Insulin resistance in HIV-related lipodystrophy.

Lipodystrophy (LD) associated with HIV infection is a syndrome of abnormal fat distribution observed in HIV-infected patients treated with various antiretroviral agents. In addition, insulin resistance and dyslipidemia can occur in HIV-infected patients with or without LD. The demonstration of the latter metabolic disorders in normal subjects using protease inhibitors suggests that these agents could play a causative role in their development independently of HIV status. Possible mechanisms whereby protease inhibitors can hinder insulin actions include inhibition of glucose transporter isoform Glut 4, and altered expression of leptin and tumor necrosis factor-a in adipose tissue. The presence of insulin resistance and dyslipidemia can potentially increase the risk of diabetes, cardiovascular disease, and death. However, short-term data in this regard are inconsistent. Treatment of HIV-related LD with metformin may ameliorate insulin resistance, but its impact on fat redistribution requires additional studies. Temporary cessation of antiretroviral therapy does not appear to reverse body fat changes or insulin resistance, but may partially improve the lipid profile. Further investigations are urgently needed to define the mechanisms and cardiovascular consequences of insulin resistance in HIV-related LD, and to find an effective treatment for this complex syndrome.