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- Title
Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic {szligbeta}-cells.
- Authors
Steen B Haugaard; Ove Andersen; Flemming Dela; Jens Juul Holst; Heidi Storgaard; Mogens Fenger; Johan Iversen; Sten Madsbad
- 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 {szligbeta}-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 nave to antiretroviral therapy (NAVE) respectively). {szligbeta}-cell function was evaluated by an intravenous glucose tolerance test. RESULTS: Compared with NONLIPO and NAVE 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 NAVE, indicating an impaired adaptation of {szligbeta}-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 {szligbeta}-cell function.
- Subjects
HYPOGLYCEMIC agents; PANCREATIC secretions; LIPID metabolism; BIOCHEMISTRY
- Publication
European Journal of Endocrinology, 2005, Vol 152, Issue 1, p103
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/eje.1.01835