Dysregulated miRNA-375, IL-17, TGF-ß, and Microminerals Are Associated with Calpain-10 SNP 19 in Diabetic Patients: Correlation with Diabetic Nephropathy Stages.

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-ß and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-ß, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-ß, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-ß, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-ß, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-ß, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Non-classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease.

AIMS/INTRODUCTION: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD. MATERIALS AND METHODS: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay. RESULTS: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence. CONCLUSIONS: Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.