Abstract
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 4 mg/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±15.7 ml/min/m2 , p=0.03, means±SEM), while no change was observed in P (+4.5±19.5 ml/min/m2 , p=0.55). Liver insulin resistance, beta cell activity, and hepatic insulin clearance
did not change. Plasma adiponectin increased (R: +2.47±0.86 μg/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±0.21 l, p=0.02 vs. P: 0.10±0.25 l, 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.
Key words
lipodystrophy - adiponectin - leptin
References
Correspondence
bernhard.ludvik@meduniwien.ac.at
