<strong>METABOLIC MEMORY IN DIABETIC FOOT SYNDROME (DFS): MICRO-RNAs, SINGLE NUCLEOTIDE POLYMORPHISMS (SNPs) FREQUENCY AND THEIR RELATIONSHIP WITH INDICES OF ENDOTHELIAL FUNCTION AND ADIPO-INFLAMMATORY DYSFUNCTION.</strong> Item

The aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers. We examined the effects of epigenetic changes on miRNA 126, 305, and 217 expression and the frequency of the SNPs of genes encoding inflammatory molecules (e.g., IL-6 and TNF-alpha[Ed1] [AT2] ) and their correlations with serum levels of proangiogenic molecules (e.g., ENOS, VEGF and HIF-1alpha) and several adipokines as well as with endothelial dysfunction, assessed noninvasively by reactive hyperaemia peripheral artery tonometry . Between March 2021 and June 2022, 110 patients were enrolled into the study: 50 diabetic patients with diabetic foot injuries, 40 diabetic patients without ulcerative complications and 20 nondiabetic patients as the control group. Results: Diabetic subjects with lower limb ulcerative lesions exhibited higher levels of inflammatory cytokines, such as VEGF (191.40±200 pg/mL vs. 98.27±56.92 pg/mL vs. 71.01±52.96 pg/mL; p=0.22), HIF-1alpha (40.18±10.80 ng/mL vs. 33.50±6.16 ng/mL vs. 33.85±6.84 ng/mL; p=0.10[Ed3] [AT4] ), and Gremlin-1 (1.72±0.512 ng/mL vs. 1.31±0.21 ng/mL vs. 1.11±0.19 ng/mL; p< 0.0005), than those without lower limb ulcers and healthy controls. Furthermore, we observed that miR-217-5p and miR-503-5p were 2.19-fold (p<0.05) and 6.21-fold (p=0.001) more highly expressed in diabetic foot patients than in healthy controls, respectively. Additionally, diabetic patients without lower limb ulcerative complications showed 2.41-fold (p=0) and 2.24-fold (p=0.029) higher expression of miR-217-5p and miR-503-5p, respectively, than healthy controls. Finally, diabetic patients with and without ulcerative complications of the lower limbs showed higher expression of the VEGFC2578A CC polymorphism (p=0.001) and lower expression of the VEGFC2578A AC polymorphism (p<0.005) than the healthy control population. We observed a significant increase in Gremlin-1 levels[Ed5] in patients with diabetic foot, suggesting that this inflammatory adipokine may serve as a predictive marker for the diagnosis of diabetic foot. [