OVERWEIGHT AND THE METABOLIC SYNDROME: FROM BENCH TO BEDSIDE

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2 OVERWEIGHT AND THE METABOLIC SYNDROME: FROM BENCH TO BEDSIDE

3 ENDOCRINE UPDATES Shlomo Melmed, M.D., Series Editor J.A. Fagin (ed.): Thyroid Cancer ISBN: J.S. Adams and B.P. Lukert (eds.): Osteoporosis: Genetics, Prevention and Treatment ISBN: B.-Å. Bengtsson (ed.): Growth Hormone ISBN: C. Wang (ed.): Male Reproductive Function ISBN: B. Rapoport and S.M. McLachlan (eds.): Graves Disease: Pathogenesis and Treatment ISBN: W.W. de Herder (ed.): Functional and Morphological Imaging of the Endocrine System ISBN H.G. Burger (ed.): Sex Hormone Replacement Therapy ISBN A. Giustina (ed.): Growth Hormone and the Heart ISBN W.L. Lowe, Jr. (ed.): Genetics of Diabetes Mellitus ISBN J.F. Habener and M.A. Hussain (eds.): Molecular Basis of Pancreas Development and Function ISBN N. Horseman (ed.): Prolactin ISBN M. Castro (ed.): Transgenic Models in Endocrinology ISBN R. Bahn (ed.): Thyroid Eye Disease ISBN M.D. Bronstein (ed.): Pituitary Tumors in Pregnancy ISBN K. Sandberg and S.E. Mulroney (eds.): RNA Binding Proteins: New Concepts in Gene Regulation ISBN V. Goffin and P.A. Kelly (eds.): Hormone Signaling ISBN M.C. Sheppard and P.M. Stewart (eds.): Pituitary Disease ISBN N. Chattopadhyay and E.M. Brown (eds.): Calcium-Sensing Receptor ISBN H. Vaudry and A. Arimura (eds.): Pituitary Adenylate Cyclase- Activating Polypeptide ISBN R.C. Gaillard (ed.): The ACTH AXIS: Pathogenesis, Diagnosis and Treatment ISBN P. Beck-Peccoz (ed.): Syndromes of Hormone Resistance on the Hypothalamic- Pituitary-Thyroid Axis ISBN E. Ghigo (ed.): Ghrelin ISBN X C.B. Srikant (ed.): Somatostatin ISBN V.D. Castracane and M.C. Henson (eds.): Leptin ISBN G.A. Bray and D.H. Ryan (eds.): Overweight and the Metabolic Syndrome ISBN

4 OVERWEIGHT AND THE METABOLIC SYNDROME: FROM BENCH TO BEDSIDE Edited by George A. Bray, MD Pennington Biomedical Research Center Louisiana State University System Baton Rouge, Louisiana, USA Donna H. Ryan, MD Pennington Biomedical Research Center Louisiana State University System Baton Rouge, Louisiana,USA

5 George A. Bray, MD Donna H. Ryan, MD Pennington Biomedical Research Center Pennington Biomedical Research Center Louisiana State University Louisiana State University 6400 Perkins Road 6400 Perkins Road Baton Rouge, LA, USA Baton Rouge, LA, USA OVERWEIGHT AND THE METABOLIC SYNDROME: FROM BENCH TO BEDSIDE Library of Congress Control Number: ISBN-10: e-isbn-10: ISBN-13: e-isbn-13: Printed on acid-free paper Springer Science+Business Media, LLC All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, Inc., 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed in the United States of America springer.com

6 Contents Preface Contributors xv xix Chapter 1: Neuroendocrine Control of Food Intake Andrew A. Butler, James L. Trevaskis and Christopher D. Morrison 1 1. Introduction 1 2. Central Nervous System Regulation of Feeding Behavior 2 3. Neuroendocrine Factors Secreted from the Gut Cholecystokinin Peptide YY Ghrelin Amylin Enterostatin Glucagon-like Peptide Bombesin Family: Bombesin, Gastrin-releasing Peptide and Neuromedin B Oxyntomodulin Leptin Neuroendocrine Indicators of Long-term Energy Balance: Leptin and Insulin Leptin and Insulin Signaling in Diet-induced Obesity Summary 13 References 13 Chapter 2: Body Composition Assessment of Obesity Wm. Cameron Chumlea Introduction Overview of Body Composition Methods Anthropometry Weight and Stature Body Mass Index Abdominal Circumference Skinfolds Bioelectric Impedance Analysis 28

7 vi Contents 2.7. Body Density Total Body Water Dual-energy x-ray Absorptiometry Ethnic Differences in Body Composition Available Reference Data Recommendations Conclusion 31 Acknowledgments 32 References 32 Chapter 3: Prevalence of Obesity and the Metabolic Syndrome Ali H. Mokdad and Earl S. Ford Overweight and Obesity Prevention and Control Programs THE Metabolic Syndrome Preventive and Control Strategies Future Perspectives 48 References 49 Chapter 4: The Genetic Contribution to Obesity Raul A. Bastarrachea, Jack W. Kent Jr., Jeff T. Williams, Guowen Cai, Shelley A. Cole and Anthony G. Comuzzie Introduction Obesity as a Common Complex Phenotype Ancient Genes in a Modern World: An Evolutionary Genetic Perspective on Obesity Approaches to Obesity Gene Discovery Candidate Gene Association Study Genome Scan mrna Evidence from Animal Models for the Genetic Contribution to Obesity Monogenic Obesity Oligogenic Obesity Evidence for the Genetic Contribution to Obesity in Humans The Genetic Contribution to Rare Forms of Human Obesity Genetic Contribution to Common Human Obesity Conclusion 72 Acknowledgments 73 References 73

8 Contents vii Chapter 5: Etiology of Obesity: The Problem of Maintaining Energy Balance Barry E. Levin and Deborah J. Clegg Introduction: Obesity and the Concept of Defended Body Weight Neural Control of the Defended Body Weight Obesity and the Problem of Maintaining Body Weight How Is Body Weight Really Regulated? Factors That Lower the Defended Body Weight Implications for Future Research 91 References 92 Chapter 6: Current Views of the Fat Cell as an Endocrine Cell: Lipotoxicity Tamara Tchkonia, Barbara E. Corkey and James L. Kirkland Introduction Functions of Fat Tissue Conditions Associated with Lipotoxicity Mechanisms of Lipotoxicity Inherent Properties of Cells Contribute to Susceptibility to Lipotoxicity Association between Lipids and Inflammatory Responses Mechanisms of Defense against Lipotoxicity Preadipocytes and Fat Cells Are more Resistant than Other Cell Types to FA Summary Conclusions 117 Acknowledgments 118 References 118 Chapter 7: Ectopic Fat and the Metabolic Syndrome Frederico G.S. Toledo and David E. Kelley Introduction Consequences of Excess Adiposity to Whole-body Glucose Homeostasis FFA-induced Insulin Resistance Ectopic Fat in Skeletal Muscle and Insulin Resistance Relationships between Ectopic Fat in Liver and Insulin Resistance Human Lipodystrophic Syndromes Concluding Remarks 131 References 132 Chapter 8: Abdominal Obesity and the Metabolic Syndrome Jean-Pierre Després, Isabelle Lemieux and Natalie Alméras Introduction Metabolic Syndrome without Hyperglycemia Predicts an Inreased CHD Risk 140

9 viii Contents 3. Why Measure Waist Circumference as well and not just BMI? Abdominal Obesity: The Driving Force behind the Metabolic Syndrome? The Metabolic Syndrome: Is Waist Girth Sufficient? Are NCEP-ATP III Criteria Valid in All Populations? Managing CHD Risk in Patients with the Metabolic Syndrome: What Should Be Our Goal? Summary 146 Acknowledgments 148 References 148 Chapter 9: The Problems of Childhood Obesity and the Metabolic Syndrome Sonia Caprio and Ram Weiss Introduction Prevalence of the Metabolic Syndrome in Children and Adolescents: Impact of Obesity Effects of Insulin Resistance (HOMA-IR) on the Prevalence of the Metabolic Syndrome Proinflammatory and Antiinflammatory Markers and Insulin Resistance Pathophysiological Studies of the Prediabetic Phenotype in Youth Relationship between Insulin Resistance and Tissue Lipid Partitioning Early Reduction of β-cell Sensitivity to Glucose in Obese Youth with Impaired Glucose Tolerance Longitudinal Study of Changes in Glucose Tolerance Status in Obese Youth 164 Acknowledgments 165 References 165 Chapter 10: Evaluation of the Overweight and Obese Patient George A. Bray and Donna H. Ryan Introduction Definitions Anthropometric Measures Height and Weight Waist Circumference Instrumental Methods for Measuring Body Fat Dual X-ray Absorptiometry Density Isotope Dilution Bioelectric Impedance Imaging Techniques for Body Composition Summary of Clinical Recommendations for Measurement of Body Composition Body Fat through the Life Span Prevalence of Overweight 174

10 Contents ix 9. Clinical Evaluation of Overweight Patients Body Mass Index Waist Circumference Weight Gain Sedentary Lifestyle Laboratory and Other Measures The Metabolic Syndrome Etiologic Factors Underlying Obesity Introduction to Treatment: Risk Benefit Assessment Conclusion 183 References 184 Chapter 11: Dietary Approaches to Obesity and the Metabolic Syndrome Gary D. Foster and Angela P. Makris Introduction Low-fat Diets Efficacy of Low-fat Diets on Weight Loss, Hypertension, and Diabetes Very-low-fat Diets Efficacy of Very-low-fat Diets on Weight Loss and Cardiovascular Disease Moderate-fat Diets Efficacy of Moderate-fat Diets on Weight Loss, Cardiovascular Disease, and Diabetes The High-protein Diet Efficacy of High-protein Diets on Weight Loss Low-carbohydrate Diets Efficacy of Low-carbohydrate Diets on Weight Loss, Insulin Sensitivity, and Lipids Low Glycemic Index Diet Effects of Low Glycemic Index Diets on Hunger and Weight Loss and Insulin Sensitivity Clinical Implications and Future Directions for Research 205 References 205 Chapter 12: Exercise as an Approach to Obesity and the Metabolic Syndrome John M. Jakicic and Amy D. Otto Introduction Effect of Exercise on Health-related Parameters Impact of Exercise on Weight Loss Exercise Prescription Considerations for Long-term Weight Control Summary 216

11 x Contents Acknowledgments 216 References 216 Chapter 13: Behavioral Strategies for Controlling Obesity Donald A. Williamson, Corby K. Martin and Tiffany M. Stewart Introduction History of Behavioral Strategies for Controlling Obesity Philosophy of Treatment Behavioral Treatment for Adults Approach and Outcomes Duration of Treatment Targets and Tools Weight Maintenance Strategies Special Considerations Behavioral Treatment for Children and Adolescents Approaches, Tools, and Outcomes Reinforcement, Adherence, and Behavior Change Social Support and Parent Training Problem-solving Meal Planning Physical Activity Special Considerations Conclusions Summary 230 References 231 Chapter 14: Obesity Prevention Shiriki K. Kumanyika and Stephen R. Daniels Introduction Defining the Task Individual Level Perspective Population Perspective Goals and Priorities Population-wide Approaches Initiatives Related to Food Initiatives Related to Physical Activity Social Marketing Prevention Targeted to Selected Population Groups Adults Children Individually Targeted Approaches Multilevel Approaches 247

12 Contents xi 7. Methodological Considerations Conclusion 249 Note 249 References 249 Chapter 15: Orlistat and Sibutramine in the Management of Obesity Holly Wyatt Introduction Who Is Appropriate? Criteria for Use of Weight Loss Medications Why Do Health Care Providers Choose not to Use Weight Loss Medications? What Weight Loss Drugs Are Available? How Should Weight Loss in Medication Clinical Trials Be Evaluated? Sibutramine Mechanism of Action Therapeutic Potential for Obesity Efficacy in Weight Loss Maintenance Efficacy in Managing Obesity-related Risk Factors Tolerability and Safety Special Considerations when Prescribing Sibutramine Orlistat Mechanism of Action Therapeutic Potential for Obesity Efficacy in Weight Loss Maintenance Efficacy in Managing Obesity-related Risk Factors Tolerability and Safety Special Considerations when Prescribing Orlistat The Future of Weight Loss Medications Sibutramine and Orlistat Usage in Adolescents Combination Therapy Continuous vs. Episodic Medication Usage Summary 274 References 274 Chapter 16: A Status of Drugs on the Horizon for Obesity and the Metabolic Syndrome a Comprehensive Review 2005 Frank Greenway and George Bray Introduction Drugs Approved for Indications Other than Obesity and That Cause Weight Loss Bupropion Fluoxetine/Sertraline Zonisamide Topiramate 284

13 xii Contents 2.5. Metformin Somatostatin Pramlintide Exenatide Drugs in Phase III Clinical Trials with no Approval Rimonabant Axokine Leptin Drugs in the Early Phases of Development Growth Hormone Fragment Cholecystokinin PYY Oleoylestrone Serotonin 2C Receptor Agonist Neuropeptide Y Receptor Antagonists Melanin Concentrating Hormone Receptor-1 Antagonist Pancreatic Lipase Inhibitor Glucagon-like Peptide-1 Agonists and Dipeptidyl Peptidase-4 Inhibitors Drugs no Longer under Investigation or Withdrawn β3-adrenergic Agonists Ephedra Phenylpropanolamine Bromocriptine Ecopipam New Areas where Drugs Are Being Developed Histamine-3 Receptor Antagonists Ghrelin Antagonist β-hydroxysteroid Dehydrogenase Type I Inhibitor Modulators of Energy Sensing in the Brain (Acetyl Co-A Carboxylase 2 Inhibitor; Fatty Acid Synthase; Carnitine Palmitoyltransferase-3) Adiponectin Melanocortin-4 Receptor (MC4R) Agonists Natural Products (over-the-counter Preparations) Chromium Garcinia cambogia Chitosan Hoodia Stevia Citrus aurantium Summary and Conclusions 299 References 300

14 Contents xiii Chapter 17: Surgical Treatment of the Overweight Patient George A. Bray Introduction Surgical Approaches to Obesity and Their Historical Context Indications and Contraindications Indications in Adults Contraindications for Adults Bariatric Surgery for the Pediatric Age Group Effectiveness of Surgical Procedures Mechanisms for Weight Loss Benefits from Bariatric Surgery Complications Associated with Bariatric Surgery Complications Following Lap-band Bariatric Surgery Complications Following Restrictive Bariatric Surgery Complications with Malabsorptive Operations Other Operative Procedures for the Overweight Patient Intragastric Balloon Gastric Stimulation or Gastric Pacing Liposuction and Omentectomy Summary 322 References 323 Index 329

15 Preface The field of obesity and the metabolic syndrome continues to advance on all fronts. This book is an effort to bring together a series of chapters that cover many of the newer facets of the problem. We have tried to capture the goal of this book in the subtitle from bench to bedside. Fundamentally, as human biologists, we are interested in understanding the problem of obesity and the metabolic syndrome and then applying this new knowledge to easing the burden of people afflicted in this disease state. We begin with the laboratory findings. Butler and his colleagues begin the process with an illuminating discussion of the factors that control the termination of meals. After a brief review of the neuroendocrine control system, they provide a detailed look at the gastrointestinal and pancreatic factors that can stimulate or inhibit food intake. They then look at the long-term control affected by leptin and insulin. In the next chapter, Dr. Chumlea discusses the various methods for measuring obesity. Dual-energy absorptiometry (DXA) has the ability to provide estimates of fat mass, lean mass and bone mass making it quite versatile. However, from a practical perspective, weight, waist circumference and the body mass index (body weight in kg divided by the square of height in meters) are the most useful. The body mass index (BMI) has been the most widely used index in the assessment of the current changes in prevalence of obesity, providing a good picture of the increasing epidemic of obesity. The progress of this epidemic has been well characterized by Dr. Mokdad from the Centers for Disease Control and Prevention, the U.S. Governmental agency charged with tracking this epidemic. Genetic factors are clearly behind the susceptibility to obesity that characterizes this epidemic. Dr. Comuzzie, who has contributed important information to this problem, focuses on the advances that we have experienced in understanding the relations of nature and nurture. In a well written and timely chapter, Drs. Levin and Clegg argue the case of a set-point or a defended body weight. They begin with the historical and anatomic data and the move to discussing the intricacies of the mechanisms that control this process. Fat is the site for storage of extra energy. When the fat cells reach their maximum storage capacity, new fat cells may be recruited, but fat may also be stored ectopically in other organs. Tchkonia, Corkey, Kirkland explore this important new concept in a chapter dealing with lipotoxicity. The conditions for lipotoxicity occur when net capacity to store and utilize lipids is exceeded in diseases