[Association of differentially expressed microRNAs in plasma exosomes and type 2 diabetes mellitus]

Objective: To characterize the plasma exosomal microRNA (miRNA) profile in type 2 diabetes mellitus (T2DM) patients and investigate the association of exosomal miR-122-5p expression with the disease. Methods: This study was a case-control study, and the case group was drawn from the Henan Rural Cohort and comprised T2DM patients newly diagnosed based on FPG. A 1∶1 matched control group was formed according to the principle of the same gender, same village, and age ± 3 years. The first-phase discovery set included five newly diagnosed T2DM patients and five controls, and the second-phase validation set included 72 newly diagnosed T2DM and 72 controls. miRNA profiling of plasma exosomes was performed by next-generation RNA sequencing in the discovery sets to identify differentially expressed miRNAs. Quantitative real-time PCR was used to detect the relative expression level of plasma exosomal miR-122-5p. Continuous variables were compared between the case and control groups using a t-test or a Wilcoxon rank-sum test, and categorical variables were compared using a χ² test for distribution differences. The association between plasma exosomal miR-122-5p and T2DM, as well as glucose metabolism indicators, was analyzed using logistic regression and generalized linear models. Results: Discovery set sequencing revealed 117 differentially expressed miRNAs, among which miR-122-5p was upregulated in the T2DM patients (log₂ fold change=2.12, P<0.001), and its average expression level ranked first. The validation set found that plasma exosomal miR-122-5p was upregulated in patients with T2DM (6.26) compared to controls (5.82) with a statistically significant difference (P=0.018). After adjusting for confounding factors, the risk of T2DM increased by 40.8% (OR=1.408, 95%CI: 1.002-1.978) for every 1 unit increase in the relative expression level of exosomal miR-122-5p. It was positively correlated with the insulin resistance marker triglyceride-glucose index (β=0.115, 95%CI: 0.009- 0.221). Conclusions: This study demonstrated significant changes in plasma exosomal miRNA in patients with T2DM. Among them, the relative expression level of plasma exosomal miR-122-5p was upregulated in patients with T2DM and was positively correlated with the risk of T2DM.