Alterations in the Levels of Urinary Exosomal MicroRNA-183-5p and MicroRNA-125a-5p in Individuals with Type 2 Diabetes Mellitus.

Abstract

Background: 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. Aim: To elucidate the association between urinary exosomal miRNAs and T2DM. Methods: 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. Results: 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 (p = 0.034) and miR-125a-5p (p = 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 (p = 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. Conclusions: 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.