Insulin Resistance: A Clinical Handbook

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1.1 Introduction.

1.2 Normal physiology.

1.2.1 Hormonal regulation of metabolism.

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1.2.2 The insulin receptor.

1.2.3 Post-binding events.

1.2.4 Glucose metabolism.

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1.2.5 Lipid metabolism.

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1.2.6. Protein metabolism.

1.2.7. Ion transport.

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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.

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1.6.1 Genetic causes of insulin resistance.

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1.6.2 Acquired causes of insulin resistance.

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1.6.3.Fetal origins hypothesis.

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Further Reading.

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Section 2. Insulin resistance in clinical medicine.

2.1 Clinical features.

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2.2 Factors influencing insulin sensitivity.

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2.2.1 Normal variation in insulin action.

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2.2.2 Sex.

2.2.3 Age.

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2.2.4 Physical activity.

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2.2.5 Tobacco.

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2.2.6 Alcohol.

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2.3. Physiological states of insulin resistance.

2.3.1 Puberty.

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2.3.2 Pregnancy.

2.3.4 The menopause.

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2.4 Severe insulin resistance syndromes.

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2.5 Insulin resistance and cardiovascular risk.

2.5.1 Syndrome X.

2.5.2 Obesity.

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2.5.3 Regional adiposity.

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2.5.4 Impaired glucose tolerance.

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2.5.5 Type 2 diabetes.

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2.5.6 Essential hypertension.

2.5.7 Dyslipidaemia.

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2.5.8 Endothelial dysfunction.

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2.5.9 Microalbuminuria.

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2.5.10. Hyperuricaemia.

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2.5.11 Impaired Fibrinolysis.

2.5.12 Polycystic ovary syndrome.

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2.5.13 Non-alcoholic steatohepatitis.

2.6 Other disorders associated with insulin resistance.

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2.6.1 Counter-regulatory hormone secretion.

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2.6.2 Endocrinopathies.

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2.6.3 Chronic renal failure.

2.6.4 Cirrhosis.

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2.6.5 Cardiac failure.

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2.7 Miscellaneous inherited disorders.

2.8 Drug-induced insulin resistance.

Further Reading.

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Section 3. Management of insulin resistance and associated conditions.

3.1 Non-pharmacological measures.

3.1.1 Medical nutrition therapy.

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3.1.3 Alcohol.

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3.1.4 Tobacco.

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3.2 Drugs for type 2 diabetes.

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3.2.1 Biguanides.

3.2.2 Thiazolidinediones.

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3.2.3 Sulphonyulreas.

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3.2.4 Repaglinide.

3.2.5 a-glucosidase inhibitors.

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3.2.6 Insulin therapy.

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3.3 Anti-obesity drugs.

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3.4 Lipid-modifying drugs.

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3.5 Anti-hypertensive drugs.

3.6 Experimental therapies