Objective To investigate the relationships of serum levels of G protein-coupled estrogen receptor-1 (GPER1) and interleukin-38 (IL-38) with pregnancy outcomes in patients with gestational diabetes mellitus (GDM).

Methods A total of 120 patients with GDM (GDM group) and 103 pregnant women with normal glucose tolerance (control group) were enrolled between January 2022 and June 2024. Serum GPER1, IL-38, and glycometabolic and lipometric indicators were measured at 24 to 28 weeks of gestation. Pearson correlation analysis was used to assess the correlations of GPER1 and IL-38 with glucolipid indicators. Pregnancy outcomes of GDM patients were recorded. Factors influencing adverse pregnancy outcomes in GDM patients and the predictive value of GPER1 and IL-38 for adverse pregnancy outcomes were analyzed.

Results The serum levels of GPER1 and IL-38 in the GDM group were significantly lower than those in the control group (P < 0.05). Moreover, GPER1 and IL-38 were negatively correlated with glucolipid indicators (P < 0.05). High HOMA-IR and excessive gestational weight gain were identified as risk factors for adverse pregnancy outcomes in GDM patients, while high GPER1 and high IL-38 were protective factors (P < 0.05). The areas under the receiver operating characteristic (ROC) curves for predicting adverse pregnancy outcomes in GDM patients were 0.780 for GPER1 and 0.789 for IL-38, respectively. The area under the ROC curve for the combined prediction of GPER1 and IL-38 was 0.887. The predictive value of the combined GPER1 and IL-38 was higher than that of GPER1 or IL-38 alone (P < 0.05).

Conclusion Reduced serum levels of GPER1 and IL-38 in GDM patients are associated with glycometabolic and lipometric disorders, insulin resistance, and adverse pregnancy outcomes. GPER1 combined with IL-38 exhibits high value in predicting pregnancy outcomes in GDM patients.