| Background: Type 2 diabetes mellitus(T2DM)is a progressive multifactorial metabolic disorder.Long-term poor control of blood glucose in patients with T2 DM can lead to a variety of concurrent diseases.Coronary heart disease is the most common complication of diabetes.It is also the main cause of mortality in diabetic patients,but there is currently no effective molecular marker for T2DM-related coronary heart disease risk prediction and diagnosis.MicroRNAs(miRNAs)regulate gene expression by inhibiting and/or reducing the stability of their target messenger RNA at the post-transcriptional level,and miRNAs are involved in numerous biological and physiological processes.It plays an important role in the development of T2 DM,insulin production and secretion,insulin resistance and diabetic complications.The study of serum miRNAs in patients with type 2 diabetes mellitus complicated with coronary atherosclerosis will have potential applications in the prevention,early diagnosis and treatment of T2 DM with coronary atherosclerosis.Objective:This study intends to search for miRNAs closely related to T2 DM and coronary atherosclerosis by literature search,and then the primary miRNAs were screened and verified one by one in two stages using real-time fluorescent quantitative PCR(RT-qPCR)among batch healthy control group,T2 DM group,T2 DM combined with coronary atherosclerosis group and coronary atherosclerosis group.To analyze the expression of related miRNAs in the serum of T2 DM patients with coronary atherosclerosis,and to find serum miRNAs that can be used as potential biomarkers for T2 DM with coronary atherosclerosis and evaluate their clinical value.Methods:Through literature search and reading,miR-126,miR-107,miR-326,miR-29 a and miR-10 a,which are closely related to T2 DM and coronary atherosclerosis,were selected as potential miRNAs for T2 DM combined with coronary atherosclerosis.The subjects were divided into four groups: healthy control group,T2 DM group,T2 DM combined with coronary atherosclerosis group and coronary atherosclerosis group.In the rescreening stage,128 cases(32 cases in each group)were subjected to serum RNA extraction,tailing and reverse transcription,real-time quantitative PCR analysis,and cel-miR-39-3p was used as externalreference.For the serum miRNAs showing significant differences between the groups during the rescreening stage,Increased number of specimens,and the results of the rescreening were verified in 176 cases(44 cases in each group).Finally,a variety of statistical methods were used to systematically analyze and evaluate.The clinical value of specific changes in serum miRNAs as T2DM-associated coronary heart disease biomarkers.Results: The results of RT-qPCR screening showed that the expression levels of serum miR-126 and miR-10 a in T2 DM,T2DM combined with coronary atherosclerosis group and coronary atherosclerosis group were significantly decreased(P<0.05),serum miR-107,miR-326 and miR-29 a expression levels increased significantly(P <0.05).There was no significant difference in miR-126 between T2 DM group and coronary atherosclerosis group(P>0.05);There was no significant difference in the expression level of miR-107,miR-326 and miR-29 a in T2 DM group and T2 DM combined with coronary atherosclerosis group(P>0.05).The difference of miR-10 a between the groups was significant(P<0.01),and the expression of the atherosclerosis group was the most obvious.The results of RT-qPCR showed that the expression differences of miR-126 and miR-10 a in each group were consistent with the results of the first experiment.The results of multivariate correlation analysis showed that miR-126 associated with miR-10 a,fasting blood glucose(FBG)and HCY significantly;miR-10 a was significantly associated with miR-126,T-CH,and HCY.Diagnostic evaluation results: the area under the diagnostic ROC curve of miR-126,miR-10 a differentiated T2 DM with coronary atherosclerosis group and healthy control group,and differentiated T2 DM with coronaryatherosclerosis group and T2 DM group were: 0.973,0.880(P < 0.01)and 0.954,0.857(P < 0.01).Conclusion: Serum miRNA-126,miRNA-107,miRNA-326,miRNA-29 a and miRNA-10 a may be involved in the development of T2 DM and T2 DM combined with coronary atherosclerosis.miRNA-126 and miRNA-10 a are expected to become a potential biomarker for T2 DM combined with coronary atherosclerosis disease. |
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