Early disturbances in insulin secretion in the development of type 2 diabetes mellitus.

After a short description of normal glucose homeostasis, recent findings in relation to insulin release in three groups with a high risk of future development of type 2 diabetes are described. Hyperglycemic clamps in subjects with impaired glucose tolerance (IGT) clearly indicate that pancreatic beta cell function is decreased, in addition to the decreased insulin sensitivity. In women with former gestational diabetes mellitus (GDM), insulin release is also lower than in controls. In Caucasian first-degree relatives (FDRs) with normal glucose tolerance, various studies have shown that beta cell function is lower than in controls, while on the average insulin sensitivity is normal. This implies that beta cell function is disturbed earlier in subjects at risk of developing diabetes than is often appreciated. In the near future, the genetic studies currently underway will presumably unravel the pathogenesis of disturbances both in insulin secretion and in insulin action, in type 2 diabetes mellitus.