Management of Pediatric Obesity and Diabetes (eBook)

1: Genetics of Obesity 29
1.1 Introduction 29
1.2 Monozygotic and Dizygotic Twin Pair Studies 30
1.3 Genetic Loci Identified in Common Obesity 32
1.4 Obesogenic Genes from Association Studies of Common Obesity 32
1.5 Genes Protecting from Obesity 38
1.6 Single Gene Disorders Resulting in Human Obesity 39
1.7 Role of Genetic Counseling 39
1.8 Conclusion 40
References 40
2: Fetal Origins of Obesity and Diabetes 44
2.1 Introduction 44
2.2 Maternal Obesity 45
2.3 Effect of Maternal Obesity on the Offspring Early Weight Gain is Childhood Age and Sex Dependent 45
2.3.1 Maternal Obesity and Fetal Macrosomia 49
2.4 Maternal Obesity and Fetal Pancreatic Function and Insulin Resistance 50
2.5 Maternal obesity and Fetal Monocyte Activation: Possible Mechanism of Developmental Programming 50
2.6 Fetal Monocyte Activation in a Baboon Model of Maternal Obesity 50
2.7 Material and Methods 51
2.7.1 Animal Care and Maintenance 51
2.7.2 FACS Analyses 51
2.8 Results 52
2.8.1 Maternal Morphometry 52
2.8.2 Fetal Morphometry 53
2.8.3 Maternal and Fetal PBMC Transcriptome Analyses 53
2.8.4 Fetal Monocytes Angiogenic and Inflammatory Response in a Baboon Model of Maternal Obesity 53
2.9 Discussion 55
2.10 Other Factors During Fetal Development Contributing to Risks of Obesity and Disease 55
2.10.1 Genetics 55
2.11 Epigenetics 56
2.12 Conclusion 57
References 57
3: b-Cell Growth Mechanisms 68
3.1 Introduction 69
3.1.1 b.-Cell Mass Maintenance: A Dynamic Balance of Several Parameters 69
3.2 Measuring b-Cell Growth Parameters 70
3.2.1 b.-.Cell Mass 70
3.2.2 Proliferation 70
3.2.3 Neogenesis 71
3.2.4 b.-.Cell Size 72
3.2.5 b.-Cell Death and Clearance 72
3.3 b-Cell Mass Compensation 72
3.3.1 Impact of Proliferation vs. Neogenesis 73
3.3.2 Importance of Neogenesis During Development 74
3.3.3 Impact of Individual b-Cell Growth and Enhanced Survival 75
3.4 Regulation of b-Cell Growth: The Importance of the Insulin Signaling Pathway 76
3.4.1 The Key Players 76
3.4.2 Regulation of Proliferation 77
3.4.3 Regulation of Neogenesis 78
3.4.4 Cell Growth 80
3.4.5 Cell Survival 80
3.5 Further Fine-Tuning b-Cell Growth and Survival 81
3.5.1 The Role of Glucoincretins 81
3.5.2 Nutrient and Glucose Signaling Pathways Regulating b.-.Cell Growth 82
3.5.3 Neurally Derived Growth Factors 84
3.6 Concluding Remarks 85
References 86
4: Race/Ethnic and Socioeconomic Disparities in Body Mass Index (BMI) and the Resulting Spread of Obesity and “Adult-Onset” Dia 96
4.1 Introduction 96
4.1.1 The Escalating Obesity Problem in the United States 96
4.1.2 Obesity and T2DM Epidemics Among Children and Adolescents 97
4.2 Conceptual Framework: Sociodemographic and Behavioral Pathways to High BMI and T2DM 98
4.2.1 The Effects of Gender on Eating and Exercise Behavior and on BMI 99
4.2.2 The Impacts of Socioeconomic Status on Nutritional and Exercise Behavior 99
4.2.3 The Impacts of Race/Ethnicity on Behavior Through Socioeconomic Status 100
4.2.4 Social Influences in Economically Disadvantaged Neighborhoods 101
4.3 Research Questions and Hypotheses 101
4.4 Methods 102
4.4.1 Data 102
4.4.2 Measures 102
4.4.2.1 Outcome Variables 102
4.4.2.2 Background Variables 109
4.4.2.3 Mediating Variables 109
4.5 Statistics 109
4.6 Results 111
4.6.1 Distribution of the Variables 111
4.6.2 Relation of Socioeconomic Status with Eating and Exercise Behavior 112
4.6.3 Relation of Socioeconomic Status with BMI and T2DM 112
4.6.3.1 Low Income and High BMI 113
4.6.3.2 Low Income and T2DM 113
4.6.4 Relation of Race/Ethnicity with Socioeconomic Status, Behavior, BMI, and T2DM 113
4.6.4.1 Race/Ethnicity and Income 113
4.6.4.2 Race/Ethnicity and Eating Behaviors 114
4.6.4.3 Race/Ethnicity and Exercise Behaviors 114
4.6.4.4 Race/Ethnicity and BMI 115
4.6.4.5 Race/Ethnicity and T2DM 115
4.6.5 Other Findings 116
4.6.5.1 BMI and Gender 116
4.6.5.2 BMI and Eating variables 116
4.6.6 Regression Models of Demographic Factors, Health Behavior, and BMI 116
4.7 Discussion 119
References 122
5: Assessment and Treatment of Cardiovascular Disease in Obese Children 125
5.1 Introduction 125
5.1.1 Overview 125
5.1.2 Prediction of Adult Risk 127
5.1.3 Early Atherogenesis 127
5.2 The Metabolic Syndrome 129
5.2.1 Overview 129
5.2.2 Defining Cut Points 129
5.2.3 Clinical Use 133
5.3 Physical Measures of Cardiovascular Assessment 135
5.3.1 Overview 135
5.3.2 Physical Examination Measurements 136
5.3.2.1 Height, Weight, and Body Mass Index 136
5.3.2.2 Waist 136
5.3.2.3 Blood Pressure 136
5.3.3 Left Ventricular Mass 137
5.3.4 Arterial Wall Stiffness 138
5.3.5 Intima-Media Thickness 139
5.4 Biochemical Measurements of Cardiovascular Risk 140
5.4.1 Overview 140
5.4.2 Insulin Resistance 140
5.4.3 Obesity-Related Dyslipidemia 141
5.4.4 Apolipoproteins 142
5.4.4.1 ApoB:ApoA-I Ratio 144
5.4.4.2 ApoC-III 144
5.4.4.3 Lp(a) 145
5.4.4.4 ApoE 146
5.4.4.5 LpA-I and LpA-I:A-II 146
5.4.4.6 NMR Lipoprotein Profile 147
5.5 Adhesion Molecules and Inflammation 148
5.6 Intervention 149
5.6.1 Overview 149
5.6.2 Lifestyle 150
5.6.3 IMT Reversal by Exercise 150
5.6.4 Dyslipidemia Treatment 150
5.6.5 Hypertension Treatment 152
5.7 Conclusions 152
ReferenceS 154
6: Community-Based Approaches to Reduce Pediatric Obesity 165
6.1 USA-Based Programs 165
6.1.1 Seed to Table Program (Maplewood, Missouri) 165
6.1.2 America Scores Program (Saint Louis, Missouri) 168
6.1.3 Healthy Kids, Healthy Communities (Northern Mississippi) 168
6.1.4 Healthy Schools Initiative (South Carolina) 169
6.1.5 Healthy 100 Kids (Florida) 169
6.1.6 Follow Me! Healthy Parents, Healthy Kids (Columbus, Ohio) 170
6.1.7 CATCH Program (Texas) 170
6.1.8 Just For Kids! Obesity Workbook (San Francisco, California) 170
6.1.9 PE4life 171
6.1.10 All 4 Kids: Happy, Happy, Active, Fit program (Las Vegas, Nevada) 172
6.1.11 Way to Optimal Weight: WOW (Bangor, Maine) 172
6.1.12 On The Move (New Orleans, Louisiana) 172
6.1.13 Pediatric Fitness Clinic (University of Wisconsin School of Medicine) 172
6.1.14 Bienestar Health Program (San Antonio, Texas) 173
6.2 International Programs 173
6.2.1 England 173
6.2.2 Australia 173
6.2.3 France 174
6.2.4 China 175
References 175
7: Physical Activity Approaches to Pediatric Weight Management 177
7.1 Introduction 177
7.2 Physical Activity and Recommendations 178
7.3 Literature Search 179
7.4 Obesity Prevention Programs 180
7.4.1 School-Based Prevention Programs 180
7.4.2 Family-Based Prevention Programs 181
7.4.3 Community- and Clinic-Based Interventions to Prevent Obesity 195
7.4.4 Policy and Environmental-Based Prevention Interventions 195
7.5 Obesity Treatment Interventions 198
7.5.1 School-Based Treatments 198
7.5.2 Family-Based Treatments 198
7.5.3 Community-Based and Clinical Treatments 210
7.6 Conclusion and Future Challenges 215
References 218
8: Behavior Modification in Pediatric Obesity 224
8.1 Introduction 225
8.2 Behavioral Modification 225
8.2.1 Key Behavioral Modification Techniques 228
8.2.1.1 Goal Setting 228
8.2.1.2 Stimulus Control 232
8.2.1.3 Self-Monitoring 234
8.2.2 Behavior Modification and New Technologies 235
8.3 Challenges in Treating Child and Adolescent Obesity in Usual Clinical Practice 235
References 240
9: Surgical Approaches to Pediatric Obesity 243
9.1 Introduction 243
9.2 Patient Selection and Surgical Indications 244
9.2.1 General Criteria 244
9.2.2 Early Intervention 245
9.2.3 Age Limits 245
9.2.4 Predictors of Outcomes 246
9.3 Preoperative Assessment and Preparation 246
9.3.1 Clinical Evaluation 246
9.3.2 Surgical Assessment 246
9.3.3 Preoperative Work Up 246
9.3.4 Preoperative Counseling 247
9.3.5 Concurrent and Preoperative Medications 248
9.4 Anesthetic Considerations in the Obese 249
9.4.1 Anesthesia for Bariatric Surgery 249
9.4.2 Sleep Apnea 249
9.4.3 Intraoperative Considerations 250
9.4.3.1 Positioning 250
9.4.3.2 Monitoring 250
9.4.3.3 Induction, Intubation, and Maintenance of Anesthesia 250
9.4.3.4 Pharmacology/Weight-Based Dosing 251
9.4.3.5 Other Technical Issues 251
9.5 Types of Bariatric Surgery in Adolescents and Children 252
9.5.1 Current Procedures 252
9.5.2 Roux-en-Y Gastric Bypass 252
9.5.3 Laparoscopic Gastric Banding 253
9.5.4 Sleeve Gastrectomy 254
9.5.5 Choosing the Procedure 255
9.6 Physiology of Bariatric Surgery 255
9.6.1 Gastric Banding (LAGB) 255
9.6.2 Gastric Sleeve 256
9.6.3 Roux-en-Y Gastric Bypass (RYGB) 256
9.6.4 Aspects Common to All Bariatric Surgery Procedures 256
9.6.5 Eating Behavior Adaptation 257
9.7 Postoperative Management and Follow-Up Protocols 257
9.7.1 Postoperative Care on Priority 257
9.7.2 Follow-Up Protocol 257
9.7.3 Postoperative Diet 258
9.7.4 Physical Activity 258
9.7.5 Bathing 258
9.8 Complications and Outcomes 258
9.8.1 Complications of Laparoscopic Gastric Banding 258
9.8.2 Laparoscopic Sleeve Gastrectomy 262
9.8.3 Gastric Bypass 262
9.9 Effects of Surgery on Comorbid Conditions 262
9.9.1 Obstructive Sleep Apnea 262
9.9.2 Type 2 Diabetes Mellitus (T2DM) 263
9.9.3 Hyperlipidemia 263
9.9.4 Hypertension 263
9.9.5 Quality of Life 263
9.9.6 Hormonal Disturbance 264
9.9.7 Nonalcoholic Fatty Liver Disease 264
9.9.8 Long-Term Survival 264
9.10 Summary 264
references 266
10: Epidemiology of Type 2 Diabetes Mellitus in Pediatric Populations 272
References 282
11: Nutrition for the Diabetic Child 286
11.1 Introduction 286
11.2 General Dietary Goals with Prediabetes or Diabetes 287
11.2.1 Carbohydrates 287
11.2.2 Protein 288
11.2.3 Fats 289
11.3 American Diabetes Association Recommendations [6] 290
11.4 The Diabetes Prevention Program 290
11.5 The Calorie Balance 291
11.6 Managing Diabetes with the DASH Eating Plan 293
11.7 Summary 294
References 295
12: Pharmacologic Approaches to Type 2 Diabetes and Obesity in Children and Adolescents 296
12.1 Case 297
12.2 Introduction 297
12.2.1 Pharmacological Agents for T2DM 298
12.3 Insulin Secretagogues 299
12.3.1 Sulfonylureas (Glyburide, Glipizide, and Glimepiride) 299
12.3.2 Meglitinides (Repaglinide and Nateglinide) 300
12.4 Insulin Sensitizer 305
12.4.1 Biguanides (Metformin) 305
12.4.2 Thiazolidinediones (TZDs) 305
12.5 Agents that Modify Carbohydrate and Lipid Absorption 307
12.5.1 Alpha-Glucosidase Inhibitors (Acarbose and Miglitol) 307
12.5.2 Lipase Inhibitors (Orlistat®, Xenical®, Alli®) 307
12.6 Glucagon-Like Peptide-1 (GLP-1) Agonists 307
12.6.1 Incretin Mimetics 309
12.6.2 DPP-IV Inhibitors 310
12.6.3 Amylin Analogs 310
12.7 Exogenous Insulin 311
12.8 Leptin 312
12.9 Management of Complications of T2DM 313
12.10 Future Directions for Pharmacologic Management of Pediatric T2DM and Obesity 313
12.11 Current Practice Recommendation 315
12.11.1 Medication Treatment in Childhood Obesity (Table 12.9) 315
12.11.2 Sibutramine (Meridia®) 317
12.11.3 Orlistat (Xenical®, Alli®) 317
12.11.4 Current Recommendations 318
12.12 Insulin Resistance and Polycystic Ovarian Syndrome 319
12.13 Conclusion 319
References 322
13: Insulin Pump Management 332
13.1 Introduction 332
13.2 History 332
13.3 How a Pump Works 333
13.3.1 Parts, Components, and Models 333
13.3.2 Insulin Delivery 335
13.4 Advantages and Disadvantages 339
13.5 The Ideal Candidate for an Insulin Pump 343
13.6 Ongoing Management with Pump Therapy 344
13.7 Future Advancements 345
13.8 Conclusion 346
References 346
14: Hyperglycemic Crisesin Diabetes Mellitus: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State 348
14.1 Introduction 348
14.2 Pathogenesis 350
14.2.1 Diabetic Ketoacidosis 350
14.2.2 Hyperglycemic Hyperosmolar State 352
14.2.3 DKA in Type 2 Diabetes 352
14.3 Precipitating Factors 352
14.4 Diagnosis 354
14.4.1 History and Physical Examination 354
14.4.2 Laboratory Evaluation 354
14.5 Differential Diagnosis 355
14.6 Treatment 356
14.6.1 Fluids 356
14.6.2 Insulin Therapy 361
14.6.3 The Two Bag System 363
14.6.4 Potassium 364
14.6.5 Bicarbonate 364
14.6.6 Phosphate 364
14.7 Immediate Posthyperglycemic Crisis Follow-Up Care 365
14.8 Complications of Therapy 366
14.9 Prevention 366
References 367
15: Monogenic Diabetes 370
15.1 Introduction 370
15.1.1 Typical Case Presentation of Monogenic Diabetes 375
15.2 MODY1 (HNF4a) 376
15.2.1 Genetics of MODY1 376
15.2.2 Clinical Features of MODY1 376
15.2.3 Complications of MODY1 376
15.2.4 Diagnosis of MODY1 376
15.3 MODY2 (GCK) 377
15.3.1 Genetics of MODY2 377
15.3.2 Clinical Features of MODY2 377
15.3.3 Who Should Be Tested? 378
15.4 MODY3 378
15.4.1 Genetics of MODY3 378
15.4.2 Clinical Features of MODY3 379
15.4.3 Complications of MODY3 379
15.4.4 Diagnosis of MODY3 379
15.5 Less Common MODY Forms 379
15.5.1 MODY4 379
15.5.2 MODY5 380
15.5.3 MODY6 380
15.6 Making the Diagnosis 380
15.7 Testing for MODY 380
15.7.1 Genetic Testing 381
15.7.2 Future of Diagnostic Technology for MODY 382
15.8 Treating Monogenic Diabetes 382
15.8.1 Treating MODY1 382
15.8.2 Treating MODY2 382
15.8.3 Treating MODY5 382
15.9 Detecting MODY in Elderly Populations 383
References 383
16: Secondary Causes of Obesity in Childhood 387
16.1 Introduction 387
16.2 Genetic Syndromes Associated with Obesity 389
16.3 Pleiotropic Syndromes 390
16.3.1 Prader–Willi Syndrome 390
16.3.2 Laurence–Moon–Biedl Syndrome 392
16.3.3 Alström Syndrome 393
16.3.4 Cohen Syndrome 395
16.3.5 Carpenter Syndrome 396
16.3.6 Klinefelter Syndrome 397
16.3.7 Turner Syndrome 398
16.4 Leptin Signaling Disruptions 399
16.4.1 Leptin Deficiency 399
16.4.2 Melanocortin-4 Receptor Deficiency 400
16.5 Endocrine Disorders Associated with Obesity 401
16.5.1 Endocrinopathies 401
16.5.2 Insulinoma 402
16.5.3 Diabetes Mellitus 402
16.5.4 Mauriac Syndrome 403
16.5.5 Pseudohypoparathyroidism 404
16.5.6 Growth Hormone Deficiency 406
16.5.7 Cushing’s Syndrome 407
16.5.8 Hypothyroidism 408
16.6 Hypothalamic Obesity 409
16.6.1 The Hypothalamus and Body Weight Regulation 410
16.7 Craniopharyngioma 412
16.7.1 Epidemiology and Pathology 412
16.7.2 Clinical Manifestations 412
16.7.3 Treatment Approaches 412
16.7.4 Treatment Outcomes and Obesity 413
16.7.4.1 Postsurgical Craniopharyngioma 413
16.7.4.2 Dextroamphetamine 415
16.7.4.3 Bariatric Surgery 415
16.8 Iatrogenic Causes of Obesity 416
16.8.1 Medications 416
References 417