[Association of plasma exosomal miR-372-3p with type 2 diabetes mellitus]

Objective: To explore the association between plasma exosomal miR-372-3p level and type 2 diabetes mellitus (T2DM). Methods: Based on the "Henan Rural Cohort", a discovery set (5 pairs of newly diagnosed T2DM patients and controls matched by gender and age ±3 years) and a validation set (67 pairs of newly diagnosed T2DM patients and controls matched by the same conditions) were established. In the discovery set, small RNA sequencing was performed to screen for differentially expressed miRNAs. In the validation set, the plasma exosomal level of miR-372-3p was detected using quantitative real-time PCR. Conditional logistic regression models and linear regression analysis models were employed to assess the associations of plasma exosomal miR-372-3p level with T2DM and glucose metabolism indicators. Finally, GO functional annotation and KEGG pathway enrichment analysis were conducted on the predicted target genes of miR-372-3p. Results: In the discovery set, 32 known miRNAs were detected to have upregulated expression, among which the log₂Fold Change of miR-372-3p was 8.363. In the validation set, the relative expression level of plasma exosomal miR-372-3p of the T2DM group was higher than that of the control group (7.59 vs. 7.00, P=0.028). Furthermore, plasma exosomal miR-372-3p level was negatively associated with fasting insulin (FINS) (r₂ =-0.217, P=0.017) level and pancreatic β-cell function index [Homeostatic model assessment of β-cell function (HOMA-β), r₂ =-0.242, P=0.008] level. After adjusting for relevant confounding factors, each 1-unit increase in the relative expression level of plasma exosomal miR-372-3p was associated with a 38.3% (OR=1.383, 95%CI: 1.008-1.898) increase in the risk of T2DM, a decrease of 2.287 (β=-2.287, 95%CI: -4.164 - -0.410) in FINS level, and a decrease of 13.263 (β=-13.263, 95%CI: -22.972 - -3.554) in HOMA-β level. Bioinformatics analysis suggests that plasma exosomal miR-372-3p may play a role in the pathogenesis of T2DM by modulating the PI3K-Akt and MAPK signaling pathways. Conclusion: The expression levels of plasma exosomal miRNAs of T2DM patients change, and the level of miR-372-3p is positively associated with T2DM.