michael s. freemark editor pediatric obesity
TRANSCRIPT
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: [email protected]
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