Details

Autor(en) / Beteiligte

• Gan, Seng Khee
• Samaras, Katherine
• Thompson, Campbell H
• Kraegen, Edward W
• Carr, Andrew
• Cooper, David A
• Chisholm, Donald J

Titel

Altered Myocellular and Abdominal Fat Partitioning Predict Disturbance in Insulin Action in HIV Protease Inhibitor-Related Lipodystrophy

Ist Teil von

• Diabetes (New York, N.Y.), 2002-11, Vol.51 (11), p.3163-3169

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• Altered Myocellular and Abdominal Fat Partitioning Predict Disturbance in Insulin Action in HIV Protease Inhibitor-Related Lipodystrophy Seng Khee Gan 1 , Katherine Samaras 1 , Campbell H. Thompson 2 , Edward W. Kraegen 1 , Andrew Carr 3 , David A. Cooper 3 4 and Donald J. Chisholm 1 1 Metabolism and Diabetes Research Program, Garvan Institute of Medical Research, Sydney, Australia 2 Department of Biochemistry, University of Sydney, Sydney, Australia 3 HIV Medicine Unit and Centre for Immunology, St. Vincent’s Hospital, Sydney, Australia 4 National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia 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. Footnotes Address correspondence and reprint requests to Donald J. Chisholm, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia. E-mail: d.chisholm{at}garvan.org.au . Received for publication 27 November 2001 and accepted in revised form 26 July 2002. DEXA, dual-energy X-ray absorptiometry; EMCH, extramyocellular CH; EMCL, extramyocellular lipid; HAART, highly active antiretroviral therapy; 1 H-MRS, 1 H-magnetic resonance spectroscopy; HOMA-IR, homeostasis model assessment for insulin resistance; IGT, impaired glucose tolerance; IMCH, intramyocellular CH; IMCL, intramyocellular lipid; MRI, magnetic resonance imaging; SAT, subcutaneous abdominal adipose tissue; TAT, total abdominal adipose tissue; VAT, visceral adipose tissue DIABETES