Bezafibrate-induced improvement in glucose uptake and endothelial function in protease inhibitor-associated insulin resistance

Abstract

Protease inhibitors used as therapy for HIV-1 infection have been associated with metabolic side-effects such as peripheral fat wasting, central adiposity, hyperlipidaemia and insulin resistance. This metabolic disorder is known as the lipodystrophy syndrome. This syndrome can be recognized by the early appearance of an increase in serum triglyceride, cholesterol and plasma-free fatty acid levels. Here, we describe an HIV-1 positive patient with the lipodystrophy syndrome in whom a decline in serum triglycerides was seen along with a significant improvement in glucose uptake following treatment with bezafibrate for 3 months. This improvement may be a consequence of the Randle effect, i.e. increased availability of plasma-free fatty acids is negatively correlated to glucose uptake. We also noted a significant improvement in endothelial-dependent flow-mediated dilatation after treatment with bezafibrate. This effect could result from the increased glucose uptake observed and a decrease in insulin resistance secondary to the lowered triglyceride levels by bezafibrate. We conclude that bezafibrate may be of clinical utility in the lipodystrophy syndrome, through its beneficial effects on insulin resistance, glucose uptake and endothelial dysfunction.