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      Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy.

      AIDS (London, England)
      Adiponectin, Adipose Tissue, immunology, Adult, Aged, Anti-HIV Agents, therapeutic use, Antigens, CD, blood, Antiretroviral Therapy, Highly Active, Apolipoproteins A, analysis, Apolipoproteins B, C-Reactive Protein, Cholesterol, Cytokines, HIV Infections, drug therapy, HIV-1, HIV-Associated Lipodystrophy Syndrome, Humans, Intercellular Signaling Peptides and Proteins, Interleukin-6, Leptin, Male, Middle Aged, Proteins, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Regression Analysis, Triglycerides, Tumor Necrosis Factor-alpha

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          Abstract

          Adipocytokines, secreted by adipose tissue, may regulate fat metabolism, lipid and glucose homeostasis and insulin sensitivity. We analysed the relations between circulating concentrations of adiponectin, leptin, interleukin-6, tumor necrosis factor alpha and its soluble receptors sTNFR1 and R2, lipodystrophic phenotypes and metabolic alterations in patients under highly active antiretroviral therapy (HAART). We studied 131 consecutive HIV-infected males under protease inhibitor (PI)-based HAART, with body mass index < 27 kg/m2 and C-reactive protein (CRP) < 10 mg/l. Patients were classified in four groups according to clinical examination: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). In addition to adipocytokines, we measured plasma fasting levels of triglycerides, cholesterol, cardiovascular risk markers (high-sensitivity CRP and apolipoproteins B/A1 ratio), fasted and 2 h post-glucose loading glycemia and insulinemia and calculated the quantitative insulin sensitivity check index. The patients were HIV-infected and PI-treated for a mean of 8.2 and 1.6 years respectively; 74% presented lipodystrophy, 38% altered glucose tolerance and 42% hypertriglyceridemia. Insulin sensitivity correlated positively with adiponectin and negatively with leptin and interleukin-6. Adiponectin, but not leptin, negatively correlated with all metabolic parameters. Insulin resistance, metabolic defects and cardiovascular risk markers were strongly negatively correlated with the adiponectin/leptin ratio (A/L), and positively with sTNFR1. LA patients had a longer duration of infection but ML patients presented the most severe metabolic alterations, insulin resistance and A/L decrease. These results suggest that adiponectin and the TNFalpha system are related to lipodystrophy, insulin resistance and metabolic alterations in patients under PI-based HAART. A/L and sTNFR1 could predict insulin sensitivity and potential cardiovascular risk in these patients.

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