Abstract

ObjectivesTo evaluate the influence of genetic variants and clinical characteristics on the risk of gestational diabetes mellitus (GDM) and to construct and verify a prediction model of GDM in early pregnancy.MethodsFour hundred seventy five women with GDM and 487 women without, as a control, were included to construct the prediction model of GDM in early pregnancy. Both groups had complete genotyping results and clinical data. They were randomly divided into a trial cohort (70%) and a test cohort (30%). Then, the model validation cohort, including 985 pregnant women, was used for the external validation of the GDM early pregnancy prediction model.ResultsWe found maternal age, gravidity, parity, BMI and family history of diabetes were significantly associated with GDM (OR > 1; P < 0.001), and assisted reproduction was a critical risk factor for GDM (OR = 1.553, P = 0.055). MTNR1B rs10830963, C2CD4A/B rs1436953 and rs7172432, CMIP rs16955379 were significantly correlated with the incidence of GDM (AOR > 1, P < 0.05). Therefore, these four genetic susceptible single nucleotide polymorphisms (SNPs) and six clinical characteristics were included in the construction of the GDM early pregnancy prediction model. In the trial cohort, a predictive model of GDM in early pregnancy was constructed, in which genetic risk score was independently associated with GDM (AOR = 2.061, P < 0.001) and was the most effective predictor with the exception of family history of diabetes. The ROC-AUC of the prediction model was 0.727 (95% CI 0.690–0.765), and the sensitivity and specificity were 69.9% and 64.0%, respectively. The predictive power was also verified in the test cohort and the validation cohort.ConclusionsBased on the genetic variants and clinical characteristics, this study developed and verified the early pregnancy prediction model of GDM. This model can help screen out the population at high-risk for GDM in early pregnancy, and lifestyle interventions can be performed for them in a timely manner in early pregnancy.

Highlights

  • Gestational diabetes mellitus (GDM) is a common obstetric disease that affects nearly 7% of pregnant women and their offspring [1]

  • Some single nucleotide polymorphisms (SNPs) have been found to be associated with susceptibility to GDM in Asian population [13], such as Korean [14] and Thai [15], but the results remained inconclusive in Chinese population

  • The blood glucose, insulin and HbA1c levels were significantly higher in GDM compared to the controls

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Summary

Introduction

Gestational diabetes mellitus (GDM) is a common obstetric disease that affects nearly 7% of pregnant women and their offspring [1]. Wu et al Diabetology & Metabolic Syndrome (2022) 14:15 of obesity, hyperlipidemia, T2DM, hypertension, brain damage and neuropsychiatric disorders through genetic susceptibility, hyperglycemia, chronic inflammation and other comprehensive factors [6]. For these reasons, early prevention and treatment of GDM is critical for ameliorating both short-term and long-term consequences for mothers and offspring. We intended to find GDM-associated SNPs in Chinese population and hypothesized that an early pregnancy prediction model for GDM can be constructed using genetic risk variants and clinical factors

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