Free fatty Acids Becomes A New Target For Therapy

Elevated plasma FFA levels have been shown to account for up to 50% of insulin resistance in obese patients with T2DM. Obesity and type 2 diabetes mellitus (T2DM) are increasing at an accelerating rate in the US and other industrialized countries. Free fatty acids (FFA) have emerged as a major link between obesity and insulin resistance/T2DM. Normalization of FFA should therefore be considered a therapeutic target in obese, insulin-resistant individuals who have elevated plasma FFA levels.

Recent findings have shown that acute and chronic elevations of plasma FFA levels produce insulin resistance in many target tissues including skeletal muscle, liver, and vascular endothelial cells. In pancreatic [beta]-cells of normal subjects, FFA potentiate glucose-stimulated insulin secretion. This prevents development of T2DM in most obese, insulin-resistant individuals. In contrast, in prediabetic patients (including patients with first-degree relatives with T2DM or patients with impaired glucose tolerance) FFA is unable to stimulate glucose-mediated insulin secretion sufficiently to compensate for the insulin resistance. T2DM develops as result of the uncompensated insulin resistance.

In summary: Elevated plasma FFA levels have been shown to account for up to 50% of insulin resistance in obese patients with T2DM. Lowering of FFA in these patients, therefore, could be a new and promising approach to manage T2DM.

Current Opinion in Endocrinology & Diabetes. 11(5):258-263, October 2004.

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