Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus

Antiretroviral therapy (ART) is frequently associated with metabolic altera tions, including insulin resistance and diabetes mellitus. In this pilot st udy, we evaluated the effect of the PPAR gamma activator troglitazone on AR T-associated insulin resistance in HIV-infected patients with ART-associate d diabetes mellitus. Six patients with protease inhibitor (PI)-associated d iabetes mellitus, lipodystrophy and dyslipidemia were treated with troglita zone 400 mg q.d. for 3 months. Previous oral antidiabetics were discontinue d prior to the study. At baseline and after 3 months, insulin sensitivity ( intravenous insulin tolerance test), body composition (multifrequence bioel ectrical impedance analysis) and fat distribution (CT scan quantification) were assessed. Glycaemic control (fasting and postprandial blood glucose, f ructosamine, glycosylated haemoglobin) and serum lipid status were determin ed monthly. In four of the six patients, there was a clear improvement in i nsulin sensitivity, resulting in a reversal of insulin resistance in two of these patients. Overall, there was an increase in lean body mass and a dec rease in total body fat. The volume of visceral adipose tissue decreased wh ilst the volume of subcutaneous adipose tissue increased. Total cholesterol , LDL and HDL cholesterol increased, and total triglycerides and VLDL-chole sterol decreased. No adverse effects such as hepatotoxicity were observed. Treatment with troglitazone 400 mg q.d. can ameliorate and in some cases ev en reverse ART-associated insulin resistance. Therefore, further studies in cluding non-diabetic patients with ART-associated insulin resistance may be helpful in evaluating the long-term effects of thiazolidinediones on ART-a ssociated insulin resistance and other metabolic complications, such as adi pose maldistribution and dyslipidaemia.