Chronic binge alcohol administration impairs glucose-insulin dynamics and decreases adiponectin in asymptomatic simian immunodeficiency virus-infected macaques

Abstract

Alcohol use disorders (AUDs) frequently exist among persons living with HIV/AIDS. Chronic alcohol consumption, HIV infection, and antiretroviral therapy (ART) are independently associated with impairments in glucose-insulin dynamics. Previous studies from our laboratory have shown that chronic binge alcohol (CBA) administration decreases body mass index, attenuates weight gain, and accentuates skeletal muscle wasting at end-stage disease in non-ART-treated simian immunodeficiency virus (SIV)-infected male rhesus macaques. The aim of this study was to investigate whether CBA and ART alone or in combination alter body composition or glucoseinsulin dynamics in SIV-infected male rhesus macaques during the asymptomatic phase of SIV infection. Daily CBA or sucrose (SUC) administration was initiated 3 mo before intrarectal SIV inoculation and continued until the study end point at 11 mo post-SIV infection. ART or placebo was initiated 2.5 mo after SIV infection and continued until study end point. Four treatment groups (SUC/SIV ± ART and CBA/ SIV ± ART) were studied. CBA/SIV macaques had significantly decreased circulating adiponectin and resistin levels relative to SUC/SIV macaques and reduced disposition index and acute insulin response to glucose, insulin, and C-peptide release during frequently sampled intravenous glucose tolerance test, irrespective of ART status. No statistically significant differences were observed in homeostatic model assessmentinsulin resistance values, body weight, total body fat, abdominal fat, or total lean mass or bone health among the four groups. These findings demonstrate CBA-mediated impairments in glucose-insulin dynamics and adipokine profile in asymptomatic SIV-infected macaques, irrespective of ART.