Department of Physiological Nursing, School of Nursing, University of California, 2 Koret Way, San Francisco, CA 94143, USA.
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA.
Int J Mol Sci. 2024 May 23;25(11):5684. doi: 10.3390/ijms25115684.
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 ( = 50) and placebo ( = 50) groups using Wilcoxon signed rank tests. Spearman 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，与安慰剂相比，二甲双胍治疗可使糖尿病前期成年人的 2 型糖尿病（T2D）进展风险降低 31%。循环 micro-ribonucleic acids（miRs）是 T2D 风险的有前途的生物标志物，但对于它们与二甲双胍降低 T2D 风险的方案之间的关系知之甚少。我们使用 Wilcoxon 符号秩检验比较了 DPP 二甲双胍干预组（=50）和安慰剂组（=50）亚组中 24 种循环 miR 从基线到 2 年的变化。Spearman 相关性用于评估 miR 变化与基线临床特征之间的关系。多元线性回归用于调整协变量。该样本中女性占 73%，黑人占 17%，西班牙裔占 13%，年龄为 50±11 岁。参与者肥胖、血压正常、糖尿病前期和血脂异常。调整多重比较后，与安慰剂组相比，二甲双胍组 miR 水平从基线到 2 年的变化在统计学上有显著差异：有 6 个（let-7c-5p、miR-151a-3p、miR-17-5p、miR-20b-5p、miR-29b-3p 和 miR-93-5p）显著上调，而 6 个（miR-130b-3p、miR-22-3p、miR-222-3p、miR-320a-3p、miR-320c 和 miR-92a-3p）显著下调。这些 miR 有助于解释二甲双胍如何与 T2D 风险降低相关，这可能会导致新的生物标志物、治疗方法和精准健康策略。
