Unique circulating microRNA associations with dysglycemia in people living with HIV and alcohol use

Abstract

People living with HIV (PLWH) have increased prevalence of comorbid conditions including insulin resistance and at-risk alcohol use. Circulating microRNAs (miRs) may serve as minimally invasive indicators of pathophysiological states. We aimed to identify whether alcohol modulates circulating miR associations with measures of glucose/insulin dynamics in PLWH. PLWH ( n = 96; 69.8% males) enrolled in the Alcohol & Metabolic Comorbidities in PLWH: Evidence-Driven Interventions (ALIVE-Ex) study were stratified into negative phosphatidylethanol (PEth < 8 ng/mL, n = 42) and positive PEth (PEth ≥ 8 ng/mL, n = 54) groups. An oral glucose tolerance test (OGTT) was administered, and total RNA was isolated from fasting plasma to determine absolute miR expression. Circulating miRs were selected based on their role in skeletal muscle (miR-133a and miR-206), pancreatic β-cell (miR-375), liver (miR-20a), and adipose tissue (miR-let-7b, miR-146a, and miR-221) function. Correlation and multiple regression analyses between miR expression and adiponectin, 2 h glucose, insulin, and C-peptide values were performed adjusting for body mass index (BMI) category, age, sex, and viral load. miR-133a was negatively associated with adiponectin ( P = 0.002) in the negative PEth group, and miR-20a was positively associated with 2 h glucose ( P = 0.013) in the positive PEth group. Regression analyses combining miRs demonstrated that miR-133a ( P < 0.001) and miR-221 ( P = 0.010) together predicted adiponectin in the negative PEth group. miR-20a ( P < 0.001) and miR-375 ( P = 0.002) together predicted 2 h glucose in the positive PEth group. Our results indicate that associations between miRs and measures of glucose/insulin dynamics differed between PEth groups, suggesting that the pathophysiological mechanisms contributing to altered glucose homeostasis in PLWH are potentially modulated by alcohol use.