The pathophysiological basis for intensive insulin replacement.

Abstract

Both type I and type II diabetes are characterised by a progressive decrease in beta-cell function and mass. In type I diabetes, autoimmune destruction results in rapid loss of beta-cell function, and insulin therapy is essential to maintain normoglycaemia. In type II diabetes, a diminished or absent first-phase insulin release is the earliest metabolic defect, which is accompanied by lack of prandial suppression of hepatic glucose production, increased postprandial glucose excursions and late insulin hypersecretion. Furthermore, chronic exposure to elevated glucose, even to intermittent postprandial spikes, results in further deterioration of the beta-cell function ('glucotoxicity'). By the time type II diabetes is diagnosed, beta-cell function and mass have declined by about 50%. With the progression of the disease and glucotoxicity there is continuous decrease in beta-cell mass due to increased apoptosis that results in absolute insulin deficiency. By then, patients require insulin administration to maintain glucose control. An increasing body of evidence demonstrates the importance of preserving endogenous beta-cell function both in type I and type II diabetes. Early and intensive glycaemic control, using regimens which re-create a physiological insulin profile, controlling postprandial as well as fasting glucose levels, offers the most promise for preserving beta-cell function, decreasing disease progression, and reducing the chronic complications of diabetes.