Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells
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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.
|Journal||European Journal of Endocrinology. Supplement|
|Number of pages||10|
|Publication status||Published - Jan 2005|
- 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