Unveiling the Predictive Model for Macrovascular Complications in Type 2 Diabetes Mellitus: microRNAs Expression, Lipid Profile, and Oxidative Stress Markers

Abstract

To assay new circulating markers related to macrovascular complications (MVC) in type 2 diabetes mellitus (T2DM), we carried out a descriptive cross-sectional study. We recruited 30 controls (CG), 34 patients with T2DM (DG), and 28 patients with T2DM and vascular complications (DG+C); among them, 22 presented MVC. Peripheral blood was used to determine redox status (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; glucose-6- phosphate dehydrogenase, G6PD) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid peroxidation, LPO), nitrite levels in plasma (NOx). Inflammatory markers (IL-1β, IL-6, IL-10, IL-18, MCP-1, TNF-α) and the relative expression of c-miRNAs were analyzed. The real-time PCR results showed that the expressions of miR-155-5p, miR-21-5p, miR-146a-3p, and miR- 210-3p were significantly higher in the DG group compared to the CG. The DG+C group presented statistically relevant differences with CG for four miRs: the increased expression of miR-484-5p, miR-21-5p, and miR-210-3p, and decreased expression of miR-126a-3p. Moreover, miR-126a-3p was significantly less expressed in DG+C compared to DG. The application of binary logistic regression analysis and construction of receiving operator characteristic curves (ROC) revealed two models with high predictive values for vascular complications presence: (1) HbAc1, creatinine, total cholesterol (TC), LPO, GPx, SOD, miR-126, miR-484 (Exp(B) = 0.926, chi2 = 34.093, p < 0.001; AUC = 0.913). (2) HbAc1, creatinine, TC, IL-6, LPO, miR-126, miR-484 (Exp(B) = 0.958, Chi2 = 33.863, p < 0.001; AUC = 0.938). Moreover, our data demonstrated that gender, TC, GPx, CAT, and miR-484 were associated with MVC and exhibited higher predictive values (Exp(B) = 0.528, p = 0.024, Chi2 = 28.214, AUC = 0.904) than classical variables (Exp(B) 0.462, p = 0.007, Chi2 = 18.814, AUC = 0.850). miR-126, miR-484, IL-6, SOD, CAT, and GPx participate in vascular damage development in the studied diabetic population and should be considered for future studies.