Unveiling the Predictive Model for Macrovascular Complications in Type 2 Diabetes Mellitus: microRNAs Expression, Lipid Profile, and Oxidative Stress Markers Duisenbek, Ayauly Avilés Pérez, María D. Pérez, Miguel Aguilar Benítez, José Miguel Pereira Pérez, Víctor Roger Gorts Ortega, Juan Abdihankyzy, Ussipbek Botagoz Yessenbekova, Arailym López Armas, Gabriela C. Ablaikhanova, Nurzhanyat Olivieri, Fabiola Escames Rosa, Germaine Acuña Castroviejo, Darío Rusanova Rusanova, Iryna type 2 diabetes mellitus cardiovascular disease T2DM macrovascular complications 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. 2024-11-19T08:19:54Z 2024-11-19T08:19:54Z 2024-11-01 journal article Duisenbek, A. et. al. Int. J. Mol. Sci. 2024, 25, 11763. [https://doi.org/10.3390/ijms252111763] https://hdl.handle.net/10481/97058 10.3390/ijms252111763 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI