A rosiglitazone-induced increase in adiponectin does not improve glucose metabolism in HIV-infected patients with overt lipoatrophy

HIV-infected patients on antiretroviral therapy frequently develop changes in body fat distribution and disturbances in glucose metabolism, associated with reduced adiponectin levels. As adiponectin, principally the HMW (high-molecular-weight) form, has insulin sensitizing properties, we investigated the effects of an increase in adiponectin on glucose metabolism in HIV-lipodystrophy. In this randomized, double-blind, placebo-controlled trial, we included HIV-1-infected patients with severe lipoatrophy, with an undetectable viral load and who had received neither protease inhibitors nor stavudine for >/=6 months. Patients were randomized to rosiglitazone (8 mg daily (N=8)) to increase adiponectin levels or placebo (N=5) for 16 weeks. Peripheral glucose disposal, glucose production and lipolysis were measured after an overnight fast and during a hyperinsulinemic-euglycemic clamp using stable isotopes. Body composition was assessed by CT and DEXA. Although body fat distribution was unaffected, rosiglitazone increased total plasma adiponectin levels by 107% (p<0.02) and the ratio of HMW to total adiponectin by 73% (p<0.001). In the placebo group, neither total adiponectin levels (p=0.62), nor the ratio of HMW to total adiponectin changed (p=0.94). The marked increase in adiponectin induced by rosiglitazone was not associated with significant changes in basal endogenous glucose production (p=0.90), basal lipolysis (p=0.90), insulin-mediated suppression of glucose production (p=0.17) and lipolysis (p=0.54) nor with changes in peripheral glucose disposal (p=0.13). Acknowledging the limited statistical power of our small study, these findings if confirmed by larger studies, could question the importance of adiponectin in regulating glucose metabolism in HIV-lipodystrophy. Key words: insulin resistance, adipocytokines, HIV-associated lipodystrophy.