Community Type 2 Diabetes Subclinical Atherosclerosis Metabolomics Research Based On Bioinformatics

Objective:The "Preventive treatment of diseases" idea of Traditional Chinese medicine advocates early detection and treatment of disease,early prevention and diagnosis is extremely important.Subclinical atherosclerosis in type 2 diabetes is in a subclinical state,which will eventually involve the large artery vascular disease and do great harm to people in the long run.This study using the metabonomics method to find the potential biomarkers of subclinical atherosclerosis in type 2 diabetes from a large number of small molecule metabolites,compare the metabolic level differences of subclinical atherosclerosis in type 2 diabetes and healthy people or vascular disease patients in type 2 diabetes,screen the biomarkers and explore the possible mechanism of disease;mining genes associated with subclinical atherosclerosis in type 2 diabetes based on Bioinformatics,which aims to provide support for early diagnosis and treatment.Methods:A large number of metabolite data were obtained and studied by using 1H-NMR metabolomics,the characteristics of plasma metabolomics were compared among groups through multivariate statistical analysis,and the ROC curve was used to evaluate the potential metabolic markers with diagnostic ability.Based on bioinformatics,GeneCards database was used to search for related genes of subclinical atherosclerotic in type 2 diabetes,Go biological process and KEGG pathway were analyzed by DAVID database and Hub genes were screened by using cytohubba in Cytoscape softwareResults:According to the comprehensive screening of VIP>1 and t test p<0.05,the most important potential metabolites between subclinical atherosclerosis in type 2 diabetes and healthy people are VLDL/LDL?Isoleucine?Leucine?Valine?3-Hydroxybutyrate?Lactate?Proline?Glucose?Taurine?Serine?Glycine?Glutamine?phenylalanine.Among them,VLDL/LDL,Isoleucine,Leucine,Valine,3-Hydroxybutyric acid,Lactate and proline were considered to have potential diagnostic value.The most important potential metabolites between subclinical atherosclerosis in type 2 diabetes and vascular disease patients in type 2 diabetes are VLDL/LDL?Isoleucine?Leucine?Valine?Lactate?Taurine?Glutamine?Glycine.Among them,VLDL/LDL?Isoleucine?Leucine?Valine?Glycine were considered to have potential diagnostic value.Based on bioinformatics,963 genes about subclinical atherosclerosis in type 2 diabetes were found by GeneCards database,the results of Go biological process analysis showed that the changes of the biological process were significantly enriched in inflammatory response,immune response,cell response to lipopolysaccharide,cholesterol homeostasis,etc.KEGG pathyway analysis showed that the enriched pathway mainly related with Cytokine-cytokine receptor interaction,PI3K-akt signaling pathway and HIF-1 signaling pathway;according to the cytohubba plug-in,the hub genes selected were APOE,APOA5,APOB,APP,FBN1,CST3,IL6,APOA1,ALB,CP,among those,APP,ALB and IL6 were the highest degree of enrichment.Conclusions:This study shows that the disorder of glucose metabolism,lipid metabolism and amino acid metabolism may play an important role in the process of turning from healthy people to subclinical atherosclerosis in type 2 diabetes,and then turning into vascular disease patients in type 2 diabetes.Nuclear magnetic resonance analysis showed that there were 13 potential endogenous metabolites in the difference between the subclinical atherosclerosis in type 2 diabetes and the healthy control group,among which VLDL/LDL,Isoleucine,Leucine,Valine,3-Hydroxybutyric acid,Lactate and proline were considered to have potential diagnostic value.There were 8 potential endogenous metabolites in the difference between the vascular disease patients in type 2 diabetes and the subclinical atherosclerosis in type 2 diabetes,among which VLDL/LDL,Isoleucine,Leucine,Valine and Glycine were considered to have some diagnostic value.The 10 hub pathogenic genes related to subclinical atherosclerosis in type 2 diabetes were obtained by bioinformatics,Inflammatory response,cell response to lipopolysaccharide,cholesterol homeostasis,PI3K Akt signaling pathway,HIF-1 signaling pathway and so on may be important pathways in the pathophysiological process of subclinical atherosclerosis in type 2 diabetes.