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Increased leucine turnover and insulin resistance in men with advanced HIV infection
D S Hardin1, A LeBlanc, D Young
1Department of Pediatrics, University of Texas Health Science Center, Houston 77030, USA.
Background:
The purpose of this study was to determine if patients with advanced HIV infection exhibit increased rates of leucine turnover and to determine dose effects of insulin on suppression of leucine turnover. We also wished to evaluate hepatic glucose production and re-examine peripheral insulin 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 compared to age and weight matched normal volunteers (NW-C and UW-C). Each subject underwent basal leucine turnover studies followed by insulin dose response studies using a step-up hyperinsulinemic euglycemic clamp (insulin dose: 10, 20 and 120 mU/m2/min) and the stable isotope [1-13C]leucine. Hepatic glucose production was measured using the stable isotope d-6,6(2)H2-glucose. Resting energy expenditure (REE) was measured by indirect calorimetry 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 (leucine Ra) than controls. Although both AIDS and Controls demonstrated suppression of leucine Ra with insulin, suppression was less in AIDS subjects. There was a strong relationship between leucine Ra and viral load (r = 0.87, P = 0.02). The AIDS subjects exhibited peripheral insulin resistance when compared to controls.
Conclusions:
Our results suggest that patients with HIV have both peripheral insulin resistance and resistance to the anticatabolic effects of insulin.