Establishment Of Risk Prediction Model And Screening Of Risk Genes For Gestational Diabetes Mellitus

Gestational diabetes mellitus(GDM)is one of the most common obstetric complications during pregnancy.GDM can lead to a variety of adverse maternal and infant outcomes during the perinatal period.Including gestational hypertension.polyhydramnios.abortion,premature delivery,macrosomia.fetal intrauterine growth restriction,abnormal embryonic development and even fetal death.Studies have found that pregnant women with GDM often have a variety of other medical complications,and the risk factors of GDM are complex and regional,and previous studies are not universal.In addition to related clinical indicators.GDM pregnant women often have changes in a variety of metabolism-related genes,including genes related to glucose metabolism.lipid metabolism and insulin resistance.Therefore,to further understand the prevalence of GDM in Suzhou area,analyze the local risk factors of GDM,and screen the related risk genes,so as to provide a new theoretical basis and basis for the clinical management,prediction and prevention of GDM in this region.Part Ⅰ Establishment of risk prediction model for gestational diabetes mellitusObjective:The prevalence of GDM among pregnant women in the First Affiliated Hospital of Suzhou University was counted,the high-risk factors of GDM among pregnant women were analyzed to construct a GDM prediction model.Methods:1.The number of pregnant women who give birth each year were collected in the First Affiliated Hospital of Suzhou University from January 2020 to December 2022,and the number of pregnant women with GDM were counted at the same time.According to the statistical results above.we calculated the annual prevalence rate of GDM.2.analyzed the trend of the prevalence rate.427 GDM pregnant women undergoing obstetric examination and delivery with complete medical records were retrospectively collected in the First Affiliated Hospital of Suzhou University from January 2019 to June 2020,and 519 non-GDM pregnant women during the same period were selected as the control group.Clinical information of above two groups were collected,including age,gestational weeks,gestational frequency,birth frequency,number of miscarriages,body mass index(BMI)before pregnancy,weight gain during pregnancy,mode of conception,number of fetuses,pregnancy complications including thyroid dysfunction,hypertension,and anemia,etc.,past history including family history of diabetes,history of GDM,history of polycystic ovary syndrome(PCOS),history of chronic hypertension,and history of pregnancy with hypertension,mode of delivery,amount of bleeding within 24 h after delivery,blood transfusion during hospitalization,whether there is birth canal injury,whether to transfer to an intensive care unit,whether to undergo hysterectomy,whether there is maternal death,newborn birth weight.Apgar scores at 1 min and 5 min of birth,and neonatal bleeding symptoms.The risk factors of GDM were analyzed byt-test.χ2 and Logistic regression analysis,and a multivariate logistic regression model was established.Results and conclusions:1.During the three years from 2020 to 2022,the total annual prevalence of GDM among pregnant women in tthe First Affiliated Hospital of Suzhou University was 13.38%.14.68%.and 1 6.02%.respectively,which indicated that The prevalence of GDM in Suzhou has increased year by year in recent three years.2.Older age(>35 years old),pre-pregnancy BMI(>24 kg/cm2).and excessive weight gain during pregnancy(>12.5 kg)were independent risk factors for GDM.The area under the ROC curve of the prediction model is 0.841.P<0.001.and the 95%confidence interval is 0.817-0.862.Besides,the sensitivity of clinical prediction was 80.71%.and the specificity was 76.67%,indicating that the multivariate logistic regression model had certain predictive value for GDM.Part Ⅱ Screening of risk genes for gestational diabetes mellitus based on transcriptome sequencingObjective:Based on transcriptome sequencing,differentially expressed genes in the whole blood of pregnant women with GDM and non-GDM were screened and validated in populations with different clinical characteristics.Methods:1.The whole blood samples from GDM(N=5)and non-GDM pregnant women(N=5)who were pregnant for 24-28 weeks were collected during the period from June 2020 to July 2020.The differential genes with the whole blood samples were detected via high-throughput transcriptome sequencing Illumina HiSeq.2.The whole blood samples from GDM(N=55)and non-GDM pregnant women(N=15)who were pregnant for 24-28 weeks were collected during the period from July 2020 to December 2020.The expression changes of TUBB2A gene with high expression levels and significant differences in whole blood samples were detected using RT-qPCR.and the changes in clinical outcomes within 2 years after delivery were followed up.Results:1.A total of 16488 genes were expressed in the sequenced samples.Compared to the non-GDM group.34 genes were significantly upregulated and 50 genes were significantly downregulated in the GDM group.Among them,the five genes SLC7A11,RERN,TUBB2A,KRT1,and CA1 had high expression levels and significant differential expressions,which were consistent with the RT-qPCR verification results.2.Compared with non-GDM pregnant women,the TUBB2A mRNA levels in the whole blood samples of GDM pregnant women at 24-28 weeks of gestation was significantly decreased(P<0.01).During the follow-up.it was found that within two years after delivery,the pregnant women in the non-GDM group had no metabolic abnormalities with clinical symptoms,whereas 10 pregnant women in the GDM group had continued abnormal glucose metabolism(2 of them had GDM again.5 had impaired fasting glucose,and 3 were diagnosed with type 2 diabetes).The GDM group was divided into two groups based on whether there were persistent glucose metabolism abnormalities after delivery.The results showed that the expression levels of TUBB2A mRNA in pregnant women with persistent glucose metabolism abnormalities after delivery was significantly lower than that in pregnant women without such abnormalities(P<0.01).Conclusion:There are significant differences in the transcriptome of whole blood samples from GDM and non-GDM pregnant women at 24-28 weeks of gestation,and the differentially expressed genes including SLC7A11,RERN,TUBB2A,KRT1,and CA1 may be related to the process of GDM.The expression level of TUBB2A gene was negatively correlated with persistent glucose metabolism abnormalities in GDM and GDM pregnant women,indicating that TUBB2A gene may serve as a protective factor for GDM.and has certain clinical value and significance for the diagnosis and prognosis evaluation of GDM.