Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells

Steen B Haugaard, Ove Andersen, Flemming Dela, Jens Juul Holst, Heidi Storgaard, Mogens Fenger, Johan Iversen, Sten Madsbad

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Abstract

OBJECTIVES: Lipodystrophy and insulin resistance are prevalent among human immunodeficiency virus (HIV)-infected patients on combined antiretroviral therapy (HAART). Aiming to provide a detailed description of the metabolic adverse effects of HIV-lipodystrophy, we investigated several aspects of glucose metabolism, lipid metabolism and beta-cell function in lipodystrophic HIV-infected patients.

METHODS: [3-3H]glucose was applied during euglycaemic hyperinsulinaemic clamps in association with indirect calorimetry in 43 normoglycaemic HIV-infected patients (18 lipodystrophic patients on HAART (LIPO), 18 patients without lipodystrophy on HAART (NONLIPO) and seven patients who were naive to antiretroviral therapy (NAIVE) respectively). beta-cell function was evaluated by an intravenous glucose tolerance test.

RESULTS: Compared with NONLIPO and NAIVE separately, LIPO displayed markedly reduced ratio of limb to trunk fat (RLF; > 34%, P < 0.001), hepatic insulin sensitivity (> 40%, P < 0.03), incremental glucose disposal (>50%, P < 0.001) and incremental exogenous glucose storage (>50%, P < 0.05). Furthermore, LIPO displayed reduced incremental glucose oxidation (P < 0.01), increased clamp free fatty acids (P < 0.05) and attenuated insulin-mediated suppression of lipid oxidation (P < 0.05) compared with NONLIPO. In combined study groups, RLF correlated with hepatic insulin sensitivity (r = 0.69), incremental glucose disposal (r = 0.71) and incremental exogenous glucose storage (r = 0.40), all P < 0.01. Disposition index (i.e. first-phase insulin response to intravenous glucose multiplied by incremental glucose disposal) was reduced by 46% (P = 0.05) in LIPO compared with the combined groups of NONLIPO and NAIVE, indicating an impaired adaptation of beta-cell function to insulin resistance in LIPO.

CONCLUSION: Our data suggest that normoglycaemic lipodystrophic HIV-infected patients display impaired glucose and lipid metabolism in multiple pathways involving liver, muscle tissue and beta-cell function.

Original languageEnglish
JournalEuropean Journal of Endocrinology. Supplement
Volume152
Issue number1
Pages (from-to)103-12
Number of pages10
ISSN0804-4643
Publication statusPublished - Jan 2005

Keywords

  • Adult
  • Alanine
  • Antiretroviral Therapy, Highly Active
  • Blood Glucose
  • Body Composition
  • Cholesterol, HDL
  • Fatty Acids, Nonesterified
  • Glucagon
  • Glucose
  • Glycerol
  • HIV
  • HIV-Associated Lipodystrophy Syndrome
  • Humans
  • Insulin
  • Islets of Langerhans
  • Lactic Acid
  • Liver
  • Male
  • Middle Aged
  • Muscle, Skeletal
  • Triglycerides
  • Tritium

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