Series Editor: Leonid PoretskyContemporary Endocrinology

Michael S. Freemark Editor

Pediatric ObesityEtiology, Pathogenesis and Treatment

Second Edition

Contemporary EndocrinologySeries Editor:Leonid Poretsky

Division of Endocrinology

Lenox Hill Hospital

New York, NY, USA

More information about this series at http://www.springer.com/series/7680

Michael S. FreemarkEditor

Pediatric Obesity

Etiology, Pathogenesis and Treatment

Second Edition

Contemporary EndocrinologyISBN 978-3-319-68191-7 ISBN 978-3-319-68192-4 (eBook)https://doi.org/10.1007/978-3-319-68192-4

Library of Congress Control Number: 2017962621

1st edition: © Springer Science+Business Media, LLC 2010

2nd edition: © Springer International Publishing AG 2018

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or

part of the material is concerned, specifically the rights of translation, reprinting, reuse of

illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,

and transmission or information storage and retrieval, electronic adaptation, computer software,

or by similar or dissimilar methodology now known or hereafter developed.

The use of general descriptive names, registered names, trademarks, service marks, etc. in this

publication does not imply, even in the absence of a specific statement, that such names are

exempt from the relevant protective laws and regulations and therefore free for general use.

The publisher, the authors and the editors are safe to assume that the advice and information in

this book are believed to be true and accurate at the date of publication. Neither the publisher nor

the authors or the editors give a warranty, express or implied, with respect to the material

contained herein or for any errors or omissions that may have been made. The publisher remains

neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Printed on acid-free paper

This Humana Press imprint is published by Springer Nature

The registered company is Springer International Publishing AG

The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

EditorMichael S. FreemarkDuke University School of Medicine Durham, NC USA

To my Duke colleagues, who fostered my intellectual development and enriched my academic career, and to my wife, Anne Slifkin, who provided incisive critiques of portions of the narrative and who remains my best friend and loving partner in life

vii

As obesity among adults has reached epidemic proportions around the world

(affecting, for example, 1/3 of the US adult population) [1], it is becoming

clear that the roots of adult obesity are often found in childhood. With atten-

tion to detail characteristic of pediatricians, Dr. Michael Freemark and an

illustrious group of authors have produced a second edition of the volume

devoted to childhood obesity that is unique in its scope and clarity of presen-

tation. The authors cover extensively both genetic and environmental factors

that lead to pediatric obesity, including its monogenetic and syndromic forms.

In addition to posing risks for children’s health, childhood obesity

increases the risk of adult obesity. The recent statement by the Endocrine

Society [2] indicates that treating adult obesity with lifestyle intervention is

an extremely difficult and only minimally successful effort. Prevention of

obesity, therefore, should begin in childhood.

Managing obesity requires deep understanding of its biology. In this

regard, the monograph edited by Freemark is an invaluable tool for all those

involved in preventing and treating obesity, whether in individual patients or

in public health programs. This book is highly recommended to a wide audi-

ence interested in containing the worldwide epidemic of metabolic disease.

References

1. NIH (National Institute of Diabetes and Digestive and Kidney Diseases).

Overweight and obesity statistics. https://www.niddk.nih.gov/health-

information/health-statistics//overweight-obesity.

2. Schwartz MW, et al. Obesity pathogenesis: an endocrine society scientific

statement. Endocrine Rev. 2017;38(4):267–96. https://doi.org/10.1210/

er.2017-00111.

New York, NY, USA Leonid Poretsky, MD

Series Editor Foreword

ix

The first edition of this textbook, published in 2010, described an evolving

epidemic of childhood obesity in the United States and other Western coun-

tries and the emergence in young people of serious comorbidities including

insulin resistance, type 2 diabetes mellitus, hyperlipidemia, fatty liver dis-

ease, hypertension, and the metabolic syndrome. During the past 7 years, the

worldwide prevalence of childhood obesity has soared, and the number of

American children with severe (Class III) obesity has increased by 40%, with

a predictable rise in the rates of life-threatening complications. The obesity

epidemic has inflated medical costs dramatically, limited human productivity,

and reduced life expectancy.

This second edition embodies all of the strengths of the original book but

is deeper and broader in scope, with new chapters on emerging themes includ-

ing metabolomics, genomics, and the roles of gastrointestinal hormones, the

microbiome, brown adipose tissue, and endocrine disruptors in the pathogen-

esis of childhood obesity. Reviews of the effects of weight excess on cogni-

tive performance and immune function complement detailed analyses of the

biochemical and molecular pathways controlling the development of child-

hood adiposity and metabolic disease. Critical assessments of nutritional

interventions (including new chapters on infant feeding practices and vege-

tarian diets) and superb reviews of behavioral counseling, pharmacotherapy,

and bariatric surgery provide practical guidance for the management of over-

weight children. Penetrating analyses of the obesity epidemic in its social,

cultural, economic, and political contexts highlight challenges and opportuni-

ties for obesity prevention and community action. The perspective is interna-

tional in scope and reflects the expertise and experience of many of the

leading figures in the field.

Despite extensive investigations into the mechanisms controlling food

intake and weight gain, the precise roles of genetic and environmental factors

and of nutrient balance and energy expenditure in the development and main-

tenance of childhood obesity remain, surprisingly, obscure. As in the first

edition, I conclude each chapter with comments and questions for the authors

that highlight the limitations of our understanding and the need for additional

investigation. My premise is that better understanding of childhood obesity

and its comorbidities will yield new approaches to prevention and treatment.

It is this objective that I hope to achieve through the publication of this book.

Durham, NC Michael S. Freemark, MD

Preface to the Second Edition

The wise man says: I will eat to live, and the fool says: I will live to eat.

−Orchot Tzadikim, Germany, 15th century

To lengthen thy life, lessen thy meals.−Benjamin Franklin, Poor Richard’s Almanack, 1737

The rise of childhood obesity has placed the health of an entire generation at risk.

− Tom Vilsack, Huffington Post, 2010

xiii

Part I The Obesity Epidemic: A Global Perspective

1 Childhood Obesity in the Modern Age: Global Trends, Determinants, Complications, and Costs . . . . . . . . . . . . . . . . . . 3

Michael Freemark

Part II Hormonal and Metabolic Control of Appetite, Fat Deposition, and Energy Expenditure

2 Central Control of Energy Metabolism and Hypothalamic Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Belma Haliloglu and Abdullah Bereket

3 Gastrointestinal Hormones and the Control of Food Intake and Energy Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Laura C. Page, Mark D. Miller, David D’Alessio,

and Jenny Tong

4 The Gut Microbiome and Control of Weight Gain . . . . . . . . . . 63

Anita L. Kozyrskyj, Hein Min Tun, and Sarah L. Bridgman

Part III Adipocyte Development and Function in Obesity and Insulin Resistance

5 White Adipose Tissue Development and Function in Children and Adolescents: Preclinical Models . . . . . . . . . . . . 81

Pamela Fischer-Posovszky, Julian Roos, Verena Zoller,

and Martin Wabitsch

6 White Adipose Tissue Accumulation and Dysfunction in Children with Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

Antje Körner, Wieland Kiess, and Kathrin Landgraf

7 Brown Adipose Tissue and Body Weight Regulation . . . . . . . . . 117

Michael Freemark and Sheila Collins

Part IV The Genetics of Childhood Obesity

8 Monogenic Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

Marie Pigeyre and David Meyre

Contents

xiv

9 Syndromic Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

Krystal A. Irizarry and Andrea M. Haqq

10 Polygenic Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183

Anke Hinney and Johanna Giuranna

Part V Pre- and Peri-natal Determinants of Childhood Obesity

11 Maternal Determinants of Childhood Obesity: Maternal Obesity, Weight Gain and Smoking . . . . . . . . . . . . . . 205

Jenna Hollis, Hazel Inskip, and Siân Robinson

12 Fetal and Infancy Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

Ken K. Ong

13 Intrauterine Exposure to Maternal Diabetes and Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229

Dana Dabelea and Katherine A. Sauder

14 Endocrine Disruptors as Obesogens . . . . . . . . . . . . . . . . . . . . . . 243

Leonardo Trasande and Bruce Blumberg

Part VI The Roles of Diet and Energy Expenditure in Obesity Pathogenesis and Complications

15 Early Feeding Practices and Development of Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257

Megan H. Pesch and Julie C. Lumeng

16 Dietary Interventions in the Treatment of Paediatric Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

Megan L. Gow, Mandy Ho, Natalie B. Lister,

and Sarah P. Garnett

17 Vegetarian Diets and Pediatric Obesity . . . . . . . . . . . . . . . . . . . 287

Gina Segovia-Siapco, Sarah Jung, and Joan Sabaté

18 Energy Expenditure in Children: The Role of NEAT (Non-exercise Activity Thermogenesis) . . . . . . . . . . . . 305

Lorraine Lanningham-Foster and James A. Levine

Part VII Metabolic Complications of Childhood Obesity

19 Obesity and the Endocrine System, Part I: Pathogenesis of Weight Gain in Endocrine and Metabolic Disorders . . . . . . 323

Michael Freemark

20 Obesity and the Endocrine System, Part II: The Effects of Childhood Obesity on Growth and Bone Maturation, Thyroid and Adrenal Function, Sexual Development, and Bone Mineralization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333

Michael Freemark

Contents

xv

21 Metabolomic Signatures and Metabolic Complications in Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343

Pinar Gumus Balikcioglu and Christopher B. Newgard

22 Immune Function in Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363

Yazan Alwarawrah and Nancie J. MacIver

23 Pathogenesis of Insulin Resistance and Glucose Intolerance in Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . 379

Ram Weiss and Emilia Hagman

24 Youth-Onset Type 2 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393

Orit Pinhas-Hamiel, Philip S. Zeitler, and Megan M. Kelsey

25 Pathogenesis and Management of Dyslipidemia in Obese Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419

Brian W. McCrindle

26 Fatty Liver Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451

Della Corte Claudia, Antonella Mosca, Arianna Alterio,

Donatella Comparcola, Francesca Ferretti, and Valerio Nobili

27 Pathogenesis of Hypertension and Renal Disease in Obese Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463

Tracy E. Hunley, Vance L. Albaugh, and Valentina Kon

28 Sleep-Disordered Breathing and Sleep Duration in Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497

Annelies Van Eyck and Stijn Verhulst

29 Pediatric Metabolic Syndrome: Long-Term Risks for Type 2 Diabetes and Cardiovascular Disease . . . . . . . . . . . . . . . . . . . . . 511

Costan G. Magnussen, Brooklyn J. Fraser,

and Olli T. Raitakari

30 Childhood Obesity, Atherogenesis, and Adult Cardiovascular Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 527

Amy S. Shah and Elaine M. Urbina

31 Childhood Obesity and Cognitive Function . . . . . . . . . . . . . . . . 539

Dawn M. Eichen, Sara Appleton-Knapp,

and Kerri N. Boutelle

Part VIII Treatment of Childhood Obesity: Lifestyle Intervention

32 Family-Based Behavioral Interventions for Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555

Denise E. Wilfley and Katherine N. Balantekin

33 Exercise and Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . . 569

David Thivel, Grace O’Malley, and Julien Aucouturier

34 School- and Community-Based Interventions for Childhood Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589

Joel Gittelsohn and Sohyun Park

Contents

xvi

Part IX Pharmacotherapy and Bariatric Surgery for Obesity and Co-morbidities

35 Role of Pharmacotherapy in the Treatment of Pediatric Obesity and Its Comorbidities . . . . . . . . . . . . . . . . . . . . . . . . . . . 613

Aaron S. Kelly and Claudia K. Fox

36 Pathogenesis and Management of Adiposity and Insulin Resistance in Polycystic Ovary Syndrome (PCOS) . . . . . . . . . . 629

Thomas M. Barber, Jalini Joharatnam, and Stephen Franks

37 Prevention and Treatment of Obesity and Metabolic Dysfunction in Children with Major Behavioral Disorders: Second- Generation Antipsychotics . . . . . . . . . . . . . . . . . . . . . . . 643

Gloria Reeves and Linmarie Sikich

38 Bariatric Surgery in Adolescents . . . . . . . . . . . . . . . . . . . . . . . . . 661

Daniel Relles and Jeffrey L. Zitsman

Part X Challenges to Long-Term Success

39 The Role of the Primary Care Provider in Long-Term Counseling: Establishing a Therapeutic Alliance with the Child and Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685

Sarah Armstrong, Joseph A. Jackson Jr.,

and Jessica Lyden Hoffman

40 The Sociocultural Context for Obesity Prevention and Treatment in Children and Adolescents: Influences of Ethnicity and Gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 695

Shiriki Kumanyika

Part XI The Future of Childhood Obesity in the Global Marketplace

41 Fast-Food Value Chains and Childhood Obesity: A Global Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 717

Michelle Christian and Gary Gereffi

42 Why We Need Local, State, and National Policy-Based Approaches to Improve Children’s Nutrition in the United States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731

Megan Lott, Marlene Schwartz, Mary Story,

and Kelly D. Brownell

Appendix A: Valuable Reference Sites . . . . . . . . . . . . . . . . . . . . . . . . 757

Appendix B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759

Appendix C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761

Appendix D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 763

Contents

xvii

Appendix E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 765

Appendix F. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 767

Appendix G . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 793

Appendix H . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797

Contents

xix

Vance L. Albaugh, MD, PhD Section of Surgical Sciences, Department of

Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

Arianna Alterio, MD Hepatometabolic Unit, Bambino Gesù Children’s

Hospital, Rome, Italy

Yazan Alwarawrah, PhD Division of Pediatric Endocrinology and

Diabetes, Duke University, Durham, NC, USA

Sara Appleton-Knapp, PhD Department of Pediatrics, University of

California at San Diego, La Jolla, CA, USA

Sarah Armstrong, MD Department of Pediatrics, Duke University, Durham,

NC, USA

Department of Pediatrics, Duke Children’s Hospital and Health Center, Duke

University School of Medicine, Durham, NC, USA

Julien Aucouturier, PhD Department of Sport Sciences, Lille 2 University,

Ronchin, France

Katherine N. Balantekin, PhD, RD Department of Exercise and Nutrition

Sciences, University at Buffalo, New York, USA

Pinar Gumus Balikcioglu, MD Division of Pediatric Endocrinology and

Diabetes, Duke University Medical Center, Durham, NC, USA

Thomas M. Barber, MA, MBBS, MRCP, DPhil Clinical Sciences Research

Laboratories, University Hospitals Coventry and Warwickshire, Coventry,

West Midlands, UK

University of Warwick, Coventry, West Midlands, UK

Abdullah Bereket, MD Department of Pediatrics/Pediatric Endocrinology,

Marmara University, Fevzi Çakmak Mahallesi, Ustakaynarca-Pendik,

Istanbul, Turkey

Bruce Blumberg, PhD Department of Developmental and Cell Biology,

Department of Pharmaceutical Sciences, Department of Biomedical

Engineering, University of California at Irvine, Irvine, CA, USA

Kerri N. Boutelle, PhD Department of Pediatrics, University of California

at San Diego, La Jolla, CA, USA

Contributors

xx

Sarah L. Bridgman, BSc Department of Pediatrics, Edmonton Clinical

Health Academy, University of Alberta, Edmonton, AB, Canada

Kelly D. Brownell, PhD Sanford School of Public Policy, Duke University,

Durham, NC, USA

Michelle Christian, PhD Department of Sociology, University of Tennessee

at Knoxville, Knoxville, TN, USA

Sheila Collins, PhD Department of Integrative Metabolism, Sanford

Burnham Prebys Medical Discovery Institute, Orlando, FL, USA

Donatella Comparcola, MD Hepatometabolic Unit, Bambino Gesù

Children’s Hospital, Rome, Italy

Della Corte Claudia, MD Hepatometabolic Unit, Bambino Gesù Children’s

Hospital, Rome, Italy

David D’Alessio, MD Division of Endocrinology, Duke University Medical

Center, Durham, NC, USA

Dana Dabelea, MD, PhD Department of Epidemiology and Pediatrics,

University of Colorado Anschutz Medical Campus, Aurora, CO, USA

Dawn M. Eichen, PhD Department of Pediatrics, University of California

at San Diego, La Jolla, CA, USA

Annelies Van Eyck, PhD Department of Pediatrics, Antwerp University

Hospital, Edegem, Belgium

Laboratory of Experimental Medicine and Pediatrics, University of Antwerp,

Antwerp, Belgium

Francesca Ferretti, MD Hepatometabolic Unit, Bambino Gesù Children’s

Hospital, Rome, Italy

Pamela Fischer-Posovszky, PhD Division of Pediatric Endocrinology and

Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University

Medical Center, Ulm, Germany

Claudia K. Fox, MD, MPH Department of Pediatrics, Center for Pediatric

Obesity Medicine, University of Minnesota, Minneapolis, MN, USA

Stephen Franks, MD, FRCP, FMedSci St. Mary’s and Hammersmith

Hospitals, Imperial College Healthcare NHS Trust, Imperial College London,

London, UK

Department of Surgery and Cancer, Institute of Reproductive and

Developmental Biology, Imperial College London, London, UK

Brooklyn J. Fraser, BBiotech, MedRes (Hons) Menzies Institute for

Medical Research, University of Tasmania, Hobart, TAS, Australia

Michael Freemark, MD Division of Pediatric Endocrinology and Diabetes,

Duke University Medical Center, Durham, NC, USA

Contributors

xxi

Sarah P. Garnett, BSc, MNutDiet, PhD The Children’s Hospital at

Westmead, The Institute of Endocrinology and Diabetes, Westmead, NSW,

Australia

University of Sydney, Discipline of Paediatrics and Adolescent Health, The

Children’s Hospital at Westmead Clinical School, Westmead, NSW, Australia

Gary Gereffi, BA, MPhil, PhD Department of Sociology, Duke University,

Durham, NC, USA

Joel Gittelsohn, PhD Department of International Health, Bloomberg

School of Public Health, Johns Hopkins University, Baltimore, MD, USA

Johanna Giuranna, MSc Department of Child and Adolescent Psychiatry

and Psychotherapy, University of Duisburg-Essen, University Hospital Essen,

Essen, Germany

Megan L. Gow, BSc, BApplSc, PhD The Children’s Hospital at Westmead,

The Institute of Endocrinology and Diabetes, Westmead, NSW, Australia

Emilia Hagman, MSci, PhD Department of Human Metabolism and

Nutrition, Braun School of Public Health, The Hebrew University of

Jerusalem, Jerusalem, Israel

Department of Clinical Science, Intervention, and Technology, Karolinska

Institutet, NOVUM, Stockholm, Sweden

Belma Haliloglu, MD Department of Pediatrics/Pediatric Endocrinology,

Yeditepe University, Içerenköy, Yeditepe Unv. Hst., Haliloglu, Istanbul,

Turkey

Andrea M. Haqq, MD, MHS Department of Pediatrics, University of

Alberta, 1C4 Walter C. Mackenzie Health Sciences Center, Edmonton, AB,

Canada

Anke Hinney, MD Department of Child and Adolescent Psychiatry and

Psychotherapy, University of Duisburg-Essen, University Hospital Essen,

Essen, Germany

Mandy Ho, BN, MSc, PhD The University of Hong Kong, School of

Nursing, Pok Fu Lam, Hong Kong

Jessica Lyden Hoffman, BS Department of Pediatrics, Duke Children’s

Hospital and Health Center, Duke University School of Medicine, Durham,

NC, USA

Jenna Hollis, BNutrDiet, PhD University of Southampton, Southampton

General Hospital, MRC Lifecourse Epidemiology Unit, Southampton, UK

Tracy E. Hunley, MD Division of Nephrology and Hypertension,

Department of Pediatrics, Vanderbilt University Medical Center, Monroe

Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN, USA

Hazel Inskip, MSc, PhD, FFHP University of Southampton, Southampton

General Hospital, MRC Lifecourse Epidemiology Unit, Southampton, UK

Contributors

xxii

Krystal A. Irizarry, MD Department of Pediatrics, University of Rochester

Medical Center, Rochester, NY, USA

Joseph A. Jackson Jr., MD Department of Pediatrics, Duke University,

Durham, NC, USA

Jalini Joharatnam, MBBS, PhD New QEII Hospital, East and North

Hertfordshire NHS Trust, Welwyn Garden City, Hertfordshire, UK

Sarah Jung, MA, MS Loma Linda University, School of Public Health,

Center for Nutrition, Healthy Lifestyle, and Disease Prevention, Loma Linda,

CA, USA

Aaron S. Kelly, PhD Department of Pediatrics, Center for Pediatric Obesity

Medicine, University of Minnesota, Minneapolis, MN, USA

Megan M. Kelsey, MD, MS Department of Pediatrics, University of

Colorado School of Medicine, Aurora, CO, USA

Department of Endocrinology, Children’s Hospital Colorado, Aurora, CO,

USA

Wieland Kiess, MD Department of Women’s and Children’s Health, Center

for Pediatric Research, Hospital for Children and Adolescents of Leipzig

University, Leipzig, Germany

Valentina Kon, MD Division of Nephrology and Hypertension, Department

of Pediatrics, Vanderbilt University Medical Center, Monroe J. Carel Jr.

Children’s Hospital at Vanderbilt, Nashville, TN, USA

Antje Körner, MD Department of Women’s and Children’s Health, Center

for Pediatric Research, Hospital for Children and Adolescents of Leipzig

University, Leipzig, Germany

Anita L. Kozyrskyj, PhD Department of Pediatrics, Edmonton Clinical

Health Academy, University of Alberta, Edmonton, AB, Canada

Shiriki Kumanyika, PhD, MPH Department of Community Health and

Prevention, Dana and David Dornsife School of Public Health, Drexel

University, Philadelphia, PA, USA

Kathrin Landgraf, PhD Department of Women’s and Children’s Health,

Center for Pediatric Research, Hospital for Children and Adolescents of

Leipzig University, Leipzig, Germany

Lorraine Lanningham-Foster, PhD Department of Food Science and

Human Nutrition, Iowa State University, Ames, IA, USA

James A. Levine, MD, PhD Department for Obesity Solutions Mayo Clinic

and Arizona State University, Scottsdale, AZ, USA

Natalie B. Lister, MNutriDiet, PhD The Children’s Hospital at Westmead,

Institute of Endocrinology and Diabetes, Westmead, NSW, Australia

University of Sydney, Discipline of Paediatrics and Adolescent Health, The

Children’s Hospital at Westmead Clinical School, Westmead, NSW, Australia

Contributors

xxiii

Megan Lott, MPH, RD Duke Global Health Institute, Duke University,

Durham, NC, USA

Julie C. Lumeng, MD Division of Developmental and Behavioral Pediatrics,

Department of Pediatrics and Communicable Diseases, University of

Michigan, Ann Arbor, MI, USA

Nancie J. MacIver, MD, PhD Division of Pediatric Endocrinology and

Diabetes and the Departments of Pediatrics, Immunology, and Pharmacology

and Cancer Biology, Duke University School of Medicine, Durham, NC,

USA

Costan G. Magnussen, BHM, PhD Menzies Institute for Medical Research,

University of Tasmania, Hobart, TAS, Australia

Brian W. McCrindle, MD, MPH Department of Pediatrics, University of

Toronto, Toronto, ON, Canada

Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON,

Canada

David Meyre, PhD Department of Health Research Methods, Evidence, and

Impact, McMaster University, Hamilton, ON, Canada

Department of Pathology and Molecular Medicine, McMaster University,

Hamilton, ON, Canada

Mark D. Miller, MD Department of Pediatrics, Children’s Hospital of

Illinois, Peoria, IL, USA

Antonella Mosca, MD Hepatometabolic Unit, Bambino Gesù Children’s

Hospital, Rome, Italy

Christopher B. Newgard, PhD Departments of Medicine and Pharmacology

and Cancer Biology, Duke University Medical Center, Durham, NC, USA

Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular

Physiology Institute, Duke University Medical Center, Durham, NC, USA

Valerio Nobili, MD Hepatometabolic Unit Bambino Gesù Children’s

Hospital, Rome, Italy

Department of Pediatrics, Sapienza University, Rome, Italy

Grace O’Malley, PhD, MSc, BSc, Physio Department of Physiotherapy,

Children’s University Hospital, Dublin, Ireland

Ken K. Ong, MB, BChir, PhD MRC Epidemiology Unit and Department of

Paediatrics, University of Cambridge, Institute of Metabolic Science,

Cambridge, UK

Laura C. Page, MD Division of Pediatric Endocrinology and Diabetes,

Duke University Medical Center, Durham, NC, USA

Sohyun Park, PhD Department of Food Science and Nutrition, Hallym

University, Chuncheon, Gangwon, Republic of Korea

Contributors

xxiv

Megan H. Pesch, MD, MS Division of Developmental and Behavioral

Pediatrics, Department of Pediatrics and Communicable Diseases, University

of Michigan, Ann Arbor, MI, USA

Marie Pigeyre, MD, PhD Department of Health Research Methods,

Evidence, and Impact, McMaster University, Hamilton, ON, Canada

Department of Pathology and Molecular Medicine, McMaster University,

Hamilton, ON, Canada

Orit Pinhas-Hamiel, MD Pediatric Endocrine and Diabetes Unit, Edmond

and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat-Gan, Israel

Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Olli T. Raitakari, MD, PhD Research Centre of Applied and Preventive

Cardiovascular Medicine, University of Turku, Turku, Finland

Gloria Reeves, MD Department of Psychiatry, University of Maryland

School of Medicine, Baltimore, MD, USA

Daniel Relles, MD Department of Surgery, Lehigh Valley Children’s

Hospital, Allentown, PA, USA

Siân Robinson, BSc, PhD University of Southampton, Southampton

General Hospital, MRC Lifecourse Epidemiology Unit, Southampton, UK

NIHR Southampton Biomedical Research Centre, Southampton General

Hospital, Southampton, UK

Julian Roos, PhD student Division of Pediatric Endocrinology and

Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University

Medical Center, Ulm, Germany

Joan Sabaté, MD, DrPH Loma Linda University, School of Public Health,

Center for Nutrition, Healthy Lifestyle, and Disease Prevention, Loma Linda,

CA, USA

Katherine A. Sauder, PhD Department of Pediatrics, University of

Colorado Anschutz Medical Campus, Aurora, CO, USA

Marlene Schwartz, PhD Rudd Center for Food Policy and Obesity,

University of Connecticut, Hartford, CT, USA

Gina Segovia-Siapco, DrPH, MPH Loma Linda University, School of

Public Health, Center for Nutrition, Health Lifestyle, and Disease Prevention,

Loma Linda, CA, USA

Amy S. Shah, MD, MS Department of Pediatrics, Cincinnati Children’s

Hospital Medical Center, The University of Cincinnati, Cincinnati, OH, USA

Linmarie Sikich, MD Department of Psychiatry, Duke University, Durham,

NC, USA

Mary Story, PhD, RD Department of Community and Family Medicine

and Global Health, Duke Global Health Institute, Duke University, Durham,

NC, USA

Contributors

xxv

David Thivel, PhD, HDR AME2P Laboratory, Metabolic Adaptations to

Exercise under Physiological and Pathological Conditions, Clermont

Auvergne University, Aubière, France

Jenny Tong, MD, MPH Duke Molecular Physiology Institute, Durham,

NC, USA

Leonardo Trasande, MD, MPP Department of Pediatrics, Environmental

Medicine, and Population Health, New York University School of Medicine,

New York, NY, USA

Hein Min Tun, BVSc, MSc, PhD Department of Pediatrics, Edmonton

Clinical Health Academy, University of Alberta, Edmonton, AB, Canada

Elaine M. Urbina, MD, MS Department of Pediatrics, Cincinnati Children’s

Hospital Medical Center, The University of Cincinnati, Cincinnati, OH, USA

Stijn Verhulst, MD, MSc, PhD Department of Pediatrics, Antwerp

University Hospital, Edegem, Belgium

Laboratory of Experimental Medicine and Pediatrics, University of Antwerp,

Antwerp, Belgium

Martin Wabitsch, PhD, MD Division of Pediatric Endocrinology and

Diabetes, Department of Pediatric and Adolescent Medicine, Ulm University

Medical Center, Ulm, Germany

Ram Weiss, MD, PhD Department of Human Metabolism and Nutrition,

Braun School of Public Health, The Hebrew University of Jerusalem,

Jerusalem, Israel

Rambam Medical Center, Ruth Rappaport Children’s Hospital, Haifa, Israel

Denise E. Wilfley, PhD Department of Psychiatry, Washington University

School of Medicine, St. Louis, MO, USA

Philip S. Zeitler, MD, PhD Department of Pediatrics, University of

Colorado School of Medicine, Aurora, CO, USA

Department of Endocrinology, Children’s Hospital Colorado, Aurora, CO, USA

Jeffrey L. Zitsman, MD Center for Adolescent Bariatric Surgery, Morgan

Stanley Children’s Hospital of New York Presbyterian, New York, NY, USA

Division of Pediatric Surgery, Department of Surgery, Columbia University

Medical Center, New York, NY, USA

Verena Zoller, PhD Division of Pediatric Endocrinology and Diabetes,

Department of Pediatrics and Adolescent Medicine, Ulm University Medical

Center, Ulm, Germany

Contributors

Part I

The Obesity Epidemic: A Global Perspective

3© Springer International Publishing AG 2018

M.S. Freemark (ed.), Pediatric Obesity, Contemporary Endocrinology,

https://doi.org/10.1007/978-3-319-68192-4_1

Childhood Obesity in the Modern Age: Global Trends, Determinants, Complications, and Costs

Michael Freemark

Introduction

The first edition of this textbook, published in

2010, described with concern an evolving epi-

demic of childhood obesity in the United States

and other Western countries and the emergence

in young people of serious comorbidities includ-

ing insulin resistance, type 2 diabetes mellitus,

hyperlipidemia, fatty liver disease, hypertension,

and metabolic syndrome. While the rate of increase in the overall prevalence of childhood

obesity in the developed world has slowed, we

are now witness to three ominous trends. First,

the prevalence of childhood obesity has increased

dramatically worldwide and now threatens even

the most impoverished of nations. Second, the

number of American children with the most

severe and recalcitrant forms of obesity (Classes

II and III) has increased progressively during the

past 10 years. Finally, the persistence of severe

obesity from childhood into adult life exacts a

social and psychological toll on the individual,

increases medical costs, limits productivity, and

reduces life expectancy [1] (Fig. 1.1) owing to

complications including myocardial infarction,

renal insufficiency, cirrhosis, and liver cancer.

Extensive investigations conducted since the

publication of the first edition have yielded new

insights into the mechanisms by which

M. Freemark, MD

Division of Pediatric Endocrinology and Diabetes,

Duke University Medical Center,

Durham, NC 27710, USA

e-mail: freem001@mc.duke.edu

1

8 Studies124

Participants1,206,420

Deaths42,531

HR per 5 unit1.52 (1.47, 1.56)

4

2

1

0.5

15 20 25 30

Mean body mass index (kg/m2)

Haz

ard

rat

io (

95%

CI)

35 40 45

Fig. 1.1 Body mass index and all-cause mortality (ages

35–49) in four continents. (From Global BMI Mortality

Collaboration. Body mass index and all-cause mortality:

individual-participant-data meta-analysis of 239 prospec-

tive studies in four continents. Lancet. 2016 Aug 20;

388(10046):776–86. http://www.thelancet.com/journals/

lancet/article/PIIS0140-6736(16)30175-1/fulltext)

4

hormonal and metabolic factors control food

intake and weight gain and have elucidated bio-

chemical and molecular pathways central to the

pathogenesis of childhood adiposity and meta-

bolic disease. Yet the precise roles of genetic

and environmental factors and of nutrient bal-

ance and energy expenditure in the develop-

ment and maintenance of childhood obesity

remain, surprisingly, obscure, increasing the

challenge of defining optimal approaches to

prevention and treatment.

Global Prevalence and Trends in Pediatric Obesity

The best estimates of global prevalence and

trends in childhood obesity come from the

Global Burden of Disease Study 2013 [2]. Data

were derived from multi-country screening pro-

grams, national health ministry websites and

surveys, a systematic literature review, and

three large databases (the World Health

Organization (WHO) Global Infobase, the

International Association for the Study of

Obesity Data Portal, and the Global Health Data

Exchange).

Between 1980 and 2013, the worldwide prev-

alence of childhood overweight and obesity is

estimated to have risen 47.1% (Fig. 1.2). In

developed countries, the combined prevalence of

overweight and obesity has increased from

~16.9% in boys and 16.2% in girls in 1980 to

23.8% in boys and 22.6% in girls in 2013. Similar

trends, though lower absolute prevalence rates,

are noted in low-income, developing countries

(from ~8% in 1980 to ~13% in 2013). Rates of

obesity in adults have also increased over time in

developing as well as developed nations,

As a percentage of the population, childhood

obesity is most prevalent in the Pacific Islands

and Micronesia (>30%), the Caribbean, the

Middle East, and North Africa. In contrast, prev-

alence rates are low in parts of Southeast Asia

and Africa, including Bangladesh, Cambodia,

Eritrea, Ethiopia, Laos, Nepal, North Korea,

Tanzania, and Togo. Between 1980 and 2013,

rates of obesity have risen most dramatically in

Egypt, Saudi Arabia, Oman, Honduras, Bahrain,

New Zealand, Kuwait, and the United States.

Overweight and Obese

25

20

Pre

vale

nce

(%)

Pre

vale

nce

(%)

15

10

5

25

20

15

10

5

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

2012

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

2012

Year Year

Obese

Developed, Females

Developed, Males

Developing, Females

Developing, Males

Global, Females

Global, Males

Fig. 1.2 Global prevalence of overweight and obesity in

children and adults during 1980–2013. (Used with per-

mission of Elsevier from Ng M, Fleming T, Robinson M,

Thomson B, Graetz N, Margono C, et al. Global, regional,

and national prevalence of overweight and obesity in chil-

dren and adults during 1980–2013: a systematic analysis

for the Global Burden of Disease Study 2013. Lancet.

2014 Aug 30;384(9945):766–81)

M. Freemark

5

The Relationship Between National Income, Socioeconomic Development, and Childhood Obesity Rates

The emergence of childhood and adult obesity in

the developing world is the focus of ISCOLE (the

International Study of Childhood Obesity,

Lifestyle and the Environment), a cross-sectional

analysis [3] of 7341 children (age 9–11 years) in

urban and suburban centers throughout the world.

Objective measurements of body mass index

(BMI) and body fat content were obtained

between 2011 and 2013 at sites with diverse lev-

els of income and socioeconomic and educational

development.

ISCOLE investigators find that BMIz, % body

fat, and rates of childhood obesity correlate posi-tively with income in nations with low indices of

“human development,” as measured by life

expectancy at birth, mean years of schooling,

expected years of schooling, and gross national

income per capita. Conversely, obesity levels cor-

relate negatively with income in nations with

high levels of “human development” (Fig. 1.3).

ISCOLE postulates a transition in the social pat-

terning of obesity, such that people with higher

incomes in developing transitional societies

adopt lifestyles similar to those in developed

“Western” societies. Weight gain under these

conditions is valued as an indicator of newly

acquired affluence. Rates of obesity gradually

increase among those in lower socioeconomic

strata, as economic growth, technological

advances in food production, and penetration by

multinational food corporations reduce the rates

of famine and malnutrition while increasing the

availability of high-density vegetable oils and

simple sugars. In nations with high levels of

“human development,” people of means can par-

take of more nutritious (and costly) foods and

take advantage of leisure opportunities that

1.2a

b

0.8

0.4

0.0

A Boys

B Girls

-0.4

BM

I z-s

core

25%

22.5%

20%

17.5%

15%

Bod

y fa

t per

cent

age

1.2

0.8

0.4

0.0

Income 1

Low HDI

-0.4

BM

I z-s

core

25%

22.5%

20%

17.5%

15%

Bod

y fa

t per

cent

age

Income 2 Income 3 Income 4 Income 1

Mid HDI

Income 2 Income 3 Income 4 Income 1

High HDI

Income 2 Income 3 Income 4

Fig. 1.3 Relationships between national measures of

BMIz and % body fat in children and indices of “human

development.” (Used with permission of Nature

Publishing Group from Broyles ST, Denstel KD, Church

TS, Chaput JP, Fogelholm M, Hu G, et al., ISCOLE

Research Group. The epidemiological transition and the

global childhood obesity epidemic. Int J Obes Suppl.

2015 Dec;5(Suppl 2):S3–8)

1 Childhood Obesity in the Modern Age: Global Trends, Determinants, Complications, and Costs

6

promote energy expenditure. This serves to

reduce the risks of obesity among the more edu-

cated and professional classes.

Population Changes in the Relative Severity of Obesity

The acute and long-term risks of obesity depend

upon its severity as well as its duration. The

severity of obesity can be described as the rela-

tive degree to which the body mass index (BMI,

equals weight in kg divided by height in square

meters) exceeds the 95th percentile for age and

gender. Children with Class I obesity have BMIs

that equal or exceed the 95th percentile for age.

In Class II obesity, the BMI equals or exceeds

120% of the 95th percentile for age. BMI in Class III obesity equals or exceeds 140% of the 95th

percentile for age.

A review [4] of National Health and Nutrition

Examination Survey (NHANES) data found that

the percentage of American children with all

classes of obesity increased between 1999 and

2013–2014 (Fig. 1.4). The overall prevalence in

rates of Class II obesity increased from ~4% of

girls and boys in 1999 to 6.8% of girls and 5.8%

of boys in 2013–2014. Even higher rates were

recorded in adolescents; prevalence rose from 5.2

to 10.2% in teenage girls and from 6.0 to 8.9% in

teenage boys.

More severe Class III obesity rates increased

overall from 0.9 to 2.5% of American girls and

from 1.0 to 2.2% of American boys between

1999 and 2013–2014. Among adolescents, the

prevalence of Class III obesity increased from 1.7

to 4.9% of girls and from 1.6 to 3.7% of boys.

Although increasing rates of severe obesity

were noted in all racial and ethnic groups, the

prevalence of Class II and III obesity is highest

among black and Hispanic-American children.

Determinants of Childhood Obesity

Systematic literature reviews and meta-analyses

have identified a number of factors associated

with the development of childhood, adolescent,

and adult obesity [5–10] (Tables 1.1 and 1.2).

Among these, the most powerful determinants of

future obesity are maternal and paternal BMI,

which could reflect shared behaviors and envi-

ronmental stresses as well as genetic inheritance

[(see Chaps. 8 (Pigeyre/Meyre), 9 (Irizarry/

Haqq), and 10 (Hinney/Giuranna) on genetic

determinants of obesity]. Other major factors that

Fig. 1.4 Changes in the percentage of American children

with obesity increased between 1999 and 2013–2014.

Children with Class I obesity have BMIs that equal or

exceed the 95th percentile for age. In Class II obesity the

BMI equals or exceeds 120% of the 95th percentile for

age. BMI in Class III obesity equals or exceeds 140% of

the 95th percentile for age. (Used with permission of John

Wiley and Sons from Skinner AC, Perrin EM, Skelton

JA. Prevalence of obesity and severe obesity in US chil-

dren, 1999–2014. Obesity (Silver Spring). 2016 May;24

(5):1116–23)

Table 1.1 Factors that predispose to childhood obesity

1. Parental overweight or obesity

2. Ethnic heritage

3. Excess maternal gestational weight gain

4. Maternal smoking during pregnancy

5. Intrauterine exposure to maternal diabetes

6. High birth weight

7. Low birth weight with rapid catch-up weight gain

(early “adiposity rebound”)

8. Parental education and income (variable

depending upon the socioeconomic and cultural

milieu)

9. Formula (as opposed to breast) feeding

10. Caesarian section delivery

M. Freemark

7

predict the development of childhood obesity

include maternal gestational weight gain, smok-

ing during pregnancy, and birth weight.

Conversely, parental education and family

income correlate inversely with risks for child-

hood and adult obesity in the developed world.

Members of certain ethnic groups, including

African Americans, Hispanic Americans, Native

Americans, and Pacific Islanders, are prone to

excess weight gain; whether this reflects genetic,

environmental, social, and/or economic influ-

ences is currently unclear. Prolonged breastfeed-

ing reduces the risks of childhood obesity [10,

11]; this may be related in part to the relatively

low protein content of breast milk [12].

Conversely, Caesarian section delivery increased

slightly the risk of childhood obesity in some but

not all studies [13, 14].

Longitudinal studies of large cohorts in

Finland and the United Kingdom testify to the

power of these risk factors in predicting future

obesity in children. The Northern Finland Birth

Cohort [5] followed 4032 children from the

12th week of gestation through 16 years of age.

The risk of overweight and obesity at age

7–16 years correlated positively with prepreg-

nancy parental BMI, gestational weight gain,

maternal smoking during pregnancy, and birth

weight. In contrast, rates of childhood and ado-

lescent overweight and obesity correlated

inversely with parental (especially maternal)

professional status and number of household

members. These findings were validated in par-

allel studies of smaller cohorts in Veneto, Italy

(n = 1503) and Boston, Massachusetts (Project

Viva, n = 1032).

Findings similar to those in the Northern

Finland Birth Cohort were reported in the

Millennium Cohort (UK) Study [6], which ana-

lyzed rates of growth and weight gain in 13,513

healthy, singleton term infants from 9 through

37 months of age. In addition to parental BMI,

maternal smoking, birth weight (>3.5 kg), and

formula feeding, the investigators found that

rapid weight gain in infancy (>0.67 SD in weight

z during year 1) increased by fourfold the risk of

overweight at age 3.

Finally, an analysis [7] of 2119 Finnish chil-

dren (age 3–18 years) found that parental BMI

[odds ratio (OR) 1.57–1.64], birth weight (OR

1.16), and baseline childhood BMI (OR 2.51),

blood pressure (OR 1.42), and fasting insulin

(OR 1.51) correlated positively with the risk of

adult obesity, while family income (OR 0.83) and

parental education (OR 0.87) were negative

predictors.

Subsequent chapters in this book review in

greater detail the roles of maternal determinants

(Chap. 11 by Drs. Hollis, Inskip, and Robinson)

and early feeding practices (Chap. 15 by Drs.

Pesch and Lumeng) in the development of pedi-

atric obesity. It is critical to note that the various

risk factors appear to act in concert to determine

the odds of developing childhood obesity [5].

This is shown in Fig. 1.5, which demonstrates the

effects of various factor combinations on child-

hood obesity risk, and in a calculator that com-

bines various factors to estimate the risk of

childhood obesity in the three study cohorts

(Finnish, Veneto, and Project Viva). The calcula-

tor can be found in Data Set S2 at http://journals.

plos.org/plosone/article?id=10.1371%2Fjournal.

pone.0049919#s5.

Intrauterine Growth and the Development of Childhood Obesity

Birth weight has a Janus-like effect on future

obesity risk. Excess fetal weight gain in other-

wise healthy children predicts obesity more

strongly at age 3–13 years than at later stages of

life [5–7, 15–19]; on the other hand, fetal over-

growth in infants of diabetic mothers increases

the risks of future childhood, adolescent, and

Table 1.2 Medications that promote weight gain

Atypical (second-generation) antipsychotics

Glucocorticoids

Synthetic progestins

Hypoglycemic agents: insulin, sulfonylureas,

thiazolidinediones

Beta-blockers

Antidepressants: tricyclics, paroxetine, trazodone

Antiepileptics: valproate, gabapentin

1 Childhood Obesity in the Modern Age: Global Trends, Determinants, Complications, and Costs

8

adult obesity [19, 20]. This may reflect a pro-

gramming effect of fetal hyperinsulinemia on

adipogenesis and the propensity to store triglyc-

eride in white adipose tissue. The effects of

maternal obesity and gestational diabetes on

childhood weight gain are discussed in more

detail in Chap. 13 by Dana Dabelea and Katherine

Sauder.

Interestingly, low birth weight also increases

the risk of future obesity if accompanied by rapid

catch-up weight gain during the prepubertal years

[15, 16, 21, 22]. As shown in Fig. 1.6, catch-up

weight gain in former small for gestational age

(SGA) children is associated with visceral fat

deposition, insulin resistance, hyperinsulinemia,

and hypoadiponectinemia [23]. Similar effects

20

No gestational smokingBirth weight = 3 kgMaternal profession = professionalNumber of household members = 5

No gestational smokingBirth weight = 3.5 kgMaternal profession = skilled nonmanualNumber of household members = 4

History of gestational smokingBirth weight = 4 kgMaternal profession = skilled manualNumber of household members = 3

25

Paternal B

MI

30

35

0.13

20

0.32

0.79

1.93

0.79

35

1.93

4.61

10.62

0.44

30

1.07

2.58

6.12

0.24

25

Maternal BMI (kg/m2)

0.59

1.43

3.46

20

25

Paternal B

MI

30

35

0.51

20

1.26

3.03

7.14

3.03

35

7.14

15.91

31.76

1.69

30

4.05

9.41

20.34

0.93

25

Maternal BMI (kg/m2)

2.26

5.39

12.29

20

25

Paternal B

MI

30

35

3.59

20

8.39

18.39

35.66

18.39

35

35.66

57.69

77.03

11.01

30

23.33

42.80

64.79

6.36

25

Maternal BMI (kg/m2)

14.31

29.11

50.25

a b c

Fig. 1.5 Risk factors act in concert to determine the odds

of developing childhood obesity. (From Morandi A,

Meyre D, Lobbens S, Kleinman K, Kaakinen M, Rifas-

Shiman SL, et al. Estimation of newborn risk for child or

adolescent obesity: lessons from longitudinal birth

cohorts. PLoS One. 2012;7(11):e49919. http://journals.

plos.org/plosone/article?id=10.1371%2Fjournal.

pone.0049919#s5)

25

20

15

10

0

5Lea

n m

ass

(kg

)

2 4

Age (yr)6 8 2 4

Age (yr)6 8 2 4

Age (yr)6 8 2 4

Age (yr)6 8

12

9

6

3

0

Fat

mas

s (k

g)

4

3

2

†

1

0

Ab

do

min

al f

at (

kg)

60

40

20

0

Vis

cera

l fat

(cm

2 )

2

1

0

-1

-2

BM

I Z-s

core

10

8

6

2

4

0

Insu

lin (

mIU

/L)

300

200

100

0

IGF

-I (

ng

/mL

)

25

15

20

5

10

0HM

W a

dip

on

ecti

n (

mg

/L)

†

++

++

*

++

Fig. 1.6 Catch-up weight gain in former small for gesta-

tional age (SGA) children is associated with visceral fat

deposition, insulin resistance, hyperinsulinemia, and

hypoadiponectinemia. (Used with permission of Elsevier

from Ibáñez L, Lopez-Bermejo A, Diaz M, de Zegher

F. Catch-up growth in girls born small for gestational age

precedes childhood progression to high adiposity. Fertil

Steril. 2011 Jul;96(1):220–3)

M. Freemark

9

have been noted in infants and young children

recovering from acute and chronic malnutrition

[24]. In combination with increasing access to

high-density vegetable oils and free sugars [25–

27], the propensity of former SGA and malnour-

ished children to deposit fat in excess of lean body

mass may explain in part the dramatic increases in

rates of obesity and type 2 diabetes (see below) in

the developing world. A prime example is India

[28], which has high rates of intrauterine growth

restriction and childhood malnutrition and an

emerging epidemic of adult onset type 2 diabetes.

The effects of fetal growth restriction on child-

hood growth and weight gain are discussed in

more detail in Chap. 12 by Ken Ong.

The Adiposity Rebound

Following delivery of a healthy full-term infant,

there is an accumulation of body fat (see Appendix

Fig. 2) and an increase in BMI calculated as a

function of body length (from ~13–14 kg/M2 at

birth to ~17.3–18 kg/M2 at 5–9 months of age).

The magnitude and age at peak BMI in infancy

vary to some extent among ethnic groups [29]; in

part this might reflect population differences in

maternal nutritional status, birth weight, and infant

feeding practices (see Chaps. 11 and 15, by Hollis

and colleagues and Pesch and Lumeng, respec-

tively). Genetic determinants also likely play

important roles [30]. After peaking in infancy, the

BMI normally declines to a nadir at ~5–6 years

of age. Thereafter, the BMI “rebounds,” rising

progressively throughout late childhood and

adolescence.

Numerous studies demonstrate that the risk of

childhood obesity is higher in those with an ear-

lier and/or exaggerated “adiposity rebound” ([31,

32]; see also Chap. 6 by Dr. Korner and her col-

leagues). An early rebound is also associated

with earlier menarche in girls [33] and with

higher risks for obesity, glucose intolerance, and

the metabolic syndrome in adulthood [34–36].

As noted previously, the adiposity rebound

may in some cases reflect recovery from intra-

uterine and/or early postnatal malnutrition [31,

37]. In others, an excessive rebound results from

dietary indiscretion and/or sedentary behavior

(see below). Breastfeeding in infancy may delay

and reduce the magnitude of the adiposity

rebound [12, 31, 38]; some investigators postu-

late that the high fat/low protein content of breast

milk reduces circulating levels of insulin and

thereby limits adipogenesis and fat deposition

[12, 31, 37].

The Role of Energy Intake in the Development and Maintenance of Childhood Obesity

Many investigators ascribe the rise in childhood

obesity rates to increases in the intake of fast-

food and sugary beverages. Indeed, cross-

sectional studies show that intake of

sugar-sweetened beverages and high-fat foods is

associated with higher BMIz scores in children

[39–43]. However, direct evidence supporting the

nutrient hypothesis on a population scale is sur-

prisingly weak, in part because current measures

of population-wide caloric intake in children are

highly suspect and possibly invalid.

Trends in Population Food Intake and Availability

Most studies of caloric and macronutrient intake

in children are based on retrospective 24-hour dietary recalls performed once or twice in

national surveys. The reliability of dietary recalls

declines markedly as children enter adolescence;

moreover, overweight people are known to

underestimate (in some cases dramatically) their

intake of calories and foods known to be

obesogenic.

This might explain certain paradoxical find-

ings from studies of trends in food intake in

American children. Between 1994 and 2010,

when the rates of childhood and adolescent obe-

sity rose ~50%, the total energy intake of chil-

dren as assessed by dietary recall declined 10%,

and the relative intake of solid fats and added

sugars as a percent of total energy intake fell

from 39% to 33% [44–46]. The relative decline

1 Childhood Obesity in the Modern Age: Global Trends, Determinants, Complications, and Costs

10

in sugar intake (from 18% to 14%) was greater

than that of solid fat (21% to 19%, 44–46). The

largest decreases in energy intake were said to

have occurred in Mexican American children and

other low-income children from families with

less educated parents [45], that is, among groups

with some of the highest rates of childhood obe-

sity. Moreover, daily per capita food and bever-

age purchases (as assessed by market bar code

analysis) by households have by report declined

since 2001 in African American families, whose

rates of severe obesity are among the highest

recorded in the United States. Other investigators

[47] report that energy intake from fast-food res-

taurants also decreased for American children

between 2003 and 2010. Similar observations

were recorded in a cross-sectional study [48] in

Australia, where an increasing prevalence of

childhood obesity was accompanied by a reduc-

tion in consumption of sugar and sugar- sweetened

beverages.

A different impression is conveyed by analy-

ses [26, 49] of food balance sheets provided

by the United Nation’s Food and Agricultural

Organization (FAO). While these do not mea-

sure food consumption, they provide estimates

of a country’s food supply and the availabil-

ity of nutrients for human consumption when

adjusted for imports and exports and for food

fed to livestock or used for seed. Review of food

balance sheets [26] suggests that worldwide per

capita calorie availability (Fig. 1.7) increased

20% between 1961 and 2011, with marked

increases in vegetable oils (96%), eggs (71%),

fish (59%), meat (55%), and sugars and sweeten-

ers (41%). Modeling of FAO data (49) suggests

that increases in food energy supply are sufficient

to explain population weight gain, at least in the

developed world.

Daily per capita kcal availability in the

highest- income countries (3210) is estimated to

be 33% higher than that in the lowest-income

countries (2454). However, relative calorie avail-

ability has increased most dramatically between

1961 and 2011 in low-middle- and upper-middle-

income countries, owing to striking increases in

vegetable oils, eggs, meat, milk, and sweets. This

finding concords with the striking increases in

childhood obesity rates in developing countries

as people adopt a Westernized lifestyle and diet.

Dietary Patterns and the Development of Childhood Obesity

It is possible that the reported reductions in

caloric intake in the United States and other

developed countries during the past 16 years

represent a response to prior weight gain in cer-

tain segments of the population. Longitudinal

prospective studies of the relationship between

food intake and fat deposition are more useful

than cross-sectional analyses for identifying

determinants of childhood obesity. The best

prospective studies have employed an analysis

of dietary patterns [50, 51] in a large cohort of

6500 children enrolled in the ALSPAC study

(UK) at age 5–7 years and followed through age

15 years. Strengths of the study include the use

of 3-day food diaries before each clinic visit,

methodology to identify unreported energy

intake, and objective measurements of fat mass

by DEXA scan.

The authors identified two predominant

dietary patterns. The first (Fig. 1.8) comprised a

diet high in energy density, fats, and sugars

(cakes, chocolate, processed meats, sugary

drinks, whole milk, chips, oils, cheese) and low

in fiber, fruits, and vegetables. The second

3000

2500

Total Calories

Vegetal Products

Animal Products

2000

1500

kca

l /

da

y

1000

500

Year

1950

1960

1970

1980

1990

2000

2010

2020

0

Fig. 1.7 Changes in worldwide per capita calorie avail-

ability between 1961 and 2011. (Used with permission of

Elsevier from Dave D, Doytch N, Kelly IR. Nutrient

intake: A cross-national analysis of trends and economic

correlates. Soc Sci Med. 2016 Jun;158:158–67)

M. Freemark

11

(Fig. 1.9) was high in free sugars but low in fat

content, energy density, whole milk, oils, cheese,

chips, and eggs. The diet high in energy, fat, and

sugar and low in fiber, fruits, and vegetables at

age 5–7 year was associated with higher percent

body fat and excess adiposity in childhood and

adolescence (Fig. 1.10, top). In contrast, the diet

high in free sugars but low in fat and energy den-

sity did not predict subsequent percent body fat

or excess adiposity (Fig. 1.10, bottom). A dietary

pattern consisting of high-fat, high-energy foods

without excess sugar was not identified in this

cohort. Nevertheless, these findings suggest that

it is the combination of excess fat and sugar,

rather than a unique or single macronutrient,

which predisposes to childhood obesity. This

might explain the increases in childhood obesity

in the developing world, where a dramatic rise in

childhood and adult obesity rates has been

accompanied by striking increases in access to

low-cost vegetable oils, animal products, and

simple sugars. A detailed analysis of dietary

Confectionery, chocolateCakes, biscuits

Sugary drinksLow fibre breads

CrispsLow fibre breakfast cereals

Processed meatsWhole milkDiet drinks

Margarine, oilsCheese

Ice creamButterHot drinksBreaded meat, fishSpreads

Cereal mixed dishBread, other

EggsPizzaPotato, fried

CondimentsMeat mixed dishes

Nuts, seedsLow calorie sauces

Fruit juicesSugar free confectionery

PuddingsVegetable mixed dish

Vegetables, friedSoups

FishMeat substitutes

Fruit, otherLow fat milk

Meat, poultryYoghurts

Refined grainsHigh calorie sauces

WaterLegumes

Factor loading

Potato, boiledHigh fibre breads

High fibre breakfast cerealVegetables, not fried

Fruit, fresh

-0.6 -0.4 -0.2 0 0.2 0.4 0.6

Fig. 1.8 A dietary pattern high in energy density, fats,

and sugars (cakes, chocolate, processed meats, sugary

drinks, whole milk, chips, oils, cheese) and low in fiber,

fruits, and vegetables. (From Ambrosini GL, Johns DJ,

Northstone K, Emmett PM, Jebb SA. Free Sugars and

Total Fat Are Important Characteristics of a Dietary

Pattern Associated with Adiposity across Childhood and

Adolescence. J Nutr. 2016; 146: 778–784)

1 Childhood Obesity in the Modern Age: Global Trends, Determinants, Complications, and Costs