Integrated miR-34a/SIRT1 Axis Links Inflammation, Oxidative Stress, and Endothelial Dysfunction to Cardiovascular Risk in Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a major driver of cardiovascular disease (CVD), yet current risk stratification tools fail to capture underlying molecular dysregulation. This study aimed to characterize an integrated molecular signature associated with cardiovascular risk in T2DM. A total of 128 individuals (96 T2DM and 32 controls) were evaluated. Circulating miR-34a expression was quantified by RT–qPCR, and protein biomarkers including SIRT1, inflammatory markers (IL-6, TNF-α, hs-CRP), oxidative stress markers (MDA, total antioxidant capacity), and endothelial dysfunction markers (VCAM-1, ICAM-1) were measured by ELISA. Cardiovascular risk was assessed using the Framingham Risk Score. miR-34a expression was significantly elevated in T2DM, particularly in individuals with high cardiovascular risk (p < 0.001). This was accompanied by reduced SIRT1 levels and a progressive increase in inflammatory, oxidative, and endothelial dysfunction markers. Integrated analysis revealed strong correlations between miR-34a upregulation, SIRT1 suppression, and systemic pathophysiological alterations. Multivariate regression identified miR-34a, SIRT1, IL-6, and MDA as independent predictors of high cardiovascular risk. A combined biomarker model demonstrated excellent discriminative performance (AUC = 0.92), outperforming individual markers. These findings support the existence of a coordinated miR-34a/SIRT1-driven molecular axis linking inflammation, oxidative stress, and endothelial dysfunction to cardiovascular risk in T2DM. This integrated biomarker approach may improve risk stratification and support precision cardiometabolic medicine.