title: Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy.
abstract: HIV protease inhibitor-related lipodystrophy is characterized by peripheral fat loss, hyperlipidemia, and insulin resistance. Increased availability of lipid to muscle may be one of the mechanisms that induce insulin resistance. Regional fat, intramyocellular lipid (by (1)H-magnetic resonance spectroscopy), serum lipids, and insulin-stimulated glucose disposal (by hyperinsulinemic-euglycemic clamp) were quantified in 10 men who had HIV-1 infection with moderate to severe lipodystrophy and a control group of 10 nonlipodystrophic men who had HIV-1 infection and were naïve to protease inhibitors to examine the effects of lipodystrophy on glucose and lipid metabolism. Lipodystrophic subjects showed lower insulin-stimulated glucose disposal than control subjects (P = 0.001) and had increased serum triglycerides (P = 0.03), less limb fat (P = 0.02), increased visceral fat as a proportion of total abdominal fat (P = 0.003), and increased intramyocellular lipid (1.90 +/- 0.15 vs. 1.23 +/- 0.16% of water resonance peak area; P = 0.007). In both groups combined, visceral fat related strongly to intramyocellular lipid (r = 0.83, P < 0.0001) and intramyocellular lipid related negatively to insulin-stimulated glucose disposal (r = -0.71, P = 0.0005). Fasting serum cholesterol and triglycerides related positively to intramyocellular lipid and visceral fat in lipodystrophic subjects only. The data indicate that lipodystrophy is associated with increased lipid content in muscle accompanying impaired insulin action. The results do not establish causation but emphasize the interrelationships among visceral fat, myocyte lipid, and insulin action.
authors.affiliation: Metabolism and Diabetes Research Program, Garvan Institute of Medical Research, Sydney, Australia.
authors.forename: Seng Khee
authors.initials: SK
authors.lastname: Gan
authors.forename: Katherine
authors.initials: K
authors.lastname: Samaras
authors.forename: Campbell H
authors.initials: CH
authors.lastname: Thompson
authors.forename: Edward W
authors.initials: EW
authors.lastname: Kraegen
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Chisholm
mesh_terms: D015502:Absorptiometry, Photon; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology; D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000187:drug effects; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006706:Homeostasis; D006801:Humans; D019469:Indinavir / Q000009:adverse effects; D007328:Insulin / Q000502:physiology; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008060:Lipodystrophy / Q000139:chemically induced*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000009:adverse effects; D019438:Ritonavir / Q000009:adverse effects; D019258:Saquinavir / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D001786:Blood Glucose; D017320:HIV Protease Inhibitors; D007328:Insulin; D020738:Leptin; D008055:Lipids; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir