Insulin resistance in pathogenesis of type 2 diabetes mellitus

This review focuses on the mechanisms of impaired sensitivity to insulin associated with evolution of carbohydrate metabolism disorders from enhanced fasting glycemia (EFG) to impaired glucose tolerance (IGT) and type 2 diabetes. Disturbances of glucose utilization at the receptor and post-receptor levels are considered along with the role of glucose and lipotoxicity. Original data on insulin resistance (IR) in patients with disorders of carbohydrate metabolism are presented. Insulin sensitivity in DM2, EFG and IGT is shown to be 50, 25 and 15% lower respectively than in normal subjects. M-index positively correlates with BMI and quality of metabolic control (HbA(1c) and triglyceride levels). The differences in clinical and biochemical characteristics of DM2 patients are analysed depending on the degree of IR. Adiponectin and resistin levels in DM2 are shown to be lower than in healthy subjects while TNF-a and proinsulin levels increase. Therapy with metformin, pyoglitazone, and insulin improves insulin sensitivity even in patients with early disturbances of carbohydrate metabolism. It is concluded that intensive hypoglycemic therapy should be initiated before marked deterioration of insulin sensitivity developed.