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% male) enrolled in the Alcohol & Metabolic Comorbidities in PLWH: Evidence-Driven Interventions (ALIVE-Ex) study were stratified into negative phosphatidylethanol (PEth<8ng/ml, N=42) and positive PEth (PEth≥8ng/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, miR-206), pancreatic β-cell (miR-375), liver (miR-20a), and adipose tissue (miR-let-7b, miR-146a, miR-221) function. Correlation and multiple regression analyses between miR expression and adiponectin, 2h glucose, insulin, and C-peptide values were performed adjusting for 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 2h 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 2h 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.
Reduced Serum Osteocalcin in High‐Risk Alcohol Using People Living With HIV Does Not Correlate With Systemic Oxidative Stress or Inflammation: Data From the New Orleans Alcohol Use in HIV Study