Circulating microRNA signatures differentiate type 2 diabetes and predict myocardial infarction severity: bench to bedside analysis

This study investigates selected miRNAs identified from the literature and characterized through bioinformatic analysis, assessing their differential expression in myocardial infarction patients with and without diabetes to elucidate the role of non-coding RNAs in disease severity and prognosis. 106 patients with available baseline and 26-week plasma samples were included in the analysis of 212 longitudinal samples, with RNA analyses conducted. MiRNA expression quantified via qPCR, and analyzed with statistical methods including ROC and multivariate logistic regression, to evaluate miRNAs as biomarker. At admission, miR-210-5p expression was significantly lower in T2D patients (p < 0.0001), while miR-195-5p was significantly higher (p = 0.001). ROC analysis demonstrated diagnostic utility for T2D, with an AUC of 0.811 for miR-210-5p and 0.723 for miR-195-5p. Over 26 weeks, miR-210 increased in both groups but remained consistently lower in T2D, whereas miR-21 significantly decreased in both groups (p < 0.0001). Severe AMI (LVEF ≤ 40%) was observed in 22 patients (21%). Baseline miR-1-5p expression was significantly higher in severe AMI (p = 0.001) and demonstrated stronger discriminative ability (AUC 0.765) than eGFR (AUC 0.669) or NT-proBNP (AUC 0.647), whereas hsTroponin was not associated with severity. A combined panel of high miR-1-5p, low eGFR, and high NT-proBNP significantly improved discrimination for severe AMI (AUC 0.823; 95% CI 0.71–0.94; p = 0.00004). In multivariable analysis, this panel independently predicted LVEF ≤ 40% (OR 8.04; 95% CI 2.21–29.27; p = 0.002). MiR-210, miR-21, and miR-1-5p, showed a significant role in understanding the pathophysiology of AMI and its association with diabetes status and AMI severity. A combined miRNA-clinical biomarker panel (such as miR-1-5p, eGFR, and NT-proBNP) improves risk stratification beyond single parameters. Although mechanistic validation is warranted, these findings support the translational potential of miRNAs as precision biomarkers in cardiometabolic cardiovascular disease. The study was approved by the relevant regulatory authorities, by the Ethics Committee of the Medical University of Graz, Austria (EK 29–179 ex 16/17; EudraCT 2016-004591-22) and registered on ClinicalTrials.gov (NCT03087773) 14/March/2017. https://clinicaltrials.gov/study/NCT03087773