Identification of differentially expressed plasma small extracellular vesicles miRNAs as biomarkers for type 2 diabetes.

BACKGROUND: The prevalence of Type 2 Diabetes (T2D) has increased over the years. However, the current diagnostic markers such as fasting blood glucose and HbA1c come with certain limitations. Hence, there is a need for a more robust minimally invasive biomarker. This study aimed to identify sets of dysregulated miRNAs in plasma small extracellular vesicles (sEVs) as biomarkers for T2D diagnosis. METHODS: This study was part of the Rice Intervention for Chronic Health (RICH) trial. Plasma sEVs were isolated from T2D and control subjects and characterized. The sEVs-miRNAs expressions were compared using next generation sequencing and validated using digital PCR. Bioinformatic analyses were performed to study the roles of dysregulated miRNAs. Plasma proteins were profiled to study the systemically dysregulated T2D pathways. RESULTS: The levels of miR-142-3p and miR-454-3p were increased in plasma sEVs of T2D subjects. Among a subgroup of T2D subjects in whom glycemic control improved (n = 13), these two upregulated miRNAs also decreased. The combination of sEVs-miR-142-3p, waist circumference, and BMI demonstrated high diagnostic values (AUC-ROC=0.985, p < 0.001) to distinguish between T2D and control subjects. The integrated results from miRNA bioinformatics analysis and plasma proteomics profiling suggested association between the predicted targets of miRNA and systemic dysregulated pathways in T2D. CONCLUSION: This study identified the potential of sEV-miR-142-3p as biomarkers for T2D diagnosis when used in combination with waist circumference and BMI. This study provided preliminary evidence of sEVs-miRNAs in future clinical use for T2D management.