Improved Insulin Sensitivity and Body Fat Distribution in HIV-Infected Patients Treated With Rosiglitazone: A Pilot Study

Abstract

The insulin-sensitizing drugs thiazolidinediones (TZDs), such as rosiglitazone, improve insulin sensitivity and also promote adipocyte differentiation in vitro. The authors hypothesized that TZDs might be beneficial to patients with HIV disease to improve insulin sensitivity and the distribution of body fat by increasing peripheral fat. The ability of rosiglitazone (8 mg/d) to improve insulin sensitivity (from hyperinsulinemic-euglycemic clamp) and to improve body fat distribution (determined from computed tomography measurements of visceral adipose tissue [VAT] and subcutaneous adipose tissue [SAT]) was determined in 8 HIV-positive patients. Before treatment, the insulin sensitivity of the patients was reduced to approximately 34% of that in control subjects. The rate of glucose disposal during a hyperinsulinemic-euglycemic clamp (Rd) was 3.8 +/-.4 (SEM) mg glucose/kg lean body mass/min compared with 11.08 +/- 1.1 (p<.001) in healthy age- and body mass index (BMI)-matched control subjects. After rosiglitazone treatment of 6 to 12 weeks, Rd increased to 5.99 +/-.9 (p=.02), an improvement of 59 +/- 22%. SAT increased by 23 +/- 10% (p=.05), and, surprisingly, VAT was decreased by 21 +/- 8% (p=.04) with a trend for increased SAT/VAT that failed to reach statistical significance. There were no significant changes in blood counts, viral loads, or CD4 counts with rosiglitazone treatment. The study demonstrates that rosiglitazone therapy improves insulin resistance and body fat distribution in some patients with HIV disease.

Diabetes and HIV

“…> Thiazolidinediones: theoretically these drugs could be of benefi t in those with lipodystrophy, given the known effects that they have on promoting adipocyte differentiation; however, clinical reports have been disappointing. 15 …”

Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications

“…Indeed rosiglitazone has been shown to improve insulin resistance in patients with HIV associated metabolic syndrome, however at the expense of increased triglyceride and cholesterol concentrations [129][130][131][132] . Regarding fat redistribution the initially encouraging results reporting a beneficial effect of rosiglitazone in body fat gain [129,130] were not seen during two other studies including a recent larger (n=108) placebo controlled study [131] evaluating rosiglitazone in lipoatrophic HIV patients [131,132] .…”

“…Regarding fat redistribution the initially encouraging results reporting a beneficial effect of rosiglitazone in body fat gain [129,130] were not seen during two other studies including a recent larger (n=108) placebo controlled study [131] evaluating rosiglitazone in lipoatrophic HIV patients [131,132] . This has led to the speculation that rosiglitazone may exert its insulin sensitizing effects without increasing the subcutaneous adipose tissue mass [132] .…”

Carotid Intima Media Thickness, Inflammatory Markers, and Endothelial Activation Markers in HIV Patients with Lipoatrophy Increased at 48 Weeks Regardless of Use of Rosiglitazone or Placebo

“…The thiazolidenedione rosiglitazone is a potent agonist of PPAR-g and thus may be a promising additional therapeutic option for these individuals. [14][15][16][17][18][19][20] However, a recent publication has questioned an association between MI and rosiglitazone in diabetics raising concern regarding its use. 21 Subsequent studies led to conflicting results.…”