Metabolic Syndrome (eBook)

Christopher Byrne trained as a physician and clinicalscientist at Cardiff, Cambridge and Stanford Universities. AfterMedical Research Council clinical science fellowships he wasappointed Professor of Endocrinology & Metabolism atSouthampton University Hospitals Trust, UK. He is an academicdiabetologist with clinical and molecular research interests in thepathogenesis of the metabolic syndrome, and the mechanisms linkingmetabolic syndrome with type 2 diabetes and cardiovascular disease.His publications span a range of disciplines from epidemiologicalto gene expression studies. Sarah Wild trained in medicine in London and Cambridgeand subsequently received training in epidemiology at StanfordUniversity and the London School of Hygiene and Tropical Medicine.She is currently senior lecturer in epidemiology at the Universityof Edinburgh. Her research interests include the global burden ofdiabetes and metabolic syndrome and cardiovascularepidemiology.

The Metabolic Syndrome 3
Contents 7
Foreword 13
Preface 15
List of Contributors 17
1. The Global Burden of the Metabolic Syndrome and its Consequences for Diabetes and Cardiovascular Disease 19
Introduction 19
Definition of the metabolic syndrome 20
Available data on prevalence of the metabolic syndrome 22
Factors that influence prevalence of the metabolic syndrome and variation between populations 29
Interpretation of data on prevalence of the metabolic syndrome 36
Summary of available data 37
Pathogenesis of the metabolic syndrome 37
Consequences of the metabolic syndrome 45
Conclusions 50
References 50
2. Ethnicity and the Metabolic Syndrome 61
Introduction 62
The metabolic syndrome and ethnicity 62
Epidemiology of ethnic differences in the risk for cardiovascular disease 75
Association between the metabolic syndrome, cardiovascular disease and ethnicity 80
Potential mechanisms for ethnic differences in the metabolic syndrome 83
Lessons and challenges of study of ethnicity in terms of disease risk 90
Clinical implications 93
Conclusions 93
References 94
3. Developmental Origins of Vascular Dysfunction and Disease 103
Introduction 103
Endothelial cell function 104
Endothelial dysfunction 106
Epidemiology 108
Experimental evidence 114
Opportunities for intervention and screening 121
Conclusions 125
References 126
4. Developmental Origins of Insulin Resistance and Type 2 Diabetes 141
Introduction 141
Thrifty phenotype hypothesis 143
Foetal insulin hypothesis 144
Human studies 145
Animal studies 147
Hormonal insults 147
Surgical intervention 148
Nutritional models of early growth restriction 148
Conclusions 154
References 154
5. Recent Progress in the Identification of Genes Predisposing to the Metabolic Syndrome 161
Introduction 162
The genes for many of the monogenic components of the metabolic syndrome are now known 162
Genetic component to common diseases of the metabolic syndrome: genes have proved difficult to find compared with monogenic diseases of the metabolic syndrome 163
Finding the genes that predispose to diseases of the metabolic syndrome: to improve understanding of the aetiology and treatment 164
Improved clinical resources, new technology and the human genome project: helping the quest to find genes influencing metabolic syndrome diseases 165
Genes known to alter the risk of metabolic syndrome diseases 166
Conclusion 173
References 174
6. Atherothrombosis and the Metabolic Syndrome 181
Introduction 181
The metabolic syndrome: interaction with coagulation and fibrinolysis 182
Insulin resistance and endothelial dysfunction 183
The haemostatic mechanism 184
The haemostatic mechanism and insulin resistance 186
Plasminogen activator inhibitor-1 186
Tissue plasminogen activator 188
Factor VII 188
von Willebrand factor and factor VIII 190
Fibrinogen 191
Factor XII 191
Factor XIII B-subunit 192
Platelets and the metabolic syndrome 193
Summary and conclusions 194
References 196
7. Oxidative Stress, Insulin Resistance and Cardiovascular Disease 207
Introduction 207
From overfeeding to insulin resistance: the role of oxidative stress 209
Oxidative stress as a common pathogenic factor for the dysfunction of beta and endothelial cells 211
From insulin resistance to impaired glucose tolerance: the role of oxidative stress 213
From impaired glucose tolerance to diabetes and endothelial dysfunction 214
The possible link between oxidative stress and inflammation in insulin resistance, diabetes and cardiovascular disease 215
Oxidative stress as the connection between nutrition overload and diabetes and related cardiovascular complications: therapeutic implications 216
References 218
8. Inflammation, Cardiovascular Disease and the Metabolic Syndrome 225
Introduction 226
Role of inflammation in atherosclerosis 227
Relation between inflammation and endothelial function in humans 230
Role of acute-phase response in atherosclerosis 231
Is C-reactive protein mechanistically linked to atherosclerosis? 231
Inflammatory markers as predictors of cardiovascular disease 233
Inflammation and insulin resistance 238
Inflammatory markers as predictors of the metabolic syndrome and its components 242
Lifestyle and drug interventions 245
References 248
9. Adipocytokines and the Pathogenesis of the Metabolic Syndrome 257
Introduction 257
Adipocytokines and the metabolic syndrome 259
Summary and perspective 269
References 270
10. Peripheral Arterial Disease 281
Introduction 281
Definition and pathogenesis of peripheral arterial disease 282
Clinical spectrum 282
Descriptive epidemiology 283
Relation of peripheral arterial disease to ischaemic heart disease and stroke 285
Risk factors for peripheral arterial disease in relation to the metabolic syndrome 285
The metabolic syndrome and peripheral arterial disease 290
Prognosis of peripheral arterial disease 290
Conclusion 291
References 292
11. Non-alcoholic Steatohepatitis 297
Introduction 298
Aetiology 299
Diagnosis 299
Pathogenesis 301
Treatment 308
References 313
12. Polycystic Ovary Syndrome 323
Introduction 324
Insulin resistance in polycystic ovary syndrome and its role in reproductive abnormalities 324
Insulin resistance and metabolic features in women with polycystic ovary syndrome 327
Mechanisms to lessen diabetes and vascular risk in women with polycystic ovary syndrome 338
Future research questions in relation to long-term diabetes and vascular risk in polycystic ovary syndrome 343
Conclusion 344
References 345
13. Nutrition: It’s Relevance in Development and Treatment of the Metabolic Syndrome 351
Introduction 352
Weight loss and energy balance 352
Dietary fat and insulin sensitivity 355
Dietary fibre and the glycaemic index 360
Dietary patterns 361
Conclusions 363
References 364
14. Growth Hormone, Exercise and Energy Expenditure in the Metabolic Syndrome 371
Introduction 371
Description of growth hormone/insulin-like growth factor axis 372
The growth hormone/insulin-like growth factor-I system and the metabolic syndrome 380
Exercise and the metabolic syndrome 385
Therapeutic potential of the growth hormone/insulin-like growth factor-I axis 389
Conclusion 391
References 392
15. Treatments for the Metabolic Syndrome 399
Introduction 400
Targets for treatment 402
Treatment by lifestyle modification 403
Medical treatment of the metabolic syndrome 407
Polypharmacy in the treatment of the metabolic syndrome 415
Conclusions 416
References 416
Index 425

"...an excellent resource for clinical researchers andepidemiologists..." (Clinical Chemistry, June 2007)

"This is a well written, current review of the epidemiology,pathogenesis, and consequences of the metabolic syndrome."(Doody's Health Services)

"'The Metabolic Syndrome' is an excellent collection of updatedreviews, and it provides a valuable background for understandingmany aspects of this fascinating cluster of risk factors...excellent collection of updated reviews ... provides avaluable background for understanding many aspects of thisfascinating cluster of risk factors." (New England Journalof Medicine, June 22, 2006)

"Byrne and Wild bring together leading researchers in the fieldto address the latest work ..." (SciTech Book News, December2005).