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

Duisenbek A. Avilés Pérez M.D. Pérez M. Aguilar Benitez J.M. Pereira Pérez V.R. Gorts Ortega J. Ussipbek B. Yessenbekova A. López-Armas G.C. Ablaikhanova N. Olivieri F. Escames G. Acuña-Castroviejo D. Rusanova I.
November 2024 Multidisciplinary Digital Publishing Institute (MDPI)

International Journal of Molecular Sciences
2024 #25 Issue 21

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.

cardiovascular disease , inflammation , microRNA , oxidative stress , T2DM macrovascular complications , type 2 diabetes mellitus

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Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Al-Farabi Av. 71, Almaty, 050040, Kazakhstan
Endocrinology and Nutrition Unit, Instituto de Investigación Biosanitaria de Granada Ibs.GRANADA, University Hospital San Cecilio, Granada, 18007, Spain
Hospital Alto Guadalquivir, Andujar, 23740, Spain
Hospital de Alta Resolución de Alcalá la Real, Alcalá de Real, 23680, Spain
Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Granada, 18071, Spain
Departamento de Investigación y Extensión, Centro de Enseñanza Técnica Industrial, C. Nueva Escocia 1885, Guadalajara, C.P. 44638, Mexico
Department of Clinical and Molecular Sciences, Disclimo, Università Politecnica delle Marche, Ancona, 60126, Italy
Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, 60121, Italy
Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, 28029, Spain
Instituto de Investigación Biosanitaria ibs. GRANADA, Hospital Universitario San Cecilio, Granada, 18016, Spain
Centro de Investigación Biomédica, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, 18016, Spain
Department of Physiology, Faculty of Medicine, University of Granada, Granada, 18016, Spain

Department of Biophysics
Endocrinology and Nutrition Unit
Hospital Alto Guadalquivir
Hospital de Alta Resolución de Alcalá la Real
Department of Biochemistry and Molecular Biology I
Departamento de Investigación y Extensión
Department of Clinical and Molecular Sciences
Advanced Technology Center for Aging Research
Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES)
Instituto de Investigación Biosanitaria ibs. GRANADA
Centro de Investigación Biomédica
Department of Physiology

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