| ObjectiveIn this study,the UPLC/Q-TOF MS-based metabolomics method was used to analyze the serum profiles of diabetics,impaired glucose regulation and normal glucose tolerance populations.Screening and identification of serum metabolic markers in impaired glucose regulation populations were conducted to explore mechanism of occurrence and development impaired glucose regulation,which would provide a theoretical basis for the early diagnosis and intervention of the impaired glucose regulation.MethodsCollection and screening of metabolic markers:(1)Collecting 50 serum samples of diabetic patients,30 serum samples of the impaired glucose regulation,and 50 serum samples of normal glucose tolerance subjects.(2)After the sample was pretreated,the metabolomic profiles of the three groups were detected using the metabolomics method of UPLC/Q-TOF MS.(3)Multidimensional statistical analysis including principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA)and orthogonal partial least squares discriminant analysis(OPLS-DA)are used to analyze the clustering of metabolites.Differential metabolites were obtained and were selected as metabolic markers using VIP>1.0,P<0.05 and other conditions as a filter.Identification and analysis of metabolic markers:(1)Using criteria such as tolerances of less than 5 ppm as matching conditions,the information obtained from experiment was used to match metabolite information in the HMDB,Metlin and Chemspider databases to identify selected metabolic markers.Metabolomic pathway analysis of these markers was performed by MetaboAnalyst platform to explore metabolic pathways that change during the development of impaired glucose regulation.Results1.Eight differential metabolites were identified after PCA and OPLS-DA analysis among serum metabolic profiles in Diabetes,Impaired Glucose Regulation and Normal Glucose Tolerance Groups: behenamide,cholesterol acetate,DHA,hexahexyl oleate,inosine,methyltestosterone,L-Phenylalanine and(2R,6x)-7-Methyl-3-methylene-1,2,6,7-octanetriol 2-glucoside.2.Seven differential metabolites were identified in serum metabolic profiles after PLS-DA analysis between impaired glucose regulation and normal glucose tolerance Groups: Behenamide,Cholesteryl Acetate,DHA,Hexahexyl oleate,methyltestosterone and(halo)-phenylalanine and(2R,6x)-7-methyl-3-methylene-1,2,6,7-octanetriol 2-Glucoside.With the exception of cholesterol acetate,all other metabolic markers were performed higher level in serums of impaired glucose regulation group.3.Ten differential metabolites were identified in serum metabolic profiles after PLS-DA analysis between impaired glucose regulation and normal glucose tolerance Groups: L-phenylalanine,L-tryptophan,inosine,alpha-fertility(2R,6x)-7-Methyl-3-methylene-1,2,6,7-octanetriol 2-glucoside,hexanoctyl oleate,cholesterol acetate,EPA,DHA and 11-oxohexadecanoic acid.Among them,the top five metabolic markers increased during the development of impaired glucose regulation and the latter five decreased during this process.4.Metabolic markers obtained from the metabolic profile analysis of each group were summarized and a total of 13 non-repetitive metabolic markers associated with impaired glucose regulation were found.There were three specific metabolic markers between impaired glucose regulation group and normal glucose tolerance group: docosamide,(halo)-phenylalanine and methyltestosterone.There are six specific metabolic markers among impaired glucose regulation group and diabetes groups: Lphenylalanine,alpha-fertoxidase,L-tryptophan,inosine,EPA and 11-oxo On behalf of hexadecane.5.Metabolism pathway analysis of the selected 13 Metabolic markers revealed that the pathway of sphingolipid metabolism and phenylalanine,tyrosine and tryptophan biosynthesis and were significantly altered during the development of impaired glucose regulation.Conclusion1.It is verified that UPLC/Q-TOF MS-based metabolomics methods can be used to discover the feasibility of metabolic markers with impaired glucose regulation.2.Behenylamide,(halo)-phenylalanine and methyltestosterone have potential impairments in the diagnosis for impaired glucose regulation.3.Six compounds including L-Phenylalanine,alpha-tocopherol,L-tryptophan,inosine,EPA and 11-oxohexadecane can be used as early warning for development from impaired glucose regulation to diabetes.4.Phenylalanine,tyrosine and tryptophan biosynthetic pathways and sphingolipid metabolic pathways have been upregulated in people with impaired glucose regulation... |
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