Lewis Kimberly A, Stroebel Benjamin, Zhang Li, Aouizerat Bradley, Mattis Aras, Flowers Elena
University of California San Francisco.
New York University.
Res Sq. 2024 Jan 16:rs.3.rs-3846347. doi: 10.21203/rs.3.rs-3846347/v1.
The Diabetes Prevention Program (DPP) randomized controlled trial demonstrated that metformin treatment reduced progression to type 2 diabetes (T2D) by 31% compared to placebo in adults with prediabetes. Circulating micro-ribonucleic acids (miRs) are promising biomarkers of T2D risk, but little is known about their associations with metformin regimens for T2D risk reduction. We compared the change in 24 circulating miRs from baseline to 2 years in a subset from DPP metformin intervention (n = 50) and placebo (n = 50) groups using Wilcoxon signed rank tests. Spearman's correlations were used to evaluate associations between miR change and baseline clinical characteristics. Multiple linear regression was used to adjust for covariates. The sample was 73% female, 17% Black, 13% Hispanic, and 50 ± 11 years. Participants were obese, normotensive, prediabetic, and dyslipidemic. Change in 12 miR levels from baseline to 2 years was significantly different in the metformin group compared with placebo after adjusting for multiple comparisons: six (let-7c-5p, miR-151a-3p, miR-17-5p, miR-20b-5p, miR-29b-3p, and miR-93-5p) were significantly upregulated and six (miR-130b-3p, miR-22-3p, miR-222-3p, miR-320a-3p, miR-320c, miR-92a-3p) were significantly downregulated in the metformin group. These miRs help to explain how metformin is linked to T2D risk reduction, which may lead to novel biomarkers, therapeutics, and precision-health strategies.
糖尿病预防计划（DPP）随机对照试验表明，在患有糖尿病前期的成年人中，与安慰剂相比，二甲双胍治疗可使2型糖尿病（T2D）的进展降低31%。循环微小核糖核酸（miRs）是T2D风险的有前景的生物标志物，但关于它们与降低T2D风险的二甲双胍治疗方案之间的关联知之甚少。我们使用Wilcoxon符号秩检验比较了DPP二甲双胍干预组（n = 50）和安慰剂组（n = 50）亚组中从基线到2年的24种循环miRs的变化。Spearman相关性用于评估miR变化与基线临床特征之间的关联。多元线性回归用于调整协变量。样本中73%为女性，17%为黑人，13%为西班牙裔，年龄为50±11岁。参与者肥胖、血压正常、患有糖尿病前期且血脂异常。在进行多重比较调整后，二甲双胍组与安慰剂组相比，从基线到2年的12种miR水平变化有显著差异：六种（let-7c-5p、miR-151a-3p、miR-17-5p、miR-20b-5p、miR-29b-3p和miR-93-5p）在二甲双胍组中显著上调，六种（miR-130b-3p、miR-22-3p、miR-222-3p、miR-320a-3p、miR-320c、miR-92a-3p）在二甲双胍组中显著下调。这些miRs有助于解释二甲双胍与降低T2D风险之间的联系，这可能会带来新的生物标志物、治疗方法和精准健康策略。
