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Session 94 Poster Presentations
Pathogenesis and Mechanisms of Lipodystrophy Syndromes
Session Day and Time: Thursday 1:30 - 3:30 pm
Room: Hall B


757
Impaired Insulin Sensitivity in HIV-infected Individuals is Associated with Higher Hepatic Lipid Content and Visceral Adiposity
K. Yarasheski*, D. Reeds, J. Schulte, E. Zinna, S. Claxton, S. Mohammed, D. Yablonskiy, L. Bretthorst, W. Powderly, S. Klein
Washington Univ, St Louis, MO

Background: In an ongoing cross sectional study of HIV-infected individuals with metabolic complications, we are examining the relationship between impaired insulin sensitivity and lipid content of the liver and abdomen. We hypothesized that impaired insulin sensitivity would be associated with higher hepatic lipid content and visceral adiposity.

Methods: We studied 14 Caucasian men and 1 African American woman infected with HIV (mean age 42 yr; 21% body fat; median CD4 = 571 c/µL; VL < 400 c/mL; 2 were medication naïve; 7 were receiving non-PI regimens; and 6 were receiving PI-HAART). We used a 2-stage hyperinsulinemic (20 and 50 mU insulin/m2/min)-euglycemic clamp and measured insulin sensitivity as the rate of glucose infusion (mg glucose/kg FFM/min) required to maintain plasma glucose levels at 5.5 mM. Hepatic lipid content was measured using localized 1H-magnetic resonance spectroscopy (TE = 23 and 53msec) for 3 voxels within the left and right lobes of the liver. Visceral (VAT) and abdominal subcutaneous adipose tissue (SAT) images were obtained using 8-slice axial 1H-MR imaging and the areas quantified using Analyze 4.0 software. Kendall’s tau nonparametric test was used to evaluate correlations.

Results: During the clamp, insulin levels and insulin sensitivity were Stage 1: 250 pM and 3.0 mg glucose/kg FFM/min; Stage 2: 560 pM and 8.0. Median VAT and SAT were 15.2 and 13.6 cm2. Median hepatic lipid content was 4.9% relative to the hepatic water resonance. Hepatic lipid content (p < 0.03; r = 0.45) and VAT (p < 0.02; r = 0.50) were significantly correlated with insulin sensitivity. Hepatic lipid content < 4% and VAT < 18cm2 were associated with normal insulin sensitivity.

Conclusions: Hepatic and intra-abdominal lipid deposition are strong predictors of insulin resistance in non-obese HIV-infected people. This suggests that lipid accumulation (e.g., lipotoxicity) in non-adipose tissues (e.g., liver, muscle, heart) may mediate central and peripheral insulin resistance. The cause of hepatic lipid accumulation is under investigation.