The Effect of Rosiglitazone on Insulin Sensitivity, Beta Cell Function, Bone Mineral Density, and Body Composition in HIV-positive Patients on Highly-active Antiretroviral Therapy (HAART)

Highly active antiretroviral therapy (HAART) leads to lipodystrophy and is associated with detrimental changes in glucose and lipid metabolism. This study investigated the impact of rosiglitazone on insulin sensitivity, beta cell function, bone mineral density, and body composition in HIV+ nondiabetic Subjects under HAART. In this randomized, double blind, placebo controlled parallel group study, 40 HIV+ subjects were treated with rosiglitazone 4mg/day (R, n=23) or placebo (P, n=17) for 6 months. Glucose, insulin and C peptide concentrations were analyzed for assessing insulin sensitivity and secretion. Adiponectin and leptin were evaluated. Body fluid compartments were measured with bioelectrical impedance spectroscopy, and bone mineral density and body composition with Dual X Ray absorptiometry. Rosiglitazone improved peripheral insulin sensitivity (+36.7 +/- 15.7ml/min/m(2), p=0.03, means +/- SEM), while no change was observed in P (+4.5 +/- 19.5 ml/min/m(2), p=0.55). Liver insulin resistance, beta cell activity, and hepatic insulin clearance did not change. Plasma adiponectin increased (R: +2.47 +/- 0,86 mu g/ml, p=0.01 vs. P: +0.45 +/- 0.60, p=0.28). Rosiglitazone had no influence on body composition, fat distribution and bone mineral density but expanded extra-cellular fluid volume in HIV infected persons (R: +0.50 +/- 0.211, p=0.02 vs. P: 0.10 +/- 0.251, p=0.32). Lipid metabolism in P remained unchanged, in R total cholesterol and LDL cholesterol levels increased significantly (p<0.05). Rosiglitazone treatment resulted in improved peripheral insulin sensitivity with increased circulating adiponectin in HIV patients under HAART. No effect was seen on body fat distribution, bone mineral density, and weight. These side effects and their potential for cardiac risk must be weighed against the beneficial effects on glucose metabolism.