Circulating miRNAs as a predictive biomarkers of progression from prediabetes to diabetes: outcomes of 5-year prospective observational study

The aim of this study was to conduct a baseline comparison of serum-circulating miRNA in prediabetic individuals with the distinction between those who later progressed to type 2 diabetes (T2DM) and those who did not. The expression level of 798 miRNAs using NanoString technology was examined. Spearman correlation, ROC curve analysis, and logistic regression modeling were performed. Gene ontology (GO), canonical pathways analysis were used to explore the biological functions of the miRNA target genes. The study revealed that 18 miRNAs were upregulated in serum samples of patients who later progressed to T2DM. Pathway analysis showed that miRNA target genes were mainly significantly enriched in neuroinflammation signaling, Myc mediated apoptosis signaling and tumoricidal function of hepatic natural killer (NK) cells. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (AUC=97.1%; 90.2%; 88.7%; respectively). Validation by qRT-PCR confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients. 30 serum samples of prediabetes patiensts were included. T2DM grop patients developed diabetes after 5 years from baseline visit. Control groupdid not develop T2DM.