Analysis of Circulating MicroRNAs in Patients with Diabetic Foot Ulcers and Lower Limb Amputation

Non-healing diabetic foot ulcers substantially increase the risk of infection and lower limb amputation, contributing to elevated morbidity and mortality among individuals with diabetes. MicroRNAs (miRNAs) have been widely studied as potential early biomarkers for various diseases. This pilot study assessed circulating miRNA expression profiles in adults with diabetic ulcers (n = 31), individuals who underwent limb amputation due to foot ulcers (n = 20), and 50 control subjects using RT-qPCR. Patients with diabetic foot ulcers and amputations exhibited significantly higher plasma levels of miR-7e, miR-17, miR-33, and miR-191 compared to controls (p < 0.05). Notably, miR-191 expression was significantly greater in patients with limb amputations than in those with diabetic ulcers (p = 0.001). A strong positive correlation was identified between miR-191 and glucose levels (r = 0.682, p = 0.001), while an inverse correlation was observed with HDL-C (r = -0.476, p = 0.034). Let-7e also correlated positively with glucose (r = 0.543, p = 0.013) and negatively with HDL-C (r = -0.491, p = 0.028). Significant associations were found between miR-17-5p and both cholesterol (r = 0.584, p = 0.007) and LDL-C (r = 0.495, p = 0.026). ROC analyses supported the diagnostic value of these miRNAs: miR-17 and miR-191 achieved AUCs of 0.742 (p = 0.000) and 0.671 (p = 0.006), respectively, indicating their potential as biomarkers for disease identification. These findings suggest that increased expression of let-7e, miR-17, and miR-191 may serve as significant biomarkers.