity. Journal of Internal Medicine Research, 4, 305-318. Farooqi, I. S., Jebb, S. A., Langmack, G., Lawrence, E., Cheetham, C. H., Prentice, A. M., Hughes, I. A., McCamish, M . A., & O'Rahilly, S. (1999). Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N e w England Journal of Medicine, 341, 879-884. Flint, A., Raben, A., Astrup, A., & Hoist, J. J. (1998). Glucagon-like peptide 1 promotes satiety and suppresses enet^ intake in hnmans. Journal of Clinical Investigation, 101, 515-520. Fontbonne, A., Charles, M . A., Juhan-Vague, I., Bard, J. M., Andre, P., Isnard, F., Cohen, J. M., Grandmottet, P., Vague, P., Safar, M . E., & Eschwege, E. (1996). The effect of metformin on the metabolic abnormalities associated with upper-body fat disttibution: B I G P R O Study Group. Diabetes Care, 19, 920-926.
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Greenway, F. (1992). Clinical studies with phenylpropanolamine: A meta-analysis. American Journal of Clinical Nutrition, 55, 203S-205S. Guerciolini, R. (1997). M o d e of acfion of orhstat. International Journal of Obesity, 21, S12-S23. GutzwUler, J. P., Drewe, J., Goke, B., Schmidt, H., Rohrer, B., Lareida, J., & Beglinger, C. (1999). Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus Type 2. American Journal of Physiology, 276, R1541-R1544. Guzelhan, C , Odink, J., Niestijl Jansen-Zuidema, J. J., Sc Hartmann, D. (1994). Influence of dietary composition on the inhibition of fat absorption by orlistat. Journal of Internal Medicine Research, 22, 255-165. Halford, J. C. G., Heal, D. J., & Blundell, J. E. (1994). Investigation of a new potential anti-obesity drug, sibutramine, using the behavioral satiety sequence. Appetite, 23, 306-307. Hanotin, C , Thomas, F., Jones, S. P., Leutenegger, E., & Drouin, P. (1998). Efficacy and tolerability of sibutramine in obese patients: A dose-ranging study. International Journal of Obesity, 22, 32-58. Hansen, D. L., Toubro, S., Stock, M . J., Macdonald, I. A., Si Astrup, A. (1998). Thermogenic effects of sibutramine in humans. American Journal of Clinical Nutrition, 68, 1180-1186. Hauptman, J., Guerciohni, R., & Nicholas, G. (1999). Orhstat: A novel treatment for obesity. In G. A. Bray & D. H . Ryan (Eds.), Pennington Center nutrition series: Vol. 9. Nutrition, genetics, and obesity (pp. 530-547). Baton Rouge: Louisiana State University Press. Hauptman, J. B., Jeunet, F. S., & Hartmann D. (1992). Initial studies in humans with the novel gastrointestinal lipase inhibitor R o 18-0647 (tetrahydrolipstatin). American Journal of Clinical Nutrition, 55, 309S-313S. Heal, D. J., Frankland, A. T., Gosden, J., Hutchins, L. J., Prow, M . R., Luscombe, G. P., & Buckett, W . R. (1992). A comparison of the effects of sibutramine hydrochloride, bupropion and methamphetamine on dopaminergic function: Evidence that dopamine is not a pharmacological target for sibutramine. Psychopharmacology, 107, 303-309. Heymsfield, S. B., Allison, D. B., VasseUi, J. R., Pietrobelli, A., Greenfield, D., & Nunez, C. (1998). Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: A randomized controlled trial. Journal of the American Medical Association, 280, 1596-1600. Heymsfield, S. B., Greenberg, A. S., Fujioka, K., Dixon, R. M., Kushner, R., Hunt, T., Lubina, J. A., Patane, J., Self, B., Hunt, P., & McCamish, M . (1999). Recombinant leptin for weight loss in obese and lean adults: A randomized, controlled, dose-escalation trial. Journal of the American Medical Association, 282, 1568-1575. HiU, J. O., Hauptman, J., Anderson, J. W., Fujioka, K., O'Neil, P. M., Smith, D. K., Zavoral, J. H., & Aronne, L. J. (1999). Orlistat, a lipase inhibitor, for weight maintenance aher conventional dieting: A 1-y study. American Journal of Clinical Nutrition, 69, 1108-1116. Hollander, P., Elbein, S. C , Hirsch, I. B., KeUey, D., McGill, J., Taylor, T., Weiss, S. R., Crockett, S. E., Kaplan, R. A., Comstock, J., Lucas, C. P., Lodewick, P. A., Canovatchel, W., Chung, J., & Hauptman, J. (1998). Role of orlistat in the treatment of obese patients with Type 2 diabetes. Diabetes Care, 21, 1288-1294. Inoue, S. (1995). Clinical studies with mazindol. Obesity Research, 3, S549-S552. James, W . P., Astrup, A., Finer, N., Hilsted, J., Kopelman, P., Rossner, S., Saris, W . H., Si Van Gaal, L. F. (2000). Effect of sibutramine on weight maintenance aher weight loss: A randomised trial. Lancet, 356, 2119-2125. Jonderko, K., Si Kucio, C. (1991). Effect of antiobesity drugs promoting energy-expenditure, yohimbine and ephedrine, on gastric-emptying in obese patients. Alimentary Pharmacology and Therapeutics, 5, 4 1 3 ^ 1 8 . Jones, S. P., Smith, I. G., Kelly, F., Si Gray, J. A. (1995). Long-term weight loss with sibutramine [Abstract]. International Journal of Obesity, 19, 40. Kalra, S. P., Dube, M . G., Pu, S., X u , B., Horvath, T. L., &; Kalra, P. S. (1999). Interacting appetiteregulating pathways in the hypothalamic regulation of body weight [Review]. Endocrine Reviews, 20, 68-100. Kriketos, A. D., Thompson, H. R., Greene, H., & HiU, J. O. (1999). (-)-Hydroxycitric acid does not affect energy expenditure and substrate oxidation in adult males in a post-absorptive state. International Journal of Obesity, 23, 867-873.
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Lardy, H. E., Kneer, N., Wei, Y., Partridge, B., & Marwah, P. (1998). Ergosteroids: II. Biologicallyactive metabolites and synthetic derivatives of dehydroepiandrosterone. Steroids, 63, 158-165. Lean, M . E. J. (1997). Sibutramine: A review of clinical efficacy. International Journal of Obesity, 21, S30-S36. Lee, A., Si Morley, J. E. (1998). Metformin decreases food-consumption and induces weight-loss in subjects with obesity with Type-II non-insulin-dependent diabetes. Obesity Research, 6, 47-53. Lockene, A., Skottova, N., & Olivecrona, G. (1994). Interactions of lipoprotein lipase w h h the activesite inhibitor tetrahydrolipstatin (orlistat). European Journal of Biochemistry, 222, 395-403. Lovejoy, J. C , Bray, G. A., Bourgeois, M . O., MacchiaveUi, R., Rood, J. C , Greeson, C , Si Partington, C. (1996). Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal w o m e n : A clinical research center study. Journal of Clinical Endocrinology and Metabolism, 81, 2198-2203. Lovejoy, J. C , Bray, G. A., Greeson, C. S., Klemperer, M., Morris, J., Partington, C , & TuUey, R. (1995). Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases abdominal fat in obese, older men. International Journal of Obesity, 19, 614-624. Lovejoy, J. C , Smith, S. R., Bray, G. A., DeLany, J. P., Rood, J. C , Gouvier, D., Windhauser, M., Ryan, D. H., MacchiaveUi, R., Si TuUey, R. A. (1997). Paradigm of experimentally induced mild hyperthyroidism: Effects on nitrogen balance, body composition, and energy expenditure in healthy young men. Journal of Clinical Endocrinology and Metabolism, 82, 765-770. Lustig, R. H., Rose, S. R., Burghen, G. A., Velasquez-Mieyer, P., Broome, D. C , Smith, K., Li, H., Hudson, M . M., Heideman, R. L., & Kun, L. E. (1999). Hypothalamic obesity caused by cranial insult in children: Altered glucose and insulin dynamics and reversal by a somatostatin agonist. Journal of Pediatrics, 135, 161-168. Lutjens, A., Si Smit, J. L. (1977). Effect of biguanide treatment in obese children. Helvetica Paediatrica Acta, 31, 473-480. Mantazoros, C. S. (1999). The role of leptin in human obesity and disease: A review of current evidence. Annals of Internal Medicine, 130, 671-680. Marin, P., Holmang, S., Gustafsson, C , Jonsson, L., Kvist, H., Blander, A., Eldh, J., Sjostrom, L., Holm, G., & Bjorntorp, P. (1993). Androgen treatment of abdominally obese men. Obesity Research, 1, 245-251. Marin, P., Holmang, S., Jonsson, L., Sjostrom, L., Kvist, H., Holm, G., Lindstedt, G., Si Bjorntorp, P. (1992). The effects of testosterone treatment on body composition and metabolism in middleaged obese men. International Journal of Obesity, 16, 991-997. Melia, A. T., Zhi, J., Koss-Twardy, S. G., Min, B. H., Smith, B. L., Freundlich, N . L., Arora, S., Sc Passe, S. M . (1995). The influence of reduced dietary fat absorption induced by orlistat on the pharmacokinetics of digoxin in healthy volunteers. Journal of Clinical Pharmacology, 35, 840-843. Montague, C. T., Farooqi, S., Whitehead, J. P., Soos, M . A., Rau, H., Wareham, N . J., Sevrter, C. P., Digby, J. E., M o h a m m e d , S. N., Hurst, J. A., Cheetham, C. H., Earley, A. R., Barnett, A. H., Prins, J. B., & O'Rahilly, S. (1997). Congenital leptin deficiency is associated with severe earlyonset obesity in humans. Nature, 387, 903-908. Mortola, J. F., & Yen, S. S. C. (1990). The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. Journal of Clinical Endocrinology and Metabolism, 71, 696-704. Munro, J. F., MacCuish, A. C , Wilson, E. M., Si Duncan, L. J. P. (1968). Comparison of continuous and intermittent anorectic therapy in obesity. British Medical Journal, i, 352-356. Nestler, J. E., Batiascini, C. O., Clore, J. N., 6c Blackard, W . G. (1988). Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. Journal of Clinical Endocrinology and Metabolism, 66, 57-61. Nielsen, B., Astrup, A., Samuelsen, P., Wengholt, H., Sc Christensen, N . J. (1993). Effect of physical training on thermogenic responses to cold and ephedrine in obesity. Intemational Journal of Obesity, 17, 383-390. Reitsma, J. B., Castro Cabezas, M., de Bruin, T. W., Sc Erkekns, D. W . (1994). Relationship between improved postprandial lipemia and low-density lipoprotein metabolism during treatment with tetrahydrolipstatin, a pancreatic lipase inhibitor. Metabolism, 43, 293-298.
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RoUs, B. J., Shide, D. J., Thorwart, M. L., & Ulbrecht, J. S. (1998). Sibutramine reduces food intake in non-dieting w o m e n with obesity. Obesity Research, 6, 1-11. Ryan, D. H., Bray, G. A., Helmcke, F., Sander, G., Volaufova, J., Greenway, F., Subramaniam, P., Sc Glancy, D. L. (1999). Serial echocardiographic and cUnical evaluation of valvular regurgitation before, during, and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine. Obesity Research, 7, 313-322. Ryan, D. H., Kaiser, P., Si Bray, G. A. (1995). Sibutramine: A novel new agent for obesity treatment. Obesity Research, 3(Suppl. 4), 553-559. Scheen, A. J., Letiexhe, M . R., & Lefebvre, P. J. (1995). Short administration of metformin improves insulin sensitivity in android obese subjects with impaired glucose tolerance. Diabetic Medicine, 12, 985-989. Schteingart, D. E. (1992). Effectiveness of phenylpropanolamine in the management of moderate obesity. International Journal of Obesity, 16, 4 8 7 ^ 9 3 . Seagle, H. M., Bessesen, D. H., & HiU, J. O. (1998). Effects of sibutramine on resting metabolic rate and weight loss in overweight w o m e n . Obesity Research, 6, 115-121. Sjostrom, L., Rissanen, A., Andersen, T., Boldrin, M., Golay, A., Koppeschaar, H. P., Si Krempf, M . (1998). Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients: European Multicentre Orlistat Study Group. Lancet, 352, 167-172. Smith, G. P. (Ed.). (1998). Satiation: From gut to brain. N e w York: Oxford University Press. Stock, M . J. (1997). Sibutramine: A review of the pharmacology of a novel anti-obesity agent. International Journal of Obesity, 21, S25-S29. Sullivan, A. C , Triscari, J., Hamilton, J. G., Si MUler, O. N . (1974). Effect of (-)-hydroxycitrate upon the accumulation of lipid in the rat: II. Appetite. Lipids, 9, 129-134. Svec, F., Si Porter, J. R. (1998). The actions of exogenous dehydroepiandrosterone in experimental animals and humans. Proceedings of the Society of Experimental Biology and Medicine, 218, 174-191. Tonstad, S., Pometta, D., Erkelens, D. W., Ose, L., Moccetti, T., Schouten, J. A., Golay, A., Reitsma, J., Del Bufalo, A., & Pasotti E. (1994). The effects of gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. European Journal of Clinical Pharmacology, 46, 405-410. Toubro, S., Astrup, A., Breum, L., & Quaade, F. (1993). The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans. International Journal of Obesity, 17(Suppl. 3), 73-77. U.K. Prospective Diabetes Study Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes (UKPDS 33). Lancet, 352, 837-853. Usiskin, K. S., Butterworth, S., Clore, J. N., Arad, Y., Ginsberg, H. N., Blackard, W . G., & Nestier, J. E. (1990). Lack of effect of dehydroepiandrosterone in obese men. International Journal of Obesity, 14, 4 5 7 ^ 6 3 . Weber, C , T a m , Y. K., Schmidtke-Schrezenmeier, G., Jonkmann, J. H., & van Brummelen, P. (1996). Effect of the lipase inhibitor orlistat on the pharmacokinetics of four different antihypertensive drugs in the healthy volunteers. European Journal of Clinical Pharmacology, 51, 87-90. Weintraub, M . (1985). Phenylpropanolamine as an anorexiant agent in weight control: A review of published and unpublished studies. In J. P. Morgan, D. V. Kagan, & J. S. Brody (Eds.), Clinical pharmacology and therapeutics series: Vol. 5. Phenylpropanolamine: Risks, benefits and controversies (pp. 53-79). N e w York: Praeger. Weintraub, M . (1992). Long-term weight control: The National Heart, Lung, and Blood Institute funded multimodal intervention study. Clinical Pharmacology and Therapeutics, 51, 581-585. Weintraub, M., Rubio, A., Golik, A., Byrne, L., Si Scheinbaum, M . L. (1991). Sibutramine in weight control: A dose-ranging, efficacy study. Clinical Pharmacology and Therapeutics, 50, 330-337. Welle, S., Jozefowicz, R., & Statt, M . (1990). Failure of dehydroepiandrosterone to influence energy and protein metabolism in humans. Journal of Clinical Endocrinology and Metabolism, 71, 1259-1264. Zhi, J., Meha, A. T., Eggers, H., Joly, R., & Patel, I. H. (1995). Review of limited systemic absorption
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of orlistat, a lipase inhibitor, in healthy human volunteers. Journal of Clinical Pharmacology, 35, 1103-1108. Zhi, J., Melia, A. T., Funk, C , Viger-Chougnet, A., Hopfgartner, G., Lausecker, B., W a n g , K., Fulton, J. S., Gabriel, L., Si MuUigan, T. E. (1996). Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers. Journal of Clinical Pharmacology, 36, 1006-1011. Zhi, J., Melia, A. T., Guerciolini, R., Chung, J., Kinberg, J., Hauptman, J. B., & Patel, I. H. (1994). Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers. Clinical Pharmacology and Therapeutics, 56, 82-85. Zhi, J., Melia, A. T., Koss-Twardy, S. G., Min, B., Guerciolini, R., Freundlich, N . L., Milla, G., & Patel, I. H. (1995). The influence of orlistat on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers. Journal of Clinical Pharmacology, 35, 521-525. Zumoff, B., Strain, G. W., Heymsfield, S. B., Si Lichtman, S. (1994). A randomized double-blind crossover study of the antiobesity effects of etiocholanedione. Obesity Research, 2, 13-18.
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RIFAT LATIFI J O H N M . KELLUM ERIC J. De M A R I A H A R V E Y J. S U G E R A A A N
A n estimated 9 7 million adults in the United States are overweight or obese. Thirty-two percent of the population is overweight, defined as having a body mass index (BMI) of 25-29.9 kg/m^, while 2 2 . 5 % are obese, with a B M I a 3 0 kg/m^ (National Heart, Lung, and Blood Institute [NHLBI], 1998). "Extreme obesity" is classified as a B M I > 4 0 kg/m^ and is associated with an extremely high risk of disease, especially cardiovascular disease ( N H L B I , 1998). A s the B M I increases, so does the mortality rate from aU causes, which is 1 0 0 % or more above that of persons w h o have a B M I of 20-25 kg/m^ (National Institutes of Health [NIH], 1992). Extreme obesity (previously referred to as "morbid obesity") is associated with several predictable significant clinical syndromes: (1) cardiovascular-related problems, such as coronary artery disease, heart failure, and increased complications following coronary artery bypass; (2) respiratory insufficiency due to obesity hypoventilation syndrome and obstructive sleep apnea syndrome (multiple nocturnal awakenings, loud snoring, falling asleep while driving, and daytime somnolence); (3) metabolic complications, such as diabetes mellitus, hypertension, elevated triglycerides, cholesterol, and gallstones; (4) increased intraabdominal pressure, which is manifested as stress overflow urinary incontinence, gastroesophageal reflux, nephrotic syndrome, hernias, venous stasis, pre-eclampsia, or nephrotic syndrome; (5) hypercoagulapathy; (6) increased intracranial pressure, leading to pseudotumor cerebri; (7) sexual hormone dysfunction, such as amenorrhea, hypermenorrhea, and Stein-Leventhal syndrome; (8) increased incidence of breast, uterine, colon, prostate, and other cancers; and (9) debilitating joint disease ( N H L B I , 1998; N I H , 1992). Furthermore, there are significant difficulties in diagnosing obese patients with such surgical conditions as peritonitis, necrotizing panniculitis, necrotizing fasciitis, diverticulitis, necrotizing pancreatitis, and other intra-abdominal infections. In addition, psychosocial impairment and work-related difficulties are integral parts of the pathology of extreme obesity (Wadden, Sarwer, Arnold, Gruen, & O'NeU, 2000). 339
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Recent studies have demonstrated that obesity is associated with a low-grade systemic inflammatory state, as manifested in elevated proinflammatory cytokines—interleukin 6 and C-reactive protein, thought to contribute to cardiovascular morbidity (Wisser, Bouter, McQuillan, Wener, & Harris, 1999). Elevated C-reactive protein levels have been associated with increased risk of myocardial infarction, stroke, peripheral arterial disease, and coronary heart disease (Wisser et al., 1999). Furthermore, bariatric surgery has been reported to be associated with significant decrease of cytokines (interleukin 3 and tumor necrosis factor), and this decrease w a s suggested to be responsible for alteration of the i m m u n e function after surgically induced weight loss (Kyzer, Binyamini, Chaimoff, & Fishman, 1999). Although the causes of severe obesity are multifactorial, the published success rate for all medical approaches, including pharmacotherapy and behavior modification for extreme obesity, is discouraging. It has been estimated that over 9 5 % of extremely obese patients subjected to medical weight reduction programs regain all of their lost weight, as w e U as additional excess weight, within 2 years of the onset of therapy (Bjorntorp, 1992; National Task Force on the Prevention and Treatment of Obesity, 1993). The surgical treatment of patients with a B M I > 4 0 kg/m^, or a B M I > 35 kg/m^ with comorbid conditions, has emerged as the definitive therapy and has gained increased acceptance a m o n g surgeons, physicians, and the public ( N H L B I , 1998). Although surgery is frequently employed w h e n other methods have failed, it should not be used in isolation, since it only addresses the calorie intake/assimilation side of the consumption-utilization equation. The effects of surgical procedures can be greatly improved by lifestyle changes, such as increased exercise, which increases calorie expenditure. S o m e surgical approaches m a y lead to nutritionally unsound weight reduction. For example, protein calorie malnutrition has been reported for each of the malabsorptive operations. Although some of these problems are attributable to poor patient compliance or failure to keep nutritional follow-up appointments, some appear to be intrinsic to the procedures themselves.
H I S T O R I C A L PERSPECTIVE Early Procedures Bariatric surgery has evolved over the last five decades. Although Henriksson (1952) reported thefirstsurgical treatment for extreme obesity, it w a s the w o r k of Payne and DeWinde (1969) beginning in 1956 that prompted other investigators to develop intestinal bypass surgery for severe obesity. This approach, which originally involved bypassing the proximal jejunum from end to side into the distal ileum, created a long blind segment of small intestine. It was widely adopted by general surgeons interested in bariatric surgery, but this procedure w a s prone to bacterial overgrowth and metabolic complications. "JejunoUeal bypass" (JIB) was the first popular surgical procedure for extreme obesity. During this procedure, a short length of proximal jejunum (8-14 inches) w a s connected to the distal ileum (4-12 inches) as an end-to-end or end-to-side anastomosis. This operation produced weight loss by obligatory malabsorption, through bypass of a major portion of the absorptive surface of the small intestine. However, h w a s associated with a number of serious early and late complications. The most serious postoperative comphcation w a s liver failure from cirrhosis. Other serious late sequelae were arthritis, gallstones, hypocalcemia, kidney stones, osteoporosis, intractable malodorous diarrhea with associated potassium and magnesium abnormalities, metabolic acidosis, vitamin 6^2 deficiency, vhamin K deficiency, interstitial nephritis with renal faUure, pneumatosis intestinalis and bypass enteritis associated with occuh blood in the stools, and iron deficiency anemia. Because of these significant
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complications, some have suggested that all JIB procedures should be reversed, because chrhosis can develop insidiously in the absence of abnormal liver function tests. In a study of 43 patients followed prospectively for 12.6 years w h o had intact JIB, some adverse effects (such as hypokalemia, cholethiasis, and vitamin B12 or folate deficiency) decreased over time. However, the incidence of diarrhea remained at 6 4 % , hypomagnesemia increased over time to 6 7 % , nephrolithiasis occurred in 3 3 % , and progressive hepatk fibrosis occurred in 3 8 % of patients (Hocking, Davis, Franzini, & W o o d w a r d , 1998). Because of these and other significant complication rates, standard JIB should no longer be performed. Furthermore, randomized prospective studies have shown that the gastric bypass operation is associated with a comparable weight loss and a significantly lower complication rate than JIB (Boman & DomeUoff, 1998). Since complications from the JIB can develop at any time, it is strongly suggested that these patients be followed up carefully, in order for complications to be diagnosed and treated promptly (Farndsen, Pedersen, & Richelsen, 1998). If a patient's cirrhosis is Child's A, the patient should be converted from the JIB to a Roux-en-Y gastric bypass ( R Y G B P ) , because simple takedown of the JIB has been associated with regain of all lost weight. O n the other hand, a Child's B cirrhosis, especially with esophageal varicies, m a y carry an excessive risk with conversion to R Y G B P , and a simple takedown of the JIB should be performed.
Gastric Bypass Mason and Ito (1969) at the University of Iowa introduced the concept of "gastric bypass," in which the stomach is compartmentalized into a small proximal segment and a m u c h larger distal, bypassed segment with drainage of the proximal gastric pouch into the proximal jejunum. This operation arose from Mason's observation that patients subjected to high subtotal gastrectomy for ulcer disease often lost weight. This operation has been refined over the years to include a Roux-en-Y jejunal limb for drainage of the proximal gastric pouch. In addition, the proximal gastric pouch has been reduced from an original 200-ml capacity to the present 15 to 20-ml pouch. It has been observed that certain nutrients that depend on gastric secretions for their normal absorption, such as iron, calcium, and vitamin B12, m a y become deficient in gastric bypass patients. In addition, marginal ulceration on the jejunal side of the gastrojejunostomy has been reported after this operation. Despite these shortcomings, R Y G B P is generally accepted as the benchmark operation by most bariatric surgeons.
Vertical Banded Gastroplasty Mason (1982) later introduced "vertical banded gastroplasty" (VBG), in which the stomach is compartmentalized with the use of a vertical staple line parallel to the lesser curvature of the stomach (see Figure 16.1). T h e outiet for drainage of the proximal gastric pouch into the distal gastric pouch is reinforced with a polypropylene mesh collar. V B G is superior to other pure gastric-restrictive operations in that it prevents stomal widening. Scopinaro and his colleagues in Genoa reintroduced malabsorptive methods in a blended operation that he called "pancreatobiliary diversion" (Scopinaro, Gianetti, Civalleri, Bonaluni, & Bachi, 1980; Scopinaro et al., 1981). In this operation, the distal stomach is resected and drained into a Roux-en-Y limb in which the small intestine is divided 250 c m proximal to the ileocecal valve and the distal end reanastomosed 50 c m from the ileocecal valve, with the proximal end used for the gastrojejunostomy.
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F I G U R E 16.1. Vertical banded gastroplasty. From Sugerman, Starkey, Si Birkenhauer (1987). Copyright 1987 by Lippincott WiUiams & Wilkins. Reprinted by permission.
C U R R E N T BARIATRIC O P E R A T I O N S Over the last decade, the safety and effectiveness of many surgical weight loss procedures have evolved. Currently, most bariatric surgical centers in North America and Europe perform V B G , adjusted gastric banding, or R Y G B P .
Gastroplasty In gastroplasty, the upper stomach is stapled near the gastroesophageal junction; this creates a small upper gastric pouch, which communicates with the rest of the stomach and gastrointestinal (GI) tract through a small outlet. The concept and the technique of gastroplasty were originally suggested as a safer and relatively easier method for restricting food intake. Gastroplasties are performed with either horizontal or vertical placement of the staples. Horizontal gastroplasty, which usually requires ligation and division of the short gastric vessels between the stomach and spleen, carries the risk of devascularization of the gastric pouch or splenic injury. Moreover, it has been associated with very high failure rates ( 4 2 % - 7 0 % ) . V B G , on the other hand, is a procedure in which a stapled opening is m a d e in the stomach with an end-to-end anastomosing (EEA) stapling device 5 c m from the cardioesophageal junction (see Figure 16.1). The pouch is constructed with a 9 0 - m m stapling device m a d e between this opening and the angle of His, and a 1.5-cm x 5-cm strip of polypropylene mesh is wrapped around the stoma on the lesser curvature and sutured to it-
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self but not to the stomach. VBG can be associated with severe gastroesophageal reflux. V B G is more effective than horizontal gastroplasty, but significantly less effective then R Y G B P , as demonstrated in randomized prospective trials in which several centers have reported inferior weight reduction with this operation as compared with standard R Y G B P (Bo & Modalsi, 1983; H a U et al., 1990; M a c L e a n , Rhode, Sampahs, & Forse, 1993; Sugerman, Starkey, &; Birkenhauer, 1987).
Gastric Banding Bo and Modalsli (1983) introduced gastric banding as a treatment for morbid obesity. In this technique, a Dacron tube or silicone band is used to compartmentalize the stomach into smaU proximal and large distal segments. This approach has the advantage of producing a pure restrictive operation using a very simple, reversible technique, in which stapling, with its inherent risk of staple line disruption, is avoided. M o r e recent developments include the introduction of an adjustable silicone gastric banding device, originally described by Kuzm a k (1992), which can be placed laparoscopically (see Figure 16.2). This band has a subcutaneous or subfascial reservoir. If weight loss is meager, or if vomiting is excessive, the outlet diameter of the upper gastric segment can be adjusted.
Gastric Bypass In recent years R Y G B P has become favored by most American bariatric surgeons as the procedure of choice in extremely obese patients, mainly because of superior long-term weight loss effects w h e n compared with V B G (see Figure 16.3). In randomized prospective trials, as well as retrospective studies, R Y G B P has been found to induce significantly greater weight loss than V B G . This is particularly true for patients w h o overconsume sweets. Such
F I G U R E 16.2. Ulustration of adjustable gastrk banding.
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F I G U R E 16.3. Illustration of Roux-en-Y gastric bypasses (RYGBP) for obesity. From Sugerman, Starkey, & Birkenhauer (1987). Copyright 1987 by Lippincott WiUiams & Wilkins. Reprinted by per-
patients are thought to lose weight more satisfactorily with R Y G B P than with V B G because the former procedure causes a dumping syndrome following the ingestion of foods rich in sugar. R Y G B P is associated with significantly higher levels of enteroglucagon than V B G . Furthermore, m a n y patients w h o have undergone V B G often fail to lose enough weight to correct their obesity-related comorbidity. Because of the high incidence of staple line disruption and ulcer formation, some surgeons recommend transecting the stomach for patients receiving gastric bypass (Kirkpatrick &c Zapas, 1998), especially those weighing over 4 0 0 pounds. Others have performed resectional gastric bypass as a n e w alternative weight control operation with extremely obese patients (Curry, Carter, Porter, & Watts, 1998). This operation, however, is suggested as an alternative for salvage of a failed or problematic prior bariatric procedure. However, with three to four superimposed applications of a 9 0 - m m stapler, the incidence of staple line disruption in our patients has been less than 2 % . Currently our group performs gastric bypass by constructing a small gastric pouch (15-30 ml) with a 45-cm Roux-en-Y limb and stoma restricted to 1 cm. (Appendix 16.1 provides a detaUed description of the operation.) Superobese patients ( B M I of 50 kg/m^ or greater) achieve a significantly better weight loss with a 150-cm Roux-en-Y limb (long-limb
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gastric bypass) (Brolin, Kenler, German, &c Cody, 1992). The small gastric pouch has a limhed volume of acid secretion and is associated with a low incidence of marginal ulcer. The loss of excess weight in patients undergoing gastric bypass averages 6 6 % at 2 years, 5 0 % at 10 years, and 4 7 % at 14 years after the surgery—far better than any results reported for dietary management (Pories et al., 1995).
L A P A R O S C O P I C BARIATRIC S U R G E R Y Laparoscopic bariatric surgery is still in its early phases of development. Although longterm results of this approach are not k n o w n , advantages should include a decreased length of hospital stay, less pain, and a lower risk of incisional hernia, which currently exceeds 2 0 % foUowing open obesity surgery. In addition, as with other laparoscopic surgeries, there should be fewer and less severe adhesions, with the potential for fewer subsequent smallbowel obstructions. The bariatric procedures currently performed laparoscopically include V B G , gastric banding (with adjustable bands), and R Y G B P . The success of laparoscopic bariatric surgery should be compared to that of standard open bariatric surgery. W e hope that this minimally invasive approach, in addition to decreasing the recovery time, will reduce perioperative complications of w o u n d infections and hernias.
Adjustable Gastric Banding The adjustable silicone gastric band has been developed to be placed laparoscopically. The device contains a balloon that is adjusted by injecting saline into a subcutaneously implanted port (see Figure 16.2). Although this procedure has become very popular in Europe and other parts of the world, there are no long-term studies validating its safety and efficacy. The results of a trial approved by the Food and Drug Administration in the United States are not yet available. Problems with band slippage leading to gastric obstruction and the need for reoperation, esophageal dilatation, band erosion into the lumen of the stomach, port infections, and inadequate weight loss have been reported. The presence of hiatal hernia and esophageal dysmotility was identified as independent risk factors for lap band slippage (Greenstein, Nissan, & Jaffin, 1999). Other complications of gastric banding include food intolerance, reflux esophagitis, pouch dilatation, and stoma occlusion. In a prospective randomized trial of open versus laparoscopic adjustable silicone gastric banding (LASGB), there were no differences in weight loss or postoperative complications for thefirstyear of follow-up ( D e W h , Mathus-Vliegen, Hey, Rademaker, & G o u m a , 1999). However, L A S G B was associated with a shorter initial hospital stay (5.9 days vs. 7.2 days; p < .05) and fewer admissions during 1-year foUow-up. O n the other hand, the operative time was significantly longer for the laparoscopic procedure. The total number of readmissions (6 vs. 15) and overall hospital stay for the first year (7.8 vs. 11.8 days) were lower for L A S G B [p < .05). The analysis of a multicenter study (Toppino, Morino, Bonnet, Nigra, S>c Siliquini, 1999) of 361 patients w h o underwent L A S G B and 120 patients w h o underwent laparoscopic V B G demonstrated that operative time and hospital stay were shorter in L A S G B . In addhion, L A S G B w a s associated with fewer complications. The weight loss, however, was significantly less in the L A S G B group. As in the DeWit and colleagues (1999) study, the follow-up in this study was too short. A number of patients with L A S G B have been converted to a gastric bypass. In some patients, the removal of gastric band and the conversion to R Y G B P can be performed laparo-
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scopically; however, these operations are technically challenging due to adhesions from the previous operation.
Gastric Bypass The initial experience with 75 patients w h o underwent laparoscopic R Y G B P (LRYGBP), using a 2 1 - m m E E A , was reported to be comparable to that w h h open R Y G B P . Furthermore, follow-up from 3 to 60 months on 500 patients w h o underwent L R Y G B P has been reported, with major complications in 1 1 % of patients, anastomotic leak in 5 % , and no mortahty (Witgrove & Clark, 1999). As experience is gained with L R Y G B P , complications related to the complex technical nature of the procedure will probably decrease. A s of this writing, most surgeons perform L R Y G B P in patients with B M I < 50 kg/m^, although a few groups have reported successful L R Y G B P in patients with a B M I up to 70 kg/m^ For the most part, the results are comparable to the open technique. However, the laparoscopic operation still takes significantly longer then the open technique, and mastering this procedure is difficult and the learning curve very steep.
PARTIAL B I U O P A N C R E A T I C D I V E R S I O N
A N D D U O D E N A L SWITCH OPERATIONS The partial biliopancreatic diversion has been developed as both a gastric-restrictive and a malabsorptive procedure that does not have a "blind" intestinal limb where bacterial overgrowth can occur. This operation involves a subtotal gastrectomy, leaving a 400-cc gastric pouch for the average obese patient and a 200-cc gastric pouch for the superobese patient. The distal small bowel is transected 250 c m proximal to the ileocecal valve, and the proximal, bypassed bowel is anastomosed to the ileum 50 c m proximal to the ileocecal valve. This leaves a 200-cm "alimentary tract"; a 300- to 400-cm "bihary tract" of bypassed intestine; and a 50-cm " c o m m o n absorptive alimentary tract," where the ingested food mixes with bile and pancreatic juices for digestion and absorption (see Figure 16.4). This operation has demonstrated excellent weight loss and does not appear to be associated with the high incidence of bacterial overgrowth and bacterial translocation problems of JIB, because bile and pancreatic juices wash out the bypassed small intestine. However, the biliopancreatic diversion m a y be associated with severe protein calorie malnutrition, necessitating hospitalization and total parenteral nutrition. It m a y also be associated with frequent, foulsmelling steatorrheic stools that float, leading to fat-soluble vitamin deficiencies and calcium loss secondary to chelation with fat, producing severe osteoporosis. Our group at the Medical College of Virginia (Liska, Sugerman, & Kellum, 1988) has described a modification of biliopancreatic diversion in which the stomach is merely stapled, as in gastric bypass, and the enteroenterostomy is placed 50-150 c m proximal to the ileocecal valve. This modification, which has been termed "distal gastric bypass," has been associated with better weight loss in superobese patients than standard gastric bypass has been. In a randomized prospective trial using a m u c h smaller proximal stomach pouch (50 cc), without gastric resection and a longer c o m m o n absorptive intestinal tract (150 cm), distal gastric bypass was associated with a m u c h greater weight loss than standard gastric bypass, but had a 2 5 % incidence of severe malnutrition (Liska et al., 1988). Four of 14 patients required conversion to a standard G B P due to protein calorie malnutrition. W e currently reserve distal gastric bypass for superobese patients w h o have had unsuccessful standard gastric bypass and have persistent obesity-related comorbidities (e.g., diabetes.
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150 cm
jejunum
ileum
FIGURE 16.4. Biliopancreatic diversion. From Scopinaro, Gianetti, Adami, et al. (1996). Copyright 1996 by Mosby. Reprinted by permission.
Pickwickian syndrome, etc.). These patients require fat-soluble vitamin supplementation and m a y develop severe malnutrition. A modified surgical procedure combining restriction and malabsorption, k n o w n as the "biliopancreatic diversion with a duodenal switch" operation, has been developed with the hope that there will be less protein and fat-soluble vitamin malabsorption (Lagace et al., 1995). In an effort to avoid bypass of the pylorus, Hess and Hess (1998) introduced the concept of wedge resection of the greater curvature of the stomach, combined with a "duodenal switch." This operation divides the d u o d e n u m in the distal bulb and the ileum 250 c m proximal to the ileocecal valve, with anastomosis of the proximal duodenal segment to the distal ileal segment. The distal end of the transected d u o d e n u m is oversewn as a duodenal stump. The proximal ileal segment, which carries the biliary and pancreatic secretions, is anastomosed from end to side for an enteroenterostomy 50-100 c m proximal to the ileocecal valve. The segment that carries the biliary and pancreatic secretions is anastomosed to the ileum 100 c m proximal to the ileocecal valve (see Figure 16.5). It is not yet clear whether this operation will prevent the protein malnutrition, calcium deficiency, and fatsoluble vitamin deficiencies associated with the partial biliopancreatic bypass procedure. This operation w a s performed in 440 patients as the initial bariatric procedure, and it was associated with weight loss of 7 0 % of excess weight 8 years after surgery (Hess & Hess, 1998). Seventeen of these patients underwent reoperations for excessive weight loss to
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\ PARIETAL GASTRECTOMY .' & DUODENAL SWITCH
WHOLE ALIMENTARY CHANNEL 250 CM
BILIOPANCREATIC LIMB
C O M M O N CHANNEL 100 c m FIGURE 16.5. The "duodenal switch" modification of biliopancreatic diversion. From Lagace et al. (1995). Copyright 1995 by FD-Communications, Inc. Reprinted by permission.
correct severe protein malnutrition. This operation w a s associated with improved quality of life. There were no marginal ulcers or cases of dumping syndrome.
C O M P L I C A T I O N S O F GASTRIC S U R G E R Y F O R E X T R E M E OBESITY Perioperative Complications Perioperative complications of patients undergoing surgery for extreme obesity, although not c o m m o n , m a y be significant. Complications must be recognized and addressed promptly in order to minimize possible mortality and morbidity. Intraoperative injuries to the spleen or other organs are rare. Following gastric bypass, the distal bypassed stomach occasionally will develop gaseous distention, secondary to afferent limb obstruction at the jejunojenunostomy anastomosis. This m a y lead to gastric perforation, staple line disruption, or disruption of the gastrojejunal anastomosis with a leak. This complication is usually heralded by frequent hiccups and can be diagnosed by noting a large gastric bubble on a plain abdominal roentgenogram. Impending gastric perforation requires urgent decompression. This can be performed via percutaneous technique or with operative decompression. In patients w h o undergo reoperation, such as conversion from JIB to gastric bypass, or in patients with extensive adhesions from previous abdominal surgery, a gastrostomy tube should be inserted prophylactically for decompression. T h e gastrostomy tube also can be used for feeding until a patient's oral intake permits weight stabilization, or for enteral nutritional support in patients w h o develop a leak from the proximal gastric pouch. Other acute surgical complications are w o u n d infections, w o u n d dehiscence, fistulas, and abdominal sepsis that m a y progress to multiple-system organ failure and death. The most feared early complication of gastric surgery for extreme obesity is a postoperative leak from the gastrojejunostomy, causing peritonitis. T h e inability to readily recognize an abdominal catastrophe is one of the most significant aspects of surgical care in extremely obese patients. T h e classic signs and symptoms of peritonitis in these patients are often absent. If a patient experiences worsening abdominal pain, back or left-shoulder pain, urinary frequency, or rectal tenesmus, a leak must be suspected. T h e presence of tachycardia.
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tachypnea, fever, leukocytosis, or metabolic acidosis also should raise strong suspicion of abdominal catastrophe. A leak can often be confirmed with an upper-GI roentgenographic series using water-soluble contrast. If a leak is observed, or even if the study is negative but the suspicion is high, the patient's a b d o m e n must be urgently explored. A n attempt to repair the leak should be m a d e , and a large s u m p drain placed nearby, because the repair frequently breaks d o w n . This leads to a controlledfistula,which requires therapy with total parenteral nutrition, a feeding gastrostomy, or jejunostomy. Other acute complications following gastric obesity surgery include deep vein thrombosis, pulmonary embolus, and superficial or deep w o u n d infections. Although these complications are not unique to gastric surgery for extreme obesity, they are more c o m m o n in this patient population. The incidence of lower-leg venous thrombosis and pulmonary embolism can be significantly reduced with the use of intermittent venous compression boots placed prior to the start of the operation and low-dose heparin or low-molecular-weight heparin given 30 minutes prior to surgery. Although there currently are no data to support low-molecular-weight heparin use in these patients, higher doses of this form of heparin may be needed, based on heparin antifactor X A levels (Martin & Finigan, 1999). For patients with obesity hypoventilation, pulmonary hypertension, or severe venous stasis disease at the time of obesity surgery, it has been recommended that a vena cava filter be placed prophylactically. Early ambulation is also very important in all patients w h o undergo gastric surgery for extreme obesity. A marginal ulcer develops in about 1 0 % of gastric bypass patients. This usually responds to acid suppression therapy (H2 receptor or proton p u m p blockers). In one report of 123 patients w h o underwent gastric bypass, staple line disruption occurred in 2 9 % of patients, while stomal ulcers occurred in 1 6 % (MacLean, Rhode, Nohr, Katz, & M c L e a n , 1997). O u r group has previously reported a m u c h lower rate of staple line disruption ( 2 % ) using multiple superimposed firings of a PI-90 staple (Kellum, D e Maria, & Sugerman, 1998). O n the other hand, gastrogastric fistula with stomal ulcer was significantly lower (3%) in 376 patients w h o had the stomach completely transected rather then stapled. Patients with stomal ulcer have higher acid output w h e n compared to patients without ulcer or with patients with gastrogastric fistula. Stomal stenosis can develop in patients following R Y G B P or V B G . Outpatient endoscopic balloon stomal dilation should be attempted and is usually successful in patients with stenosis following R Y G B P , but less effective in patients with stenosis following V B G .
Late Complications Rapid weight loss following either V B G or gastric bypass is associated with a high incidence ( 3 2 % - 3 5 % ) of gaUstone formation, with a 1 0 % need for subsequent cholecystectomy for acute bUiary colic or cholecystitis within 3-5 years of obesity surgery. Although some surgeons perform prophylactic cholecystectomy at the time of bariatric surgery, our group and others perform cholecystectomy only with sonographic evidence of gallstones. In a randomized prospective clinical trial, prophylactic ursodeoxycholic acid (300 m g orally twice daily) was shown to reduce the risk of gallstone formation from 3 2 % to 2 % w h e n given for 6 months after gastric bypass surgery. Moreover, there w a s a very low risk of subsequent gallstone formation for the 6 months following discontinuation of the medication (Sugerman et al., 1995b). Following either open R Y G B P or L R Y G B P , patients are at risk for developing an internal hernia with a closed-loop obstruction and strangulation. There are three potential locations for this hernia to occur. First, they m a y occur through the mesenteric defect at the jejunojejunostomy site; second, through the opening of transverse mesocolon though which
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the retrocolic Roux-en-Y limb is brought; and third, through the mesenteric defect located under the Roux-en-Y h m b before it passes through the mesocolon, k n o w n as a Petersen hernia. These hernias m a y manifest principally with periumbilical abdominal pain, and their diagnosis m a y be difficult. A computed tomography scan of the abdomen m a y be more helpful than upper-GI contrast studies in establishing the diagnosis. W h e n the diagnosis is uncertain and the radiological studies are not helpful, the safest coiurse of action is to reoperate in a patient with recurrent pain attacks, since massive intestinal infarction has been seen with these internal hernias. Another significant complication of bariatric surgery is incisional hernia, which in open surgery has an incidence of about 2 0 % . Furthermore, m a n y superobese patients require abdominoplasty foUowhig weight loss. Although abdominoplasty m a y be foUowed with complications in as m a n y as 5 5 % of patients (Vastine et al., 1999), previous bariatric surgery does not influence the rate of complications following this operation, and these patients should be offered body-contouring surgery w h e n indicated. The most important factor that will influence the complications following abdominoplasty is the degree of obesity at the time of the surgery, which has profound influence on w o u n d comphcations.
Nutritional Complications Following any gastric surgery for extreme obesity, significant nutritional complications such as protein calorie malnutrition m a y develop. Specifically, a very rare syndrome of polyneuropathy has been reported after these operations. This usually occurs in association with intractable vomiting and severe protein calorie malnutrition with subsequent acute thiamin deficiency. The risk of vitamin B12 deficiency mandates long-term follow-up with annual measurement of the vitamin B12 level. B12 deficiency is probably due to decreased acid digestion of vitamin B12 from food, with subsequent failure of coupling to intrinsic factor. Postoperatively patients should need to take 500 |JLg of oral vitamin B12 daily or 1 m g of vitamin B12 intramuscularly per month. Iron deficiency anemia most commonly occurs in menstruating w o m e n following gastric bypass. This can be refractory to supplemental ferrous sulfate because iron absorption takes place primarily in the duodenum and upper jejunum. Occasionally, iron dextran injections m a y be necessary. All menstruating w o m e n should take two iron sulfate tablets (325 mg/day) by mouth after gastric bypass as long as they continue to menstruate. Magnesium deficiency m a y also occur and require supplementation. Calcium supplementation is often necessary after any gastric bypass procedure. Patients with either a long-limb gastric or partial biliopancreatic bypass can develop calcium and fat-soluble vitamin deficiencies that need to be monitored and treated.
O U T C O M E S O F OBESITY S U R G E R Y Positive Outcomes Gastric procedures for extreme obesity can yield dramatic and long-term weight reduction, with an average loss of two-thirds of excess weight within 1-2 years. Weight becomes stable at this level and is well maintained at long-term follow-up. The patients must be followed carefully to ensure adequate protein, vitamin, and other micronutrient levels. Weight loss corrects non-insulin-dependent diabetes meUitus in almost all cases. N o other therapy has produced more durable and complete control of Type 2 diabetes (Pories
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et al., 1995). Hypertension is cured in two-thirds to three-fourths of patients, as well as the headaches that are associated with cerebrospinal fluid pressure elevation in almost all patients with pseudotumor cerebri (Kellum et al., 1998; Sugerman et al., 1999). T h e obstructive sleep apnea syndrome, which poses the greatest immediate risk to life of any extreme obesity complications, resolves with weight loss. T h e hypoventilation and hypercarbia seen in the obesity hypoventilation syndrome return toward normal with weight loss (Sugerman, Baron, Fairman, Evans, & Vetrovec, 1988). Elevated pulmonary artery and pulmonary capiUary wedge pressures also improve significantly following weight loss, with correction of abnormal arterial blood gases (Sugerman et al., 1988). Postsurgery weight loss is associated with significant improvement of left ventricular ejection fraction, and to some extent with improvements in cardiac chamber size and ventricular wall thickness (Alpert, Terry, & Kelly, 1985). Improvement in the lipid profile of extemely obese patients has been documented (Brolin al., 1990). A decrease in levels of cytokines following gastric surgery for obesity has also been reported (Kyzer, Binyamini, Chaimoff, &c Fishman, 1999). In addition, the loss of weight usually corrects female sexual hormone abnormalities; permits healing of chronic venous stasis ulcers associated with venous insufficiency; prevents reflux esophagitis; relieves stress overflow urinary incontinence; and improves low back pain, as well as joint-related pain. Furthermore, weight loss m a y permit successful total artificial joint replacement. Finally, patients' self-image and quality of life often improve dramatically following weight loss with bariatric surgery. T h e Swedish Obese Subjects study has documented significant decreases in depression and anxiety, as well as improvement in patients' social functioning (Sjostrom, Lissner, & Sjostrom, 1997). A s would be expected after weight loss, the Swedish patients reported far greater comfort in shopping for clothes, swimming in public, and even eating at restaurants.
Failed Gastric Surgery and Reoperation W e believe that a patient's inability to lose at least 4 0 % of excess weight should be considered a failure of obesity surgery. About 1 0 % - 1 5 % of patients regain lost weight or fail to achieve an acceptable weight loss. Although some patients can overcome a gastric bypass and regain weight by expanding either the stoma or pouch, this finding is not c o m m o n . T h e cause for this failure appears to be excessive, constant nibbling on foods with a high caloric density and/or failure to maintain regular exercise. Reoperation for failed gastric surgery for morbid obesity can be extremely challenging and can herald significantly higher risk for morbidity and possible mortality. Attempts to revise a failed gastroplasty are often unsuccessful because of recurrence of stomal dilatation and problems with gastric emptying. Reoperation in these patients is extremely difficult because of extensive adhesions to the liver and spleen. Results appear to be significantly better w h e n these patients are converted to R Y G B P . Because of the technical difficulties, these patients must understand that the risks of serious complications are far higher after a secondary than after a primary gastric bypass procedure. It is probably inappropriate and dangerous to convert a failed gastric bypass to V B G . Furthermore, revision of a dilated gastrojejunal stoma has not been effective (Schwartz, Strodel, Simpson, & Griffen, 1988). In most cases, a failed gastric bypass is a consequence of excessive fat ingestion. If a patient has significant obesity comorbidity that has failed to resolve or has returned with weight regain, conversion to a malabsorptive distal gastric bypass (modified partial biliopancreatic diversion) can be performed. This, however, can be associated with protein calorie malnutrition, steatorrhea, fat-soluble vitamin deficiencies, and osteoporosis.
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SUMMARY Bariatric surgery has emerged in the past decade as the treatment of choice for persons with extreme obesity w h o have not succeeded in losing weight via using m o r e conservative approaches. T h e R Y G B P , in particular, is associated with excellent long-term weight loss and with dramatic improvement in comorbid conditions. This success strongly argues that more individuals with a B M I > 4 0 kg/m^, or with a B M I > 3 5 kg/m^ and have significant health complications, should be considered for bariatric surgery.
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Sugerman, H. J., Brewer, W. H., Shiffman, M. L., Brohn, R. E., Fobi, M. A., Linner, J. H., MacDonald, K. G., MacGregor, A. M., Martin, L. F., Si Oram-Smith, J. C. (1995b). Prophylactk ursodeoxycholic acid prevents gallstone formation following gastric bypass induced rapid weight loss: A multicenter, placebo-controlled randomized, double-blind, prospective trial of prophylactic ursodiol for prevention of gallstone formation following gastric-bypass induced rapid weight loss. American Journal of Surgery, 169, 91-97. Sugerman, H. J., Felton, W . L., Ill, Sismasis, A., KuUum, J. M., D e Maria, E. J., Si Sugerman, E. L. (1999). Gastric surgery for pseudotumor cerebri associated with severe obesity. Annals of Surgery, 229, 634-642. Sugerman, H. J., Starkey, J. V., & Birkenhauer, R. A. (1987). A randomized prospective trial of gastric bypass versus vertical banded gastroplasty for morbid obesity and their effects on sweets versus non-sweet eaters. Annals of Surgery, 205, 613-624. Toppino, M., Morino, M., Bonnet, G., Nigra, I., & Sihquini, R. (1999). Laparoscopic surgery for morbid obesity: Preliminary results from SICE Registry (Italian Society of Endoscopic and Minimally Invasive Surgery). Obesity and Surgery, 9, 61-65. Vastine, V. L., Morgan, R. F., W U U a m s , G. S., Gampper, T. J., Drake, D. B., Knox, L. K., & Lin, K. Y. (1999). W o u n d complications of abdominoplasty in obese patients. Annals of Plastic Surgery, 42, 34-39. Wadden. T. A., Sarwer, D. B., Arnold, M . E., Gruen, D., & O'NeU, P. M . (2000). Psychosocial status of severely obese patients before and after bariatric surgery. Problems in General Surgery, 17, 13-11. Wisser, M., Bouter, M., McQuillan, G. M., Wener, M . H., Si Hartis, T. B. (1999). Elevated C-reactive protein levels in overweight and obese adults. Journal of the American Medical Association, 282, 2131-2135. Witgrove, A. C , Si Clark, G. W . (1999). Laparoscopic gastric bypass: Afive-yearprospective study of 500 followed from 3 to 60 months. Obesity and Surgery, 9, 124.
Surgical Treatment of Obesity
355
APPENDIX 16.1. OPERATIVE TECHNIQUE OF OPEN GASTRIC BYPASS The abdomen is entered through a midline incision carried superiorly alongside the xiphoid process and inferiorly to the umbilicus, or inferior enough to obtain adequate access (Sugerman, 1997). U p o n entering the peritoneal cavity, the surgeon performs a complete exploration to exclude unanticipated pathology before the gastric bypass is begun. If gallstones, sludge, or polyps are present on palpation or found on intraoperative ultrasound, then cholecystectomy is performed (Sugerman et al., 1995a). The distal esophagus is mobilized and encircled with a soft rubber drain. The gastrohepatic omentum is entered overlying the caudate lobe. A n aberrant left hepatic artery m a y be present and should be avoided (see Figure 16.6). The phrenoesophageal ligament overlying the anterior and lateral distal esophagus is sharply incised. This will facilitate blunt mobilization of the distal esophagus. Laterally, the dissection must be at the level of the esophagus. L o w lateral dissection m a y lead to injury of the short gastric vessels or spleen, or to creation of a large proximal pouch. A n opening is m a d e in the mesentery alongside the stomach between thefirstand a second branch of the left gastric artery, large enough to admit a right-angled clamp. Following blunt dissection of the avascular space on the posterior stomach wall, between the opening in the gastrohepatic o m e n t u m and the lateral angle of His, a rubber tube is placed that will serve as a guide for introduction of the stapling device (see Figure 16.6). Before staplers are applied, all intraluminal tubes (the nasogastric tube, the esophageal stethoscope) must be removed by the anesthesiologist. The ligament of Treitz is identified; 45 c m distally, the jejunum is divided with a G I A stapling device, and the Roux-en-Y limb is created. A side-to-side jejunojenunostomy is created at 45 c m for standard bypass or at 150 c m for superobese patients. With blunt dissection, an opening is created in the transverse colon mesentery, and the Roux-en-Y limb is brought through to the proximal stomach without tension. At this point a 5 5 - m m or 9 0 - m m stapling device is placed across the stomach, using the rubber tube as a guide. Once the surgeon is assured that the staple line is across the stomach, and that the stomach is not folded on itself, the stomach is stapled three times with superimposed staple applications.
F I G U R E 16.6. Illustration of atraumatic compartmentalization of the stomach for G B P . From Kellum, D e Maria, Si Sugerman (1998). Copyright 1998 by Mosby. Reprinted by permission.
356
T R E A T M E N T O F A D U L T OBESITY
A 1-cm gastrojejunal anastomosis is created between the proximal stomach and the Roux-en-Y limb. This anastomosis is hand-sewn, using a two-layer technique. Once the posterior layer of the anastomosis is sewn, a N o . 30 French dilator is placed by anesthesia and guided by the surgeon through the anastomosis. Following completion of the anastomosis, methylene blue dye is injected through a nasogastric tube to assess for possible leakage. All mesenteric defects are closed: at the jejunojenunostomy, at the mesocolon, and behind the Roux-en-Y limb to prevent a Petersen hernia (De Maria Si Sugerman, 1997). The abdominal fascia is closed with a running stitch, while the skin is approximated with skin staples.
1
7
Improving the Maintenance of Weight L o s t in
Behavioral
Treatment
of
Obesity
M I C H A E L G . PERRI J O Y C E A. C O R S I C A
Against the backdrop of a spreading obesity epidemic with serious public health consequences (AUison, Fontaine, M a n s o n , Stevens, & VanltaUie, 1999; M o k d a d et al., 1999) stand the stark findings of poor maintenance of treatment-induced weight loss (Perri, 1998). Long-term follow-up evaluations of obesity interventions indicate that weight losses accomplished through changes in diet and physical activity are rarely maintained, prompting some authors to suggest that behavioral interventions represent futile endeavors doomed to ultimate failure by the biology of obesity (WUson, 1994). Others view the same data and suggest that the problem of poor maintenance lies in a failure to develop a "continuous-care" approach to the treatment of obesity (Perri, Nezu, & Viegener, 1992). In this chapter, w e address the "maintenance problem" in the behavioral treatment of obesity. W e first review the long-term effects of behavioral treatments (i.e., lifestyle interventions derived from learning or social-cognitive theories, designed to promote weight loss through changes in eating and physical activity without the use of medications, very-lowcalorie diets, or surgery). After a brief look at contributors to posttreatment weight gain, w e examine the impact of extended treatments (i.e., those that continue beyond 6 months), as well as the effects of various other strategies designed to enhance the maintenance of treatment effects. W e conclude by discussing future clinical and research directions for the longterm behavioral management of obesity.
L O N G - T E R M EFFECTS O F B E H A V I O R A L T R E A T M E N T Long-term outcome can be gauged in several ways, including (1) by the net amount of weight change (in kilograms) from baseline; (2) by the percentage of posttreatment weight loss maintained; and (3) by the net percentage of change in body weight from baseline. Each of these indicators provides important information for judging long-term outcome. A n ad357
358
TREATMENT O F ADULT OBESITY
ditional key consideration is whether the degree of weight change is sufficient to improve health. Modest reductions in body weight (e.g., 5 % - 1 0 % of body weight), maintained for sufficient periods of time, can confer health improvements such as reductions in blood pressure, blood glucose, and hyperhpidemia (Pi-Sunyer, 1996). Thus the Institute of Medicine (lOM, 1995), in its report on criteria for assessing the outcome of weight management programs, has defined "success" as a weight loss of > 5 % of body weight maintained for 1 or more years. W e use the l O M definition, along with the other indicators noted above, in reviewing long-term outcome. Numerous studies have examined the short-term effects of behavioral treatment and outcome at 1-year foUow-up. Reviews (Brownell & W a d d e n , 1992; National Heart, Lung, and Blood Insthute [NHLBI], 1998; Perri, 1998; Perri & Fuller, 1995; W a d d e n , Sarwer, & Berkowitz, 1999) of randomized trials conducted during the 1990s show that behavioral treatments, typically delivered in 15-26 weekly group sessions, produced m e a n losses of approximately 0.4 kg/week of treatment and m e a n posttreatment losses of approximately 8.5 kg. (For more information on behavioral treatment, see Wing, Chapter 14, this volume.) Significant improvements in blood pressure, blood glucose, and psychological well-being have been associated with weight losses of this magnitude ( N H L B I , 1998; Pi-Sunyer, 1996). Nonetheless, the clinical utUity of an 8.5-kg loss is determined by h o w w e U the lost weight is maintained. The l O M (1995) succinctly summarized the longer-term findings, stating that "those w h o complete weight-loss programs lose approximately 10 percent of theh body weight, only to regain two thirds of it back within one year and almost aU of it back within 5 years" (p. 1). In Table 17.1, w e summarize the results of nine behavioral treatment studies with follow-ups of 2 or more years (Bjorvell & Rossner, 1985, 1992; Elmer et al., 1995; Graham, Taylor, Hovell, & Siegel, 1983; Hypertension Prevention Trial Research Group, 1990; Kramer, Jeffery, Forster, & SneU, 1989; Stalonas, Perri, & Kerzner, 1984; W a d d e n , Sternberg, Letizia, Stunkard, & Foster, 1989; W a d d e n , Stunkard, & Liebschutz, 1988; Whelton et al., 1998). Three of the studies included behavioral weight loss treatment as part of a hypertension reduction intervention (Elmer et al., 1995; Hypertension Prevention Trial Research Group, 1990; Whelton et al., 1998). The initial weight losses in these three trials were somewhat smaller than those usually observed in behavioral treatments with healthy adults, but their large sample sizes and long follow-up periods provide additional documentation about long-term outcome following behavioral treatment. Initial weight changes for the studies in Table 17.1 ranged from 4.5 to 14.3 kg (M across studies = 8.3 kg, unadjusted for study n). The magnitude of initial losses appears to reflect the length of treatment and the pretreatment weight of the samples. Studies with longer treatment periods and/or heavier subjects showed larger posttreatment losses. In each study, the mean reductions at 1-year follow-up met or exceeded the l O M criterion for successful maintenance (i.e., > 5 % reduction in body weight). Final foUow-up evaluations, conducted 2-12 years after initial treatment, showed a m e a n net loss of 3.0 kg (unadjusted for study n) across aU studies. However, only two of the nine studies met the l O M criterion for successful maintenance at final follow-up. The exceptions were one of the hypertension studies (Whelton et al., 1998), which had the shortest follow-up period (2 years), and the study by BjorveU and Rossner (1985, 1992), which showed a maintenance of a 10.6-kg loss 10-12 years after initial treatment. The obvious distinguishing feature of the Bjorvell and Rossner study was its inclusion of an intensive 4-year maintenance program that incorporated ongoing behavioral treatment, exercise, dietary counseling, and relapse prevention training, along with admission of relapsed patients to a day hosphal u n h for intensive treatment. If the Bjorvell and Rossner study is omitted from consideration because of its unusually intensive nature, the follow-up data in Table 17.1 suggest a reliable pattern of gradual
T A B L E 17.1. Studies of Behavioral Weight Loss Treatment with 2 Years or More of Follow-Up
Study
Tx. & length (wk)
n
Graham et al. (1983)
60
Stalonas et al. (1984)
36
Kramer et al. (1989)
152
BT
Net loss at 1 yr
lOMC met at 1 yr
Time Net loss tofinalf/u (kg) (yr) at final f/u
Pre-tx. wt. (kg)
Initial wt. loss (kg)
% initial loss l O M C " met maintained atfinalf/u?
NA
4.5
NA
NA
4.5
3.3
74%
NA
82
4.8
4.1
Yes
5.0
+0.7
-14%
No
98
11.5
6.6
Yes
4/5
2.7
23%
No
(NA)
BT (10)
BT (15)
Bjorvell 8c Rossner (1985)
74
Multicomponent^
125
11.1
23.0
Yes
4.0
15.0
100%
Yes
BjorveU & Rossner (1992)
49
Same
125
12.6
23.0
Yes
10-12
10.6
89%
Yes
16
BT
122
14.3
9.5
Yes
3.0
4.8
33%
No
106
13.0
4.7
Yes
5.0
+2.7
-21%
No
w Wadden et al. •O (1988) Wadden et al. (1989)
(16)
22
BT (26)
Hypertension Prevention Triab Research Group (1990)
254
BT-^ (14)
87
5.8
NA
Yes
3.0
1.6
29%
No
Elmer et al.*^ (1995)
902
BT'' (26)
85
5.0
4.8
Yes
3.5
2.6
52%
No
Whelton et al.-^ (1998)
147
BT
87
4.8
4.6
Yes
2.0
4.7
98%
Yes
(32)
Note. BT, behavior therapy; NA, not available; f/u, follow-up. " Institute of Medicine (1995) criterion for successful long-term loss—that is, s 5 % body weight lost and maintained for >1 year. * Data presented for multicomponent behavioral program, which included a 6-week inpatient stay, relapse prevention, exercise, nutritional counseling, and ongoing maintenance sessions for 4 years. 'Interventions designed to reduce hypertension included a weight loss component. Initial weight and weight losses are therefore lower. ''Interventions consisted of dietary counseling, behavior modification, support, cooking demonstrations, and nonsupervised exercise (walking).
360
TREATMENT O F ADULT O B E S I W
weight regain during the years following behavioral treatment. Nonetheless, the data show a m e a n net weight loss from baseline of 1.8 kg at follow-ups conducted on average 4.3 years after treatment. Several considerations must be taken into account in evaluating the long-term results of weight loss interventions. O n the one hand, long-term findings m a y display a favorable bias in that unsuccessful individuals are often less willing to participate in follow-up evaluations, and overweight subjects often obtain additional weight loss assistance during the course of follow-up (Wadden et al., 1989). O n the other hand, findings of smaU net losses or a return to baseline weights at long-term follow-up need to be viewed in the context of what might have happened if the obese individuals had never entered treatment (Brownell & Jeffery, 1987). For example, secular trend data from the Minnesota Heart Health Program (Shah, Hannan, & Jeffery, 1991) showed that over a 7-year period, m e n and w o m e n in the upper quartile of body mass index (BMI) experienced average weight gains of 2.6 and 5.7 kg, respectively. Such findings suggest that the natural course of obesity in untreated adults entails steady weight gain. Accordingly, a long-term finding of the maintenance of a small amount of weight loss m a y represent a relatively favorable outcome. In addition, m e a n weight changes provide only a partial view of long-term outcome. A reporting of categories of relative success m a y allow a fuller perspective of the degrees of partial success achieved by subsets of subjects (Wadden et al., 1997). For example, the Kramer and colleagues (1989) study reported an overall m e a n weight loss of 2.7 kg at a 4.5year foUow-up. However, an analysis by categories of relative success revealed that approximately 2 0 % of the subjects maintained losses of 5 kg or more, suggesting a notable degree of success for a significant number of individuals.
C O N T R I B U T O R S T O P O S H R E A T M E N T V^EIGHT G A I N
Poor maintenance of weight loss appears to result from a complex and variable intera of physiological, environmental, and psychological factors. Physiological factors, such as reduced metabolic rate (DuUoo & Jacquet, 1998; Ravussin & Swinburn, 1993), adaptive thermogenesis (Leibel, Rosenbaum, & Hirsch, 1995; Stock, 1999), and increased adipose tissue lipoprotein lipase activity (Kern, 1997; Kern, O n g , Saffari, & Carty, 1990), prime formerly obese individuals to regain lost weight. Continuous exposure to an environment rich in tasty, high-fat, high-calorie foods, combined with a dieting-induced heightened sensitivity to palatable foods, further predisposes these individuals to setbacks in dietary control (HiU & Peters, 1998; Rodin, Schank, & Streigel-Moore, 1989). M o s t overweight individuals experience difficulties coping with this unfriendly combination of environment and biology. Furthermore, during the period following weight loss treatment, there are fewer reinforcers to maintain adherence to changes in diet and activity (Wadden & BeU, 1990). T h e most rewarding element of treatment from the clients' perspective—namely, weight loss—typically ends with the cessation of active treatment. Consequently, m a n y individuals perceive a high behavioral "cost" associated with continued dietary control at the same time they are experiencing diminished "benefits" in terms of little or no additional weight loss. Thus discouragement is c o m m o n . Small posttreatment weight gains often lead to attributions of personal ineffectiveness that can trigger negative emotions and a sense of hopelessness, and sometimes even an abandonment of the weight control effort (Goodrick, Raynaud, Pace, & Foreyt, 1992; Jeffery, French, & Schmid, 1990).
Improving Maintenance of Weight Lost
361
MAINTENANCE STRATEGIES Providing strategies specifically designed to maintain the changes accomplished in inhial treatment m a y improve long-term outcome. M a n y different approaches have been evaluated, including extended treatment, relapse prevention training, monetary incentives, food provision, telephone prompts, peer support, exercise/physical activity, and multicomponent posttreatment programs.
Extended Treatment Improving the long-term effects of behavioral treatment involves finding ways to assist clients in sustaining key changes in the behaviors that regulate energy balance and weight loss. Various approaches to improving long-term outcome have been suggested by empirical observations, by theoretical models of the maintenance of behavior change, and by clinical pragmatism. For example, in a quantitative review of the behavioral treatment literature, Bennett (1986) observed that duration of treatment was the most important factor associated with weight loss. F r o m a conceptual perspective, continued treatment provides the opportunity for continued reinforcement of adherence to the behaviors needed for negative energy balance (Perri et al., 1992). F r o m a pragmatic viewpoint, extending the length of treatment offers a relatively simple clinical approach to improving outcome. Thus Perri, Nezu, Patti, and M c C a n n (1989) tested whether extending treatment would improve adherence and weight loss by comparing a standard 20-week program with an extended 40-week program. The results showed that the extended program significantly improved outcome compared to the standard treatment, even though treatment content was identical in both programs. Clients in extended treatment increased their weight losses by 3 5 % during the period from week 20 to week 40. Moreover, both weight loss and adherence data supported the hypothesis that the longer clients are in treatment, the longer they will adhere to the behaviors necessary for weight loss. However, follow-up data showed that after the extended treatment was concluded, clients reduced their adherence and began to regain weight. Table 17.2 presents the results of 13 studies in which behavioral treatment was extended beyond 6 months through the use of weekly or biweekly treatment sessions (Jakicic, Winters, Lang, &c Wing, 1999; Leermakers, Perri, Shigaki, & FuUer, 1999; Perri, Martin, Leermakers, Sears, & Notelovitz, 1997; Perri et al., 1987, 1988, 1989; Viegener et al., 1990; W a d d e n , Foster, & Letizia, 1994; W a d d e n et al., 1997; W a d d e n , Vogt, Foster, & Anderson, 1998; Weinstock, Dai, & W a d d e n , 1998; Wing, Blak, Marcus, Epstein, & Harvey, 1994; Wing, Venditti, Jakicic, PoUey, & Lang, 1998). Treatment in the 18 extended-intervention groups in these 13 studies included on average 40.8 sessions (range = 30-65) over the course of 40-78 weeks ( M - 54.1 weeks). At the conclusion of the extended-treatment period (approximately 12.5 months after the initiation of treatment), those groups that received behavior therapy with extended contact demonstrated m e a n net weight losses of 10.3 kg, maintaining 9 6 . 3 % of the 10.7 kg they had lost during the initial treatment period or during thefirst6 months of intervention. The inclusion of a control group (i.e., behavioral treatment without extended contact) in three of the studies (Perri et al., 1987, 1988, 1989) allows a rough comparison between groups receiving the same initial course of behavioral treatment (20 weekly group sessions) with and without extended therapist contacts. In these studies, the three groups that received behavior therapy without extended contact had a m e a n initial loss of 10 kg. At the point in time comparable to the conclusion of extended treatment, these standard-length
T A B L E 17.2. Response to Behavior Therapy for Obesity with Extended Contact (Weekly or Biweekly Sessions beyond 6 Months)
CJ CK
Initial tx. length (wk)
Mean initial wt. (kg)
Mean initial wt. loss (kg)
Type& no. of extendedcontact sessions
Length of extendedcontact period (wk)
Net loss after extended contact (kg)
Study
n
Perri et al. (1987)
16 27
20 20
88.1 89.8
10.3 10.7
0 15 bw
30
7.8" 11.5*'
Perri et al. (1988)
16 19
20 20
89.0 96.5
10.8 13.2
0 26 bw
52
5.7" 12.9^
Perri et al. (1989)
16 16
20 20
96.6 100.4
8.9 10.1
0 20 wk
Viegener et al. (1990)
32
16
98.7
8.9
13 bw
20 26
W a d d e n et al. (1994)
16
16
105.4
11.9
26 wk + 13 bw
Wing et al. (1994)
41
16
107.7
13.5
Perri et al. (1997)
24 25
16 H 26 G
87.1 89.8
10.4 9.4
Add'l % initial loss maintained
f/u without contact (wk)
Net loss at f/u (kg)
% initial loss maintained
lOMC met at final f/u?
9.0
76% 107% 53% 98% 71% 135% 101%
None
—
30% 60% 33% 86% 52% 98% —
52
12.2
103%
None
—
—
—
26 wk
26
10.5
78%
52
5.7
42%
Yes
13 bw 13 bw
26 26
12.1" 8.1''
116% 86%
13 13
11.7" 7.01''
113% 75%
Yes Yes
6.4" 13.6*
48 48
3.1" 6.4''
26 26
3.6" 11.4''
32 32
4.6" 9.9''
No Yes No Yes No Yes
—
W a d d e n et al. (1997)
77
26"^
96
17.4
22 wk
22
15.6
90%
52
W a d d e n et al. (1998)
38
20"*
97.1
11.0
10 bw
20
12.4
113%
None
Wing et al. (1998)
37 40 45
26 D 26 DE
99.6 98.7
9.1 10.3
13 bw 13 bw
26 26
5.5 7.4
56% 72%
28=
96.9
13.8
10 bw
20
15.2
148
26 Lb 26 Sb 26 SbE
90 92
13 bw 13 bw 13 bw
94 94
26 26 26 26 26
7.0 5.7
26 EF 26 W F
8.2 7.5 9.3 9.6 8.7
Weinstock etal. (1998) CO Ov CO
Jakicic et al. (1999) Leermakers etal. (1999)
28 20
88.3
13 bw 13 bw
10.0
7.9 8.5
8.5
49%
Yes
52 52
2.1 2.5
23% 24%
No No
110%
48
10.0
72%
Yes
85% 76% 108% 82% 98%
26 26 26
5.8 3.7" 7.4*
71% 49% 80%
Yes No Yes
26 26
5.2 7.9
54%" 91%''
Yes Yes
Note, bw, biweekly; D, diet; E, exercise; W F , weight-focused; EF, exercise-focused; H, home-based exercise; G, group-based exercise; Lb, long-bout exercise; Sb, short-bout exercise; SbE, short-bout exercise with home equipment. Other abbreviations as in Table 17.1. "'''Means with differing superscripts indicate significant between-group differences [p < .05). 'Included short-term use of a low-calorie liquid diet (925 kcal/day). ''Included use of low-calorie (1,000 kcal/day) or balanced-deficit (1,200 kcal/day) diet.
364
TREATMENT O F ADULT OBESITY
groups had a mean net loss of 6.6 kg, maintaining about two-thirds (66.5%) of their inifial weight reduction. Thus judging the effects of the extended treatments by comparison with the standard-length groups suggests a beneficial impact for extended contact (i.e., 9 6 . 3 % vs. 6 6 . 5 % of initial loss maintained). O f the 13 studies listed in Table 17.2, 10 included additional foUow-up periods beyond the extended-treatment period. The results of these additional follow-up assessments conducted on average 2 2 months after initiation of treatment showed that the extended-treatment groups demonstrated m e a n net loss of 7.0 kg (65.8% of their initial reduction; range = 2 3 % - 1 1 3 % ) . In contrast, the three groups without extended contact maintained a mean net loss of 3.8 kg (38.3% of their initial reduction; range - 3 0 % - 5 2 % ) . At final follow-up, none of the three groups without extended contact met the l O M criterion for successful maintenance, whereas 12 of the 15 extended-treatment groups met or exceeded this criterion. Moreover, two of the three extended-treatment groups that failed to meet the l O M criterion were from one study (Wing et al., 1998). That study, conducted with diabetic patients, suffered from unusually low attendance rates ( 2 9 % ) , perhaps because of the large initial therapy group sizes (n s 20) and the requirement in the exercise condition that subjects complete a 50- to 60-minute walk as part of the treatment session. CoUectively, the data in Table 17.2 strongly suggest that extended treatment improves the maintenance of weight loss. Table 17.3 presents the results of randomized trials that evaluated various other strategies designed to enhance the long-term effect of behavioral weight loss treatment. Included in the table are studies with posttreatment foUow-up evaluations of 12 months or longer that tested maintenance procedures implemented (or continued) during the period following initial treatment.
Relapse Prevention Training Two studies have tested relapse prevention training (RPT), in which participants are taught h o w to avoid or cope with slips and relapses. Perri, Shapiro, Ludwig, Twentyman, and M c A d o o (1984) found that including R P T during the course of initial treatment was not effective, but that combining R P T with a multicomponent program of client-therapist contacts by mail and telephone significantly improved 