Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways

Background: Treatment for HIV-1 infection is complicated by fat redistribut ion (lipodystrophy). This is associated with insulin resistance concerning glucose uptake. Our aim was to characterize glucose metabolism more compreh ensively in HIV-1-infected patients with lipodystrophy. We assessed glucose disposal and its pathways, glucose production, plasma free fatty acid (FFA ) levels, and the degree to which these parameters could be suppressed by i nsulin. Methods: Six HIV-1-infected men on protease inhibitor-based HAART with lipo dystrophy (HIV+LD) were studied. The results were compared with those in si x matched healthy male volunteers. Insulin sensitivity was quantified by hy perinsulinemic euglycaemic clamp. Glucose production and uptake were assess ed by tracer dilution employing 6,6D(2)-glucose. Results: At post-absorptive insulin concentrations, glucose production was 47% higher in HIV+LD than controls (P=0.025). During clamp, glucose product ion was suppressed by 53% in HIV+LD, but by 85% in controls (P=0.004). Gluc ose disposal increased in both groups, but by only 27% in HIV+LD versus 201 % in controls (P=0.004). Consequently, insulin-stimulated total glucose dis posal was lower in HIV+LD patients (P=0.006). Non-oxidative glucose disposa l as percentage of total disposal did not differ significantly between grou ps (63% in HIV+LD and 62% in controls). Baseline plasma FFA concentrations were higher (0.60 versus 0.35 mmol/l; P=0.024), whereas FFA decline during hyperinsulinemia was less (65 versus 85%; P=0.01) in HIV+LD versus controls . Conclusions: Post-absorptive glucose production is increased in HIV-1-infec ted patients with lipodystrophy. Moreover, both the ability of insulin to s uppress endogenous glucose production and lipolysis, and to stimulate perip heral glucose uptake and its metabolic pathways is reduced, indicating seve re resistance concerning multiple effects of insulin. (C) 2001 Lippincott W illiams & Wilkins.