| Background : Gestational diabetes mellitus(GDM)refers to the abnormal glucose tolerance associated with pregnancy,which causes irreversible damage to the health of mothers and children.The long-term risk of type 2 diabetes was significantly increased in GDM patients,and the incidence of neuropsychiatric diseases in offspring was increased.At present,the drugs used to treat GDM have some side effects,and the diagnosis of blood glucose is not perfect.The best strategy to prevent and treat GDM is to use biomarkers to diagnose and intervene when GDM initially produces metabolic disorder.Metabonomics has become a hot topic to study the mechanism of GDM's threat to maternal and children's health.It can be used to elucidate the metabolic disorder of GDM,and the differential metabolites between GDM and normal pregnant women can be found as biomarkers of GDM for treatment.In addition,due to the long pregnancy cycle,the metabolic disorder of pregnant women is also constantly changing.Therefore,GDM biomarkers should have a long-term and effective feature with pregnancy.In this study,metabolic disorder analysis was carried out on the rarely reported pregnancy end-point,and some candidate biomarkers were found,which provided a theoretical basis for mutual confirmation with the existing results of the previous stages,so as to further clarify the metabolic disorder and find the long-term effective biomarkers of GDM.However,there are defects in the previous studies:there are few cases in the group,the conclusions are biased,and the universality is not high;only for a single sample type,the relationship between various metabolic disorders caused by GDM cannot be resolved.By increasing the number of study population and analyzing the metabonomics of blood,urine,feces samples at the end of pregnancy,we try to get a more objective understanding of the metabolic disorder of GDM,and make correlation analysis of the metabonomics data of various samples to preliminarily study the relationship between the metabolicdisorders of different types of GDM samples.Studying and analyzing the end-point metabolism of pregnancy,so as to provide theoretical basis for better understanding of gestational diabetes mellitus.Objective: This study intends to use NMR metabolomics to detect and analyze umbilical cord blood,urine,and fecal metabolism samples of pregnant women with gestational diabetes and normal controls at the endpoint of pregnancy.Combined with integrated metabonomics association analysis technology,to more comprehensively analyze the effect of gestational diabetes on endpoint pregnancy metabolism.Methods: 1.Application of 1H-NMR metabolomics technology with multivariate statistical analysis to analyze the differential metabolites of umbilical cord blood,urine,and feces of pregnant women with gestational diabetes mellitus and normal control samples at the endpoint of pregnancy;2.Using Metabo Analyst(http://www.metaboanalyst.ca)to analyze differential metabolic pathways of differential metabolites between umbilical cord blood,urine,and feces of pregnant women with gestational diabetes mellitus and normal control samples;3.Integrated metabonomics association analysis technology was used to systematically analyze the metabolic changes related to intestinal metabolism and cord blood metabolism at the end of pregnancy.Results: 1.Seven different metabolites of lipids,lysine,glutamic acid,glutamine,methanol,lactic acid and glucose were found between umbilical cord blood of pregnant women with gestational diabetes and pregnancy control samples;D-glutamine and D-glutamate metabolism,arginine biosynthesis,alanine,aspartate and glutamate metabolism are significantly affected by GDM,and these metabolic pathways are all related to glutamic acid and glutamine.2.Twelve different metabolites such as alanine,phenylalanine,glycine,hippurate,3-hydroxybutyric acid,2-hydroxyisobutyrate,citric acid,4-ethylphenol glucuronide,myo-inositol,lactate,acetoin and glucose were found between urine of pregnant women with gestational diabetes andpregnancy control samples;glyoxylate and dicarboxylate metabolism,phenylalanine metabolism,phenylalanine,tyrosine and tryptophan biosynthesis three metabolic pathways are significantly affected by GDM,and these metabolic pathways involve four metabolites: glycine,citric acid,phenylalanine,and hippuric acid.3.Six differential metabolites of N6-acetyllysine,acetoacetate,hypotaurine,4-ethylbenzoic acid,taurine and glucose were found between feces of pregnant women with gestational diabetes and pregnancy control samples;the metabolic pathway of taurine and hypotaurine metabolism are most significantly affected by GDM,and this metabolic pathway is related to the differential metabolites taurine and hypotaurine.4.CIA and PA analysis showed a certain correlation between fetal metabolism and umbilical cord blood metabolism at the end of pregnancy;CCA analysis shows that glutamic acid and N-acetylglycoprotein in intestinal metabolism significantly contribute to changes in the umbilical cord blood metabolome of GDM compared to the control group.Conclusion: 1H-NMR metabolomics analysis of gestational diabetes in three different samples of umbilical cord blood,urine,and feces at the end of pregnancy found that D-glutamine and D-glutamate metabolism,arginine biosynthesis,alanine,aspartate and glutamate metabolism,glyoxylate and dicarboxylate metabolism,phenylalanine metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,taurine and hypotaurine metabolism were significantly affected by GDM.These metabolic pathways involve the variable contents of glutamic acid,glutamine,glycine,citric acid,phenylalanine,hippuric acid,taurine,and hypotaurine.Integrated metabonomics association analysis system showed that glutamic acid and N-acetylglycoprotein in intestinal metabolism at the end of pregnancy significantly contributed to changes in the umbilical cord blood metabolome of GDM compared to the control group.Comprehensive analysis of the impact of gestational diabetes on endpoint pregnancy metabolism,so as to confirm with the metabolism research of early,middle and late gestationaldiabetes,providing the basis for finding the long-term effective biomarker of GDM,preventing gestational diabetes better,exploring the effect of intestinal flora closely related to intestinal metabolism on gestational diabetes. |
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