Fang Yixuan, Sun Shiyi, Wu Jing, Liu Guanjian, Wu Qinqin, Ran Xingwu
Innovation Research Center for Diabetic Foot, Diabetic Foot Care Center, Department of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
Chinese Cochrane Centre, West China Hospital, Sichuan University, Chengdu 610041, China.
Biomedicines. 2024 Nov 14;12(11):2608. doi: 10.3390/biomedicines12112608.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder, and urinary exosomal microRNAs (miRNAs) were utilized as potential disease prediction or diagnostic biomarkers in numerous studies. This study investigated the differential expression of urinary exosomal miRNAs between non-diabetes mellitus (NDM) individuals and those with T2DM. To elucidate the association between urinary exosomal miRNAs and T2DM. : We recruited patients diagnosed with T2DM and NDM individuals in West China Hospital, Sichuan University, from November 2023 to February 2024. Subsequently, we performed sequencing of urinary exosomal microRNAs in both groups. The obtained sequencing results were further validated using RT-qPCR in both the training set and the validation set. Additionally, we conducted logistic regression analysis and Spearman correlation analysis on miRNAs with significant differential expression, as well as analysis of their biological functions. : A total of 118 urine samples were collected, 59 from individuals diagnosed with T2DM and 59 from NDM. There were differentially expressed miR-183-5p ( = 0.034) and miR-125a-5p ( = 0.008) between the two groups. Furthermore, multivariate regression analysis demonstrated that higher miR-125a-5p levels were negatively associated with the risk of T2DM ( = 0.044; OR: 0.046; 95% CI: 0.002, 0.922). Bioinformatics analysis indicated that the target genes of miR-183-5p were predominantly involved in insulin signaling and glucose transport processes, while those target genes of miR-125a-5p primarily mediated autophagy. : miR-183-5p and miR-125a-5p might be involved in the pathogenesis of T2DM, while higher urinary exosomal miR-125a-5p was negatively associated with the risk of T2DM.
2型糖尿病（T2DM）是一种代谢紊乱疾病，在众多研究中，尿外泌体微小RNA（miRNA）被用作潜在的疾病预测或诊断生物标志物。本研究调查了非糖尿病（NDM）个体与T2DM患者尿外泌体miRNA的差异表达，以阐明尿外泌体miRNA与T2DM之间的关联。我们于2023年11月至2024年2月在四川大学华西医院招募了被诊断为T2DM的患者和NDM个体。随后，我们对两组的尿外泌体微小RNA进行了测序。所获得的测序结果在训练集和验证集上均使用RT-qPCR进一步验证。此外，我们对具有显著差异表达的miRNA进行了逻辑回归分析和Spearman相关性分析，以及它们的生物学功能分析。共收集了118份尿液样本，其中59份来自被诊断为T2DM的个体，59份来自NDM个体。两组之间存在差异表达的miR-183-5p（P = 0.034）和miR-125a-5p（P = 0.008）。此外，多变量回归分析表明，较高的miR-125a-5p水平与T2DM风险呈负相关（P = 0.044；OR：0.046；95%CI：0.002，0.922）。生物信息学分析表明，miR-183-5p的靶基因主要参与胰岛素信号传导和葡萄糖转运过程，而miR-125a-5p的靶基因主要介导自噬。miR-183-5p和miR-125a-5p可能参与T2DM的发病机制，而较高的尿外泌体miR-125a-5p与T2DM风险呈负相关。
