Increased leucine turnover and insulin resistance in men with advanced HIVinfection

Background: The purpose of this study was to determine if patients with adv anced HIV infection exhibit increased rates of leucine turnover and to dete rmine dose effects of insulin on suppression of leucine turnover, We also w ished to evaluate hepatic glucose production and re-examine peripheral insu lin sensitivity in HIV infected adults, Methods: Results from 9 males with advanced HIV disease (96-121% ideal body weight, NW-AIDS) and 3 males (80-88% ideal body weight, UW-AIDS) were comp ared to age and weight matched normal volunteers (NW-C and UW-C), Each subj ect underwent basal leucine turnover studies followed by insulin dose respo nse studies using a step-up hyperinsulinemic euglycemic clamp (insulin dose : 10, 20 and 120 mU/m(2)/min) and the stable isotope [1-C-13]leucine. Hepat ic glucose production was measured using the stable isotope d-6,6(2)H(2)-gl ucose, Resting energy expenditure (REE) was measured by indirect calorimetr y and a 24-hour food recall was obtained. Viral load, Karnofsky score, and CD4 counts were measured in AIDS subjects. Results: All subjects with AIDS had higher rates of leucine appearance (leu cine Ra) than controls. Although both AIDS and Controls demonstrated suppre ssion of leucine Ra with insulin, suppression was less in AIDS subjects. Th ere was a strong relationship between leucine Ra and viral load (r = 0.87, P = 0.02), The AIDS subjects exhibited peripheral insulin resistance when c ompared to controls. Conclusions: Our results suggest that patients with HIV have both periphera l insulin resistance and resistance to the anticatabolic effects of insulin .