Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Physiol Genomics. 2022 Jan 1;54(1):36-44. doi: 10.1152/physiolgenomics.00085.2021. Epub 2021 Dec 3.
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 ( = 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, = 42) and positive PEth (PEth ≥ 8 ng/mL, = 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 ( = 0.002) in the negative PEth group, and miR-20a was positively associated with 2 h glucose ( = 0.013) in the positive PEth group. Regression analyses combining miRs demonstrated that miR-133a ( < 0.001) and miR-221 ( = 0.010) together predicted adiponectin in the negative PEth group. miR-20a ( < 0.001) and miR-375 ( = 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.
艾滋病毒感染者（PLWH）合并症的发病率较高，包括胰岛素抵抗和有风险的酒精使用。循环 microRNAs（miRs）可能是生理病理状态的微创指标。我们旨在确定酒精是否调节循环 miR 与 PLWH 葡萄糖/胰岛素动力学测量的关联。在酒精和代谢合并症在 PLWH 中的证据驱动干预（ALIVE-Ex）研究中，将 PLWH（=96；69.8%男性）分为阴性磷脂酰乙醇（PEth < 8ng/mL，=42）和阳性 PEth（PEth≥8ng/mL，=54）组。进行口服葡萄糖耐量试验（OGTT），并从空腹血浆中分离总 RNA 以确定绝对 miR 表达。根据其在骨骼肌（miR-133a 和 miR-206）、胰腺β细胞（miR-375）、肝脏（miR-20a）和脂肪组织（miR-let-7b、miR-146a 和 miR-221）功能中的作用选择循环 miR。调整体重指数（BMI）类别、年龄、性别和病毒载量后，对 miR 表达与脂联素、2 h 血糖、胰岛素和 C 肽值之间的相关性和多元回归分析进行了分析。miR-133a 与阴性 PEth 组的脂联素呈负相关（=0.002），miR-20a 与阳性 PEth 组的 2 h 血糖呈正相关（=0.013）。将 miRs 结合起来的回归分析表明，miR-133a（<0.001）和 miR-221（=0.010）共同预测阴性 PEth 组的脂联素。miR-20a（<0.001）和 miR-375（=0.002）共同预测阳性 PEth 组的 2 h 血糖。我们的结果表明，miRs 与葡萄糖/胰岛素动力学测量之间的关联在 PEth 组之间有所不同，这表明导致 PLWH 葡萄糖稳态改变的病理生理机制可能受到酒精使用的调节。
