Insulin resistance, defined as a reduced biological action of insulin, has emerged as a major factor in the development and progression of a number of common non-communicable diseases in man. The role of insulin resistance in the aetiology of type 2 diabetes is particularly well-established. However, insulin resistance has also come to be regarded as a key component of a broader syndrome of common metabolic defects that conspire to increase the risk of atherosclerotic coronary heart disease. The ramifications of insulin resistance now embrace many different medical specialties.

Section 1. Pathophysiology of insulin resistance 1.1 Introduction 1.2 Normal physiology 1.2.1 Hormonal regulation of metabolism 1.2.2 The insulin receptor 1.2.3 Post-binding events 1.2.4 Glucose metabolism 1.2.5 Lipid metabolism 1.2.6. Protein metabolism 1.2.7. Ion transport 1.3 The concept of insulin resistance 1.3.1 Early studies of insulin action 1.4 Definitions of insulin resistance 1.5 Assessment of insulin action in vivo 1.5.1 Fasting insulin concentration 1.5.2 Dynamic tests - endogenous insulin 1.5.3 Dynamic tests - exogenous insulin 1.5.4 Mathematical modelling techniques 1.5.5 The insulin suppression test 1.5.6 The hyperinsulinaemic euglycaemic clamp technique 1.6. Mechanisms of insulin resistance 1.6.1 Genetic causes of insulin resistance 1.6.2 Acquired causes of insulin resistance 1.6.3.Fetal origins hypothesis Further Reading Section 2. Insulin resistance in clinical medicine 2.1 Clinical features 2.2 Factors influencing insulin sensitivity 2.2.1 Normal variation in insulin action 2.2.2 Sex 2.2.3 Age 2.2.4 Physical activity 2.2.5 Tobacco 2.2.6 Alcohol 2.3. Physiological states of insulin resistance 2.3.1 Puberty 2.3.2 Pregnancy 2.3.4 The menopause 2.4 Severe insulin resistance syndromes 2.5 Insulin resistance and cardiovascular risk 2.5.1 Syndrome X 2.5.2 Obesity 2.5.3 Regional adiposity 2.5.4 Impaired glucose tolerance 2.5.5 Type 2 diabetes 2.5.6 Essential hypertension 2.5.7 Dyslipidaemia 2.5.8 Endothelial dysfunction 2.5.9 Microalbuminuria 2.5.10. Hyperuricaemia 2.5.11 Impaired Fibrinolysis 2.5.12 Polycystic ovary syndrome 2.5.13 Non-alcoholic steatohepatitis 2.6 Other disorders associated with insulin resistance 2.6.1 Counter-regulatory hormone secretion 2.6.2 Endocrinopathies 2.6.3 Chronic renal failure 2.6.4 Cirrhosis 2.6.5 Cardiac failure 2.7 Miscellaneous inherited disorders 2.8 Drug-induced insulin resistance Further Reading Section 3. Management of insulin resistance and associated conditions 3.1 Non-pharmacological measures 3.1.1 Medical nutrition therapy 3.1.3 Alcohol 3.1.4 Tobacco 3.2 Drugs for type 2 diabetes 3.2.1 Biguanides 3.2.2 Thiazolidinediones 3.2.3 Sulphonyulreas 3.2.4 Repaglinide 3.2.5 a-glucosidase inhibitors 3.2.6 Insulin therapy 3.3 Anti-obesity drugs 3.4 Lipid-modifying drugs 3.5 Anti-hypertensive drugs 3.6 Experimental therapies