BACKGROUND: Treatment for HIV-1 infection is complicated by fat redistribution (lipodystrophy). This is associated with insulin resistance concerning glucose uptake. Our aim was to characterize glucose metabolism more comprehensively 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 insulin. METHODS:Six HIV-1-infected men onprotease inhibitor-based HAART with lipodystrophy (HIV+LD) were studied. The results were compared with those in six matched healthy male volunteers. Insulin sensitivity was quantified by hyperinsulinemic euglycaemic clamp. Glucose production and uptake were assessed 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 production was suppressed by 53% in HIV+LD, but by 85% in controls (P = 0.004). Glucose disposal increased in both groups, but by only 27% in HIV+LD versus 201% in controls (P = 0.004). Consequently, insulin-stimulated total glucose disposal was lower in HIV+LD patients (P = 0.006). Non-oxidative glucose disposal as percentage of total disposal did not differ significantly between groups (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-infected patients with lipodystrophy. Moreover, both the ability of insulin to suppress endogenous glucose production and lipolysis, and to stimulate peripheral glucose uptake and its metabolic pathways is reduced, indicating severe resistance concerning multiple effects of insulin.
RCT Entities:
BACKGROUND: Treatment for HIV-1 infection is complicated by fat redistribution (lipodystrophy). This is associated with insulin resistance concerning glucose uptake. Our aim was to characterize glucose metabolism more comprehensively in HIV-1-infectedpatients 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 insulin. METHODS: Six HIV-1-infectedmen on protease inhibitor-based HAART with lipodystrophy (HIV+LD) were studied. The results were compared with those in six matched healthy male volunteers. Insulin sensitivity was quantified by hyperinsulinemic euglycaemic clamp. Glucose production and uptake were assessed 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 production was suppressed by 53% in HIV+LD, but by 85% in controls (P = 0.004). Glucose disposal increased in both groups, but by only 27% in HIV+LD versus 201% in controls (P = 0.004). Consequently, insulin-stimulated total glucose disposal was lower in HIV+LD patients (P = 0.006). Non-oxidative glucose disposal as percentage of total disposal did not differ significantly between groups (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-infectedpatients with lipodystrophy. Moreover, both the ability of insulin to suppress endogenous glucose production and lipolysis, and to stimulate peripheral glucose uptake and its metabolic pathways is reduced, indicating severe resistance concerning multiple effects of insulin.
Authors: Georg M N Behrens; Anne-Rose Boerner; Klaus Weber; Joerg van den Hoff; Johann Ockenga; Georg Brabant; Reinhold E Schmidt Journal: J Clin Invest Date: 2002-11 Impact factor: 14.808
Authors: Oliver P Flint; Mustafa A Noor; Paul W Hruz; Phil B Hylemon; Kevin Yarasheski; Donald P Kotler; Rex A Parker; Aouatef Bellamine Journal: Toxicol Pathol Date: 2009-01-26 Impact factor: 1.902
Authors: Wen Guo; Siu Wong; Jeffrey Pudney; Ravi Jasuja; Ning Hua; Lan Jiang; Andrew Miller; Paul W Hruz; James A Hamilton; Shalender Bhasin Journal: Arterioscler Thromb Vasc Biol Date: 2009-09-17 Impact factor: 8.311