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

AIDS. 2001 Nov 9;15(16):2093-100. doi: 10.1097/00002030-200111090-00004.


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 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-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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Body Composition
  • Dideoxynucleosides / therapeutic use
  • Drug Therapy, Combination
  • Fatty Acids / blood
  • Glucose / metabolism
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / physiology
  • Humans
  • Insulin Resistance*
  • Lipodystrophy / chemically induced
  • Lipodystrophy / metabolism*
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / therapeutic use


  • Anti-HIV Agents
  • Dideoxynucleosides
  • Fatty Acids
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Glucose
  • abacavir