Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia.
Dyslipidemia is common in patients with HIV infection. In this study, a two-stage euglycemic hyperinsulinemic clamp, with infusion of stable isotopically labeled tracers, was used to evaluate insulin action in skeletal muscle, liver, and adipose tissue in HIV-infected men with dyslipidemia (HIV-DL; plasma triglyceride >250 mg/dl and HDL <45 mg/dl; n=12), HIV-infected men without dyslipidemia (HIV w/o DL; n=12), and healthy men (n=6). Basal rates of glucose production (glucose R(a)), glucose disposal (glucose R(d)), and lipolysis (palmitate R(a)) were similar between groups. The relative suppression of glucose R(a) (63+/- 4, 77+/- 2, and 78+/- 3%, P=0.008) and palmitate R(a) (49+/-4, 63+/-3, and 68+/-3%, P=0.005) during ow-dose insulin infusion (plasma insulin approximately 30 microU/ml), and the relative stimulation of glucose R(d) (214+/-21, 390+/-25, and 393+/-46%, P=0.001) during high-dose insulin infusion (plasma insulin approximately 75 microU/ml) were lower in HIV-DL than in HIV w/o DL and healthy volunteers, respectively. Suppression of basal glucose R(a) correlated with plasma adiponectin (r=0.44, P=0.02) and inversely with plasma IL-6 (r=-0.49, P<0.001). Stimulation of glucose R(d) correlated directly with adiponectin (r=0.48, P<0.01) and inversely with IL-6 (r=-0.49, P=0.02). We conclude that dyslipidemia in HIV-infected men is indicative of multiorgan insulin resistance, and circulating adipokines may be important in the pathogenesis of impaired insulin action.
Reeds
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Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, USA. dreeds@im.wustl.edu
Yarasheski
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Fontana
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Cade
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Laciny
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DeMoss
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Patterson
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Powderly
W G
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Klein
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D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood* / Q000150:complications; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D019308:Palmitic Acid / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D019308:Palmitic Acid; D005947:Glucose