title: Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases, Hvidovre University Hospital, Copenhagen, Denmark. sbhau@dadlnet.dk
authors.forename: Steen B
authors.initials: SB
authors.lastname: Haugaard
authors.forename: Ove
authors.initials: O
authors.lastname: Andersen
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Heidi
authors.initials: H
authors.lastname: Storgaard
authors.forename: Mogens
authors.initials: M
authors.lastname: Fenger
authors.forename: Johan
authors.initials: J
authors.lastname: Iversen
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D000328:Adult; D000409:Alanine / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D006678:HIV; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D014316:Tritium
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D014316:Tritium; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D000409:Alanine; D005990:Glycerol