High Irisin levels in nondiabetic HIV-infected males are associated with insulin resistance, nonalcoholic fatty liver disease, and subclinical atherosclerosis

ObjectiveHIV infection is associated with an increased risk of cardiovascular disease. Irisin is a miokyne secreted by skeletal muscle, which may influence insulin homeostasis, nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. Our objective was to evaluate the relationships between serum irisin, insulin homeostasis, NAFLD and subclinical atherosclerosis in HIV-infected males. DesignCross-sectional study in a cohort of HIV-infected patients. PatientsInclusion criteria: men older than 18years; antiretroviral therapy (ART) -naive or on effective ART (<50 HIV-1 RNAcopies/mL) without changes in the previous 6months; no diabetes or hepatitis C. MeasurementsIrisin was measured by enzymatic immunoassay (Phoenix Pharmaceuticals), insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR), as well as the 2-hour continuous infusion of glucose with model assessment (CIGMA-HOMA). Hepatic steatosis was measured by 1-H magnetic resonance spectroscopy, subclinical atherosclerosis by evaluation of carotid intima-media thickness (C-IMT), measured by Ultrasonography. ResultsEight nine men (age 42.08.3years, duration of HIV infection 7.9 +/- 5.6years, CD4 count 547 +/- 279cells/mL) were included. Circulating irisin was positively related to HOMA-IR and CIGMA-HOMA, hepatic triglyceride content, and to VAT/SAT ratio. Higher irisin concentrations were associated with higher C-IMT, although this association did not persist in multivariate analysis. Lipodystrophy and a higher baseline PAI-1 concentration were independently associated with C-IMT. ConclusionsIn male HIV patients without diabetes, higher irisin concentrations are positively associated with insulin resistance, NAFLD and subclinical atherosclerosis. However, waist-hip-ratio is the main determinant of insulin resistance, and PAI-1 and lipodystrophy were the strongest determinants of IMT in this population.