Pediatric Obesity (eBook)

Preface 5
Contents 6
Contributors 9
Part I The Obesity Epidemic: A Global Perspective 12
1 Global Dynamics in Childhood Obesity: Reflections on a Life of Work in the Field 13
Introduction 13
Global Patterns and Trends 13
Comparative Levels of Childhood Obesity 14
Rich vs. Poor Sectors of Society 15
Why the Broad Shift in Energy Balance 15
The Sweetening of Child Diets 15
Large Increases in Edible Oil 16
Increased Intake of Animal Source Foods (Dairy, Beef, Pork, Poultry, Fish, and Eggs) 16
Marked Shifts in Patterns of Eating 17
Concurrent Shifts in Physical Activity 18
Underlying Changes 18
Brief Summary 19
References 19
Part II The Neuroendocrine Perspective: The Control of Appetite and Energy Expenditure 22
2 The Neuroendocrine Control of Energy Balance 23
Introduction 23
Components of the Afferent System 25
Alimentary Afferents That Promote Hunger 25
Alimentary Afferents That Promote Satiety 25
Metabolic Afferents Controlling Energy Balance 27
Central Processing 28
Anorexigenesis, POMC/ -MSH, and CART 28
Orexigenesis, NPY, and AgRP 28
Other Neuroendocrine Modulators of Energy Balance 29
Melanocortin Receptors (MCR) and Central Neural Integration 30
The Efferent System 30
The Sympathetic Nervous System (SNS) and Energy Expenditure 30
The Efferent Vagus and Energy Storage 30
The Hedonic Pathway of Food Reward 31
The Amygdala and the Stress Pathway of Food Intake 32
Negative Feedback of Energy Balance The Response to Caloric Deprivation 32
Leptin Resistance 33
Summary 34
References 34
Part III The Genetics of Childhood Obesity 41
3 Monogenic Obesity 42
Introduction 42
Monogenic Obesity Caused by Mutations in the Leptin/Melanocortin Pathway 43
1-Leptin and Leptin Receptor Deficiency 43
2-Proopiomelanocortin (POMC) Deficiency 45
3-Proprotein Convertase 1 Deficiency 45
4-Melanocortin 4 Receptor Deficiency 46
II-Monogenic Obesity with Neurological Features 46
1-Brain-Derived Neurotrophic Factor and Its Receptor TrkB 46
2-Single-Minded 1 Transcription Factor 47
III-A Continuum Between Monogenic and Polygenic Obesity 47
Conclusions and Perspectives 48
References 49
4 Syndromic Obesity 53
Overview 53
PraderWilli Syndrome (PWS) 53
Albright Hereditary Osteodystrophy 60
BardetBiedel Syndrome (BBS) 61
Alstrom Syndrome (AS) 62
SIM1 Deletion Syndrome 63
BDNF and Tropomyosin-Related Kinase B 64
Conclusions 65
Acknowledgments 65
Editor's Comment 65
References 65
5 Polygenic Obesity 71
Introduction 71
Polygenes for Body Weight 72
Candidate Gene Analysis and Genome-Wide Approaches 72
Melanocortin-4 Receptor Gene (MC4R) 73
Insulin-Induced Gene 2 (INSIG2) 74
Fat Mass and Obesity-Associated Gene (FTO) 74
More Polygenes Identified in Recent Genome-Wide Association Studies 75
Conclusions and Perspectives 76
Acknowledgments 77
Editor's Questions and Authors' Response 77
References 78
6 Racial Differences in Childhood Obesity: Pathogenesis and Complications 80
Introduction 80
Obesity and Race 81
Race and Genetic/Biological Differential in Risk of Obesity 81
Race, Obesity, and Genetics 81
Race, Obesity, and Biology 82
Hyperinsulinemia/Insulin Resistance 82
Lipid Metabolism 84
Race, Obesity, and Body Fat Distribution 85
Race and Environmental/Sociocultural Differential in Risk of Obesity 86
Obesity and Socioeconomic Status (SES) 86
Obesity and Sociocultural Differences 86
Race and Co-morbidities of Obesity 87
Race and Nonalcoholic Fatty Liver Disease 87
Race and Lipids 87
Race and Cardiovascular Disease 87
Race and Prediabetes and Type 2 Diabetes (T2DM) 88
Race and the Metabolic Syndrome 88
Race and the Treatment of Obesity 90
Closing Remarks and Future Directions 90
Acknowledgments 91
Editor's Questions and Authors' Response 91
References 91
Part IV Pre and Perinatal Determinants of Childhood Obesity 95
7 Maternal Determinants of Childhood Obesity: Weight Gain, Smoking, and Breastfeeding 96
Introduction 96
Maternal Weight Status 97
Pregravid Weight Status 97
Gestational Weight Gain 98
New Guidelines for Pregnancy Weight Gain in Overweight and Obese Women 98
Effects of Maternal Undernutrition 99
Postnatal Maternal Weight Status 99
Smoking 99
Breastfeeding 100
Maternal Dietary Habits and Physical Activity 101
Other Influences 102
Summary 103
Editor's Question and Authors' Response 103
References 103
8 Intrauterine Growth Retardation 106
Introduction 106
The Barker Hypothesis 107
The Developmental Origins of Health and Disease Hypothesis 107
Antenatal Pathogenesis Animal Models 108
Antenatal Pathogenesis Human Studies 109
Early Postnatal Pathogenesis Animal Models 110
Early Postnatal Pathogenesis Human Studies 111
Future Strategies Healthy Catch-Up Growth 112
Editor's Questions and Author's Response 112
References 113
9 Gestational Diabetes 116
Introduction 116
Fetal Programming: A Conceptual Framework 117
Consequences of Exposure to Diabetes During Pregnancy 117
Does Maternal Diabetes Type Matter 119
Programming of Fetal Growth and Adiposity by Maternal Obesity 119
Genetic, Familial, or Specific Intrauterine Effects 120
Possible Mechanisms Responsible for the Intrauterine Effects 121
Clinical and Public Health Implications 122
References 122
Part V The Roles of Diet and Energy Expenditure in Obesity Pathogenesis 126
10 The Role of Diet 127
Dietary Fat 129
Fibre Intake 129
Dietary Energy Density 129
Foods 130
Dietary Patterns 131
Eating Behaviour 133
Summary 134
Editor's Comment and Question and Authors' Response 134
References 135
11 Energy Expenditure in Children: The Role of NEAT 138
Introduction: Energy Expenditure 138
Measurement of Energy Expenditure and NEAT 140
Basal Metabolic Rate and Resting Energy Expenditure 140
Thermic Effect of Food 140
Energy Expenditure of Physical Activities 140
Defining Exercise and NEAT 141
NEAT Energy Expenditure 141
NEAT Variability 142
NEAT in Weight Gain and Obesity 142
NEAT Children 144
NEAT School 145
The Individual 145
Examples of NEAT Solutions 145
The Classroom 146
Examples of NEAT Solutions 146
The School 147
Possible NEAT Solutions 147
The Out-of-School Environment 149
Possible NEAT Solutions 149
Conclusion 149
Acknowledgments 150
Editor's Comments and Question and Authors' Response 150
References 151
Part VI Metabolic Complications of Childhood Obesity 153
12 Childhood Obesity and the Regulation of Growth, Thyroid Function, Sexual Development, and Calcium Homeostasis 154
Metabolic and Hormonal Disorders Causing Excess Fat Deposition 154
Effects of Obesity on Linear Growth and Bone Maturation 156
Thyroid Function 157
Gonadal Function and Pubertal Development 158
Glucocorticoid Production and Turnover 159
Calcium Homeostasis, Bone Mineralization, and Fractures 159
References 160
13 Pathogenesis of Insulin Resistance and Glucose Intolerance in Childhood Obesity 162
Pathophysiology of Insulin Resistance 163
Epidemiology of Altered Glucose Metabolism in Childhood 165
Pathophysiology of Altered Glucose Metabolism in Childhood 166
Dynamics of Pre-diabetic Conditions 167
Insulin Resistance (Metabolic) Syndrome in Childhood 168
Summary 169
Editor's Questions and Authors' Response 169
Editor's Comments 170
References 171
14 Pathogenesis and Management of Dyslipidemia in Obese Children 174
Introduction and Summary 174
Pathophysiologic Aspects 175
Basic Lipid Metabolism 175
Clinical Aspects 177
Assessment and Interpretation 177
Intervention 184
Summary 192
Editor's Comments 192
References 193
15 Fatty Liver Disease 199
Introduction 199
Natural History 200
Epidemiology 200
Histological Findings 201
Steatosis 202
Ballooning 203
Inflammation 203
Fibrosis 203
Etiopathogenesis 204
Accumulation of Fat in the Liver 204
Role of Insulin Resistance 205
Impact of Oxidative Stress 205
Function of Inflammatory Cytokines and Adipokines 206
Diagnostic Approaches 207
Serum Markers 207
Imaging Techniques 208
Liver Biopsy 208
Grading and Staging of NAFLD 208
Treatment of Fatty Liver Disease 210
Lifestyle Changes 210
Bariatric Surgery 211
Cytoprotective and Antioxidants Agents 211
Insulin Sensitizers 212
Lipid-Lowering Drugs 212
New Perspectives 213
Editor's Questions and Authors' Response 213
References 213
16 Pathogenesis of Hypertension and Renal Disease in Obesity 221
Introduction 221
Hypertension 221
Epidemiology 221
Blood Pressure Homeostasis 223
Pathophysiologic Mechanisms 223
Sympathetic Nervous System Activity 223
Renin--Angiotensin--Aldosterone System (RAAS) 225
Hyperinsulinemia/Insulin Resistance 225
Obstructive Sleep Apnea (OSA) 226
Adipose Tissue-Related Metabolic Factors 226
Renal Disease 228
Clinical Spectrum of Obesity-Related Glomerulopathy (ORG) 228
Renal Hemodynamics 228
Tubuloglomerular Feedback 229
Proteinuria 229
Renal Morphology 230
Pathophysiologic Mechanisms 231
Renin--Angiotensin--Aldosterone System (RAAS) 231
Metabolic/Adipocyte Factors 231
Summary 233
Editor's Questions and Authors' Response 233
References 234
17 Sleep-Disordered Breathing and Sleep Duration in Childhood Obesity 238
General Introduction 238
Sleep-Disordered Breathing and Obesity in Children 239
Introduction 239
Obesity as a Risk Factor of Sleep-Disordered Breathing in Children 240
Pathogenesis of Sleep Apnea in Obesity 241
Complications of Sleep-Disordered Breathing 242
Treatment of Sleep-Disordered Breathing in Obese Children and Adolescents 242
Conclusions for Daily Practice 244
Sleep Duration and Childhood Obesity 245
Introduction 245
Epidemiological Evidence 245
Mechanisms Linking Short Sleep Duration to Obesity 245
Conclusions for Daily Practice 246
Editor's Comments 246
References 247
18 The Long-Term Metabolic Complications of Childhood Obesity 250
Introduction 250
Obesity and Insulin Resistance (IR) as Chicken and Egg 251
Tracking of Obesity and IR from Childhood into Adulthood 251
Black--White Differences in Plasma Insulin and Obesity and Progression Over Time 252
Long-Term Risks of Childhood Obesity and Insulin Resistance (IR): Impaired Fasting Glucose, Impaired Glucose Tolerance, and T2DM 253
Childhood Obesity, Insulin Resistance (IR), and the Metabolic Syndrome 254
Childhood Metabolic Syndrome and Adult T2DM and CVD 255
Polycystic Ovary Syndrome 256
Intervention with Diet, Exercise, and Metformin in Obese, Hyperinsulinemic Children Reduces Metabolic Complications of Childhood Obesity 256
Conclusions 257
Editor's Question and Authors' Response 257
References 258
19 Childhood Obesity, Atherogenesis, and Adult Cardiovascular Disease 261
Pediatric Obesity and Atherosclerosis 261
Atherosclerosis and Cardiovascular Disease 261
Risk Factors and Atherosclerosis in Youth: Autopsy Studies 263
Risk Factors and Atherosclerosis in Youth: Cohort Studies 266
Endothelial Dysfunction and Atherosclerosis 266
Prevention of Adult Coronary Heart Disease 267
Conclusions 268
Editor's Questions and Authors' Response 269
References 271
Part VII Treatment of Childhood Obesity: Lifestyle Intervention 275
20 Family-Based Behavioral Interventions 276
Importance of Early Intervention 276
Family-Based Behavioral Interventions 277
Key Treatment Components of Family-Based Behavioral Interventions 279
Dietary Modification 280
Energy Expenditure Modification 281
Behavior Change Techniques 281
Family Involvement and Support 282
Problem of Weight Regain 285
Family-Based Weight Loss Maintenance Treatment 285
Expanding the Scope of Maintenance Treatment: A Multi-Level Approach 286
Components of a Family-Based, Multi-Level Maintenance Intervention 287
Conclusions and Future Directions 289
Acknowledgments 289
Editor's Comments 290
References 292
21 Exercise and Childhood Obesity 297
Introduction 297
What Do Young Children Know About Nutrition and Exercise and How Does This Affect Their Preferences 297
Obesity and Habitual Physical Activity 299
Obesity and Fitness 300
Hormonal Effects of Exercise in Obese Children 301
Obesity and Exercise-Related Food Choices 302
Exercise Training and Treatment of Childhood Obesity 303
References 306
22 School- and Community-Based Interventions 308
Introduction 308
Summary of the Literature 309
Summary of Articles of School--Community Programs for Obesity Prevention 309
General Description of the Intervention Trials 309
Target Populations 319
Theoretical and Participatory Approaches 319
Intervention Components Inside and Outside Schools 319
Process Evaluation 321
Psychosocial Measures and Behavioral Impacts 321
Health Outcomes 321
Community Measures 322
Study Results 322
Impact on Psychosocial Factors and Behavior 322
Impact on BMI and Anthropometric Measures 322
Impact on Community 322
Discussion 323
References 325
Part VIII Management of Obesity with Complications: Pharmacotherapy and Bariatric Surgery 329
23 Pharmacotherapy of Childhood Obesity and Pre-diabetes 330
Background 330
The Rationale for Pharmacotherapy 331
The Limits of Lifestyle Intervention 331
What Happens if Lifestyle Intervention Fails and Obesity Persists or Worsens Over Time? 331
Effects of Pharmacologic Agents in Obese Subjects 332
Sibutramine 333
Orlistat 335
Metformin 336
New Developments in Obesity Pharmacology: Incretin Mimetics and Selective Serotonin Receptor Agonists 339
Other Drugs/Hormones That Have Been Used to Treat Obesity 340
Summary of the Benefits and Risks of Pharmacologic Agents 340
Can We Identify Pediatric Candidates for Pharmacological Therapy 341
When Should We Intervene 341
Which Medication Should Be Used 342
How Long Do We Need to Treat 343
References 343
24 Pathogenesis and Management of Adiposity and Insulin Resistance in PCOS: Prevention and Treatment of the Metabolic Disease Components 347
Introduction: Polycystic Ovary Syndrome (PCOS) 347
Developmental Origin of PCOS and Its Evolution During Childhood 348
Genes and PCOS 349
Metabolic Dysfunction in PCOS 349
Mechanism of Insulin Resistance in PCOS 350
Adiposity in PCOS 351
Metabolic Syndrome in Adolescents with PCOS 352
Diagnostic Investigation 352
Management of Adolescents with PCOS 352
Summary 354
Editor's Questions and Authors' Response 354
Editor's Comment 354
References 355
25 Obesity and Metabolic Dysfunction in the Child with a Major Behavioral Disorder: Atypical Antipsychotics 358
Introduction 358
Effects of Psychotropic Medications and Other Drugs on Body Weight and Metabolic Function 359
Management of Excess Weight Gain in Patients Treated with Atypical Antipsychotics 360
Nonpharmacologic Interventions 360
Pharmacologic Interventions 361
Conclusion 362
References 363
26 Hypothalamic Obesity 366
Introduction 366
Incidence and Risk Factors 366
Pathogenesis 368
Sympathetic Nervous System Hypofunction 369
Vagal Hyperfunction 369
Presentation 370
Diagnosis 371
Treatment 371
Pharmacotherapy 372
Surgery 373
Summary 373
Acknowledgments 373
Editor's Questions and Author's Response 373
References 374
27 Bariatric Surgery in Adolescents 378
Introduction 378
Patient/Procedure Selection 379
Surgical Approaches 379
Pre-operative Considerations 383
The Operative Team 383
Pre-op Assessment 383
Questions Regarding Patient Age and Informed Consent 384
Outcomes, Complications, and Post-operative Considerations 384
BMI and Co-morbidities 384
Mechanisms of Weight Loss 385
Complications 385
Follow-Up 386
Summary 386
Editor's Questions and Authors' Response 386
Editor's Comments 388
References 389
Part IX Challenges to LongTerm Success 392
28 Neuroendocrine and Metabolic Adaptations in the Central Nervous System That Facilitate Weight Regain 393
Introduction 393
LeptinBrain Interactions During Fasting/Caloric Restriction 394
Leptin Signaling 394
Effects of Leptin on Appetite, Energy Homeostasis, and Behavior 395
CNS Targets for Leptin-Regulated Neurons in the Arcuate Nucleus 395
a. Hypothalamic Paraventricular Nucleus 395
b. Hypothalamic Dorsomedial Nucleus 396
c. Ventromedial Nucleus 396
d. Lateral Hypothalamus 397
Effects of Leptin on Thyroid Hormone Regulation 397
InsulinBrain Interactions During Fasting/Caloric Restriction 398
AdiponectinBrain Interactions During Fasting/Caloric Restriction 399
GhrelinBrain Interactions During Fasting/Caloric Restriction 399
EndocannabinoidBrain Interactions 400
Role of Nutrient Sensing During Fasting/Caloric Restriction 401
Integration: The Neuroendocrine Response to Caloric Deprivation and Weight Loss 402
References 19
29 The Socio-cultural Context for Obesity Prevention and Treatment in Children and Adolescents: Influences of Ethnicity and Gender 410
Introduction 410
Background 411
Physical Environments 413
Neighborhood and Community Environments 413
School Environments 413
Home Environments 414
Technology, Media, and Advertising Environments 414
Socio-cultural Variation 415
Infant Feeding 415
Caregiver, Family, and Peer Influences 415
Food Intake and Physical Activity 416
Body Image and Weight Concern 417
Addressing Socio-cultural and Contextual Influences in Interventions 417
Conclusion 419
References 419
Part X The Future of Childhood Obesity in the Global Marketplace 424
30 The Marketing and Distribution of Fast Food 425
Introduction 425
The Rise of Fast Food in the United States 427
International Expansion of Fast Food 429
The Power of Marketing 431
Fast-Food Companies on the Defensive 432
Conclusion 434
Acknowledgments 434
Editor's Question and Authors' Response 434
References 435
31 Local and National Policy-Based Interventions: To Improve Childrens Nutrition 437
Why Change Food Policies 438
Strengthening Federal Feeding Programs 438
Women, Infants, and Children Program 439
Child and Adult Care Feeding Program 439
National School Breakfast and Lunch Programs 440
Policy Interventions Designed to Change Food Industry Actions 442
Conclusions 443
Editor's Comment 444
References 444
Appendix 447
Subject Index 450