Risk factors of high-risk foot of diabetes based on differential expression of serum mirnas
Objective To systematically assess miRNAs expression patterns in serum samples from patients with diabetes mellitus(T2D)and T2D high-risk foot patients as well as non-diabetic patients.Methods A total of 92 patients with T2D who were hospitalized in the Endocrinology Department of Hebei Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from June 2021 to June 2022 were collected.Of these 92 participants,46 were diagnosed with high-risk foot but no foot ulcers and were includ-ed in the T2D high-risk foot group;the remaining patients were in-cluded in the T2D group.Forty-six healthy individuals with normal glucose tolerance who underwent physical examination at our hospital were selected as normal controls.Blood samples were collected from all participants,and RT-qPCRbased miRNA profiles of TLDA microarray serum samples were used,and the differentially expressed miRNAs in them were verified by RT-qPCR.Results TLDA analysis showed that of the 754 miRNAs evaluated,25 were upregulat-ed and 118 were downregulated in both T2D patients compared to controls.RT-qPCR validation showed that compared to controls,the levels of four miRNAs,including miR-23,miR-195-5p,miR-205-5p,and miR-203,in the T2D group and T2D high-risk foot group were significantly increased(P<0.05).In addition,the levels of the above four serum miRNAs were higher in patients in the T2D high-risk foot group than the T2D group(P<0.05).In multivariate analysis,only miR-195-5p(OR=6.9,95%CI,2.0-24.2,P= 0.003)and miR-205-5p(OR=7.2,95%CI,1.6-32.0,P=0.009)were independently associated with T2D alone when using the control group as the reference category,and miR-195-5p(OR= 6.9,95%CI,2.0-24.2,P<0.001),and miR-205-5p(OR=11.0,95%CI,2.8-43.2,P=0.001)were independently associated with T2D high-risk foot.When the T2D group was used as the refer-ence category,only miR-195-5p(OR=3.0,95%CI,1.6-5.7,P=0.001)and miR-205-5p(OR=2.3,95%CI,1.2-4.2,P= 0.012)were independently associated with T2D high-risk foot.miR-195-5p and miR-205-5p were significantly associated with T2D high-risk foot when area under the ROC curve(AUC)were 0.74 and 0.70 when differentiating the T2D group from the control group,0.87 and 0.84 when differentiating the T2D high-risk foot group from the control group,and 0.65 and 0.62 when differentiating the T2D group from the T2D high-risk foot group.Conclusion miR-195-5p and miR-205-5p may become novel risk indicators for T2D and high-risk foot and may play an important role in the pathogenesis and progression of T2D and high-risk foot.