Circulating miRNA-195 and miRNA-30c Reflect Metabolic, Inflammatory, and Oxidative Stress Signatures in Diabetic Heart Failure

Diabetic heart failure (DHF) is a complex, progressive condition often viewed as heart failure (HF) with co-morbid diabetes, yet mounting evidence suggests it represents a distinct and more severe clinical entity. This study aimed to characterize differences between HF and DHF and to evaluate the diagnostic and discriminatory utility of circulating miRNA-195 and miRNA-30c and their association with metabolic, inflammatory, and oxidative stress signatures. Glycemic indices, lipid profile, inflammatory and oxidative stress markers, and circulating miRNA-195 and miRNA-30c were assessed in healthy controls and in patients with HF with preserved ejection fraction (HFpEF) without diabetes (HF) and with coexisting type 2 diabetes mellitus (DHF). Correlation analyses were performed between miRNAs and biochemical markers, and the diagnostic utility for discrimination between HF and DHF was evaluated. DHF patients exhibited more severe pathological profile than HF patients. Both HF groups demonstrated atherogenic dyslipidemia; however, DHF showed markedly higher inflammatory activation (NF-κB, TNF-α, IL-6, and CRP) and oxidative stress. miRNA-195 was progressively upregulated from HF to DHF, while miRNA-30c was progressively downregulated. miRNA-195 correlated positively with poor glycemic control, dyslipidemia, inflammation, and oxidative stress, and negatively with antioxidant defenses. miRNA-30c showed the opposite pattern. ROC analysis revealed discriminatory performance of both miRNAs in distinguishing HF from DHF. The coexistence of type 2 diabetes in the studied HFpEF population was associated with more pronounced metabolic, inflammatory, and oxidative stress abnormalities. Circulating miRNA-195 and miRNA-30c showed differential expression and associations with biochemical parameters, suggesting that they may reflect biological alterations accompanying the DHF phenotype. ROC analysis demonstrated exploratory discriminatory performance for both miRNAs in distinguishing HF from DHF, with miRNA-195 showing greater discriminatory performance. These findings provide preliminary evidence supporting further investigation of these miRNAs as potential non-invasive biomarkers in DHF.