Free fatty acids and type 2 diabetes mellitus.

Acute elevation of plasma free fatty acids (FFAs) is necessary for insulin secretion. Sustained elevation, however, leads to apoptosis of pancreatic beta-cells and is a major risk factor for cardiovascular disease and sudden death in patients with insulin resistance or a family history of diabetes mellitus, as well as in individuals with normal glucose tolerance. Data suggest that reduction of FFA plasma levels may reduce the incidence of cardiovascular disease in these at-risk patients. Thiazolidinediones have been shown not only to improve insulin sensitivity but also to reduce FFA plasma levels. Consequently, endothelial function is maintained, vascular smooth muscle cell proliferation and migration are minimized, elevated blood pressure and microalbuminuria are reduced, and high-density lipoprotein and low-density lipoprotein cholesterol particle sizes are improved.