Insulin Resistance (eBook)

Andrew J. Krentz, Lead Consultant in Diabetes and Endocrinology Southampton University Hospitals NHS Trust Southampton UK.

Insulin Resistance A Clinical Handbook 1
Contents 7
Preface 10
About the author 11
Acknowledgements 12
1 Pathophysiology of insulin resistance 13
1.1 Introduction 13
1.2 Normal physiology 15
1.2.1 Hormonal regulation of metabolism 15
1.2.2 The insulin receptor 17
1.2.3 Post-binding events 20
1.2.4 Glucose metabolism 21
1.2.5 Lipid metabolism 25
1.2.6 Protein metabolism 26
1.2.7 Ion transport 27
1.3 The concept of insulin resistance 27
1.3.1 Early studies of insulin action 27
1.3.2 Radioimmunoassays for insulin 27
1.4 Definitions of insulin resistance 29
1.5 Assessment of insulin action in vivo 31
1.5.1 Fasting insulin concentration 31
1.5.2 Dynamic techniques-endogenous insulin 36
1.5.3 Dynamic techniques-exogenous insulin 37
1.5.4 Mathematical modelling techniques 39
1.5.5 Insulin suppression test 40
1.5.6 Hyperinsulinaemic euglycaemic clamp technique 41
1.5.7 Complementary techniques 43
1.6 Mechanisms of insulin resistance 46
1.6.1 Genetic defects 46
1.6.2 Acquired forms of insulin resistance 49
1.6.3 Fetal origins hypothesis 56
1.7 Further reading 59
2 Insulin resistance in clinical medicine 62
2.1 Clinical features 62
2.2 Factors influencing insulin sensitivity 64
2.2.1 Normal variation in insulin action 64
2.2.2 Sex 68
2.2.3 Age 68
2.2.4 Physical exercise 68
2.2.5 Tobacco 70
2.2.6 Alcohol 71
2.3 Physiological states of insulin resistance 71
2.3.1 Puberty 71
2.3.2 Pregnancy 72
2.3.3 Menstrual cycle 74
2.3.4 The menopause 74
2.4 Severe insulin-resistance syndromes 75
2.5 Insulin resistance and cardiovascular risk 79
2.5.1 Syndrome X 83
2.5.2 Obesity 85
2.5.3 Regional adiposity 90
2.5.4 Impaired glucose tolerance 93
2.5.5 Type 2 diabetes mellitus 95
2.5.6 Essential hypertension 102
2.5.7 Dyslipidaemia 106
2.5.8 Endothelial dysfunction 110
2.5.9 Microalbuminuria 110
2.5.10 Hyperuricaemia 112
2.5.11 Impaired fibrinolysis 113
2.5.12 Polycystic ovary syndrome 115
2.5.13 Non-alcoholic steatohepatitis 118
2.6 Other disorders associated with insulin resistance 119
2.6.1 Counter-regulatory hormone secretion 119
2.6.2 Endocrinopathies 121
2.6.3 Chronic renal failure 122
2.6.4 Hepatic cirrhosis 123
2.6.5 Cardiac failure 123
2.7 Miscellaneous inherited disorders 123
2.8 Drug-induced insulin resistance 125
2.9 Further reading 126
3 Management of insulin resistance and associated conditions 131
3.1 Non-pharmacological measures 131
3.1.1 Medical nutrition therapy 131
3.1.2 Physical activity 136
3.1.3 Alcohol 140
3.1.4 Tobacco 142
3.2 Drugs for type 2 diabetes 143
3.2.1 Biguanides 144
3.2.2 Thiazolidinediones 152
3.2.3 Sulphonylureas 163
3.2.4 Meglitinide analogues 165
3.2.5 ?-Glucosidase inhibitors 167
3.2.6 Insulin 169
3.3 Antiobesity drugs 172
3.3.1 Sibutramine 172
3.3.2 Orlistat 173
3.3.3 Leptin 173
3.2.4 ?3-adrenocepter agonists 175
3.4 Lipid-modifying drugs 175
3.4.1 Fibric acid derivatives 175
3.4.2 Acipimox 176
3.4.3 Statins 177
3.4.4 Omega-3 fatty acids 178
3.5 Antihypertensive drugs 178
3.2.4 ?-adrenocepter agonists 179
3.5.2 Calcium-channel blockers 180
3.5.3 Angiotensin converting enzyme inhibitors 181
3.5.4 Angiotensin II receptor antagonists 182
3.5.5 ?1-Receptor blockers 182
3.5.6 Selective imidazoline receptor agonists 182
3.5.7 Aspirin 182
3.6 Experimental therapies 183
3.6.1 D-chzro-inositol 183
3.6.2 Non-thiazolidinedione PPAR-? agonists 184
3.6.3 ?-Lipoic acid 184
3.6.4 Insulin-like growth factor-1 185
3.6.5 Vanadium salts 185
3.6.6 The search for new drugs 186
3.7 Further reading 186
Index 191