Abstract:Objective To investigate the relationship between exposure to air pollutants and heavy metals and the risk of gestational diabetes mellitus (GDM), as well as the potential underlying mechanisms, in order to provide scientific evidence for the prevention and treatment of GDM.Methods A nested case-control study design was employed, including 120 pregnant women with GDM from Wuxi People's Hospital between January 2021 and December 2023. Each GDM case was matched 1:1 with a healthy pregnant woman based on age and gestational week at the time of the oral glucose tolerance test. The residential addresses of the participants were collected, and the concentrations of air pollutants (PM2.5, NO2, SO2, CO, etc.) during pregnancy were assessed using air quality monitoring data from the Wuxi Environmental Protection Bureau. Heavy metals such as lead, mercury, and cadmium in the blood of the pregnant women were measured using atomic absorption spectroscopy. Multivariate logistic regression analysis was performed to evaluate the association between exposure to air pollutants and heavy metals and the risk of GDM, and to further explore the potential biological mechanisms.Results No statistically significant differences were found between the study group and control group in terms of registration age, gestational week at registration, height, parity distribution, or maternal education level (P > 0.05). Statistically significant differences were observed between the two groups in BMI at registration, systolic blood pressure, diastolic blood pressure, GCT, fasting plasma glucose, 1-hour postprandial plasma glucose, 2-hour postprandial plasma glucose and family history of diabetes (P < 0.05). Comparisons of PM2.5, PM10, SO2, NO2, CO, lead, cadmium, arsenic and mercury levels between the study group and control group all showed statistically significant differences (P < 0.05), with the study group demonstrating higher levels of these pollutants than the control group. Multivariate logistic regression analysis indicated that elevated levels of PM2.5 [O^R = 1.148 (95% CI:1.005, 1.311) ], PM10 [O^R =1.081 (95% CI: 1.004, 1.165) ], SO2 [O^R =1.357 (95% CI:1.049, 1.756) ], NO2 [O^R =1.107 (95% CI:1.009, 1.216) ], CO [O^R =34.509 (95% CI: 2.207, 539.556) ], lead [O^R =1.083 (95% CI:1.004, 1.167) ], cadmium [O^R =6.658 (95% CI: 2.195, 20.192) ], arsenic [O^R =1.878 (95% CI: 1.343, 2.626) ], and mercury [O^R =2.595 (95% CI: 1.389, 4.848) ] were all risk factors for GDM (P < 0.05). Significant differences were also found between the two groups in HOMA-IR, CRP, MDA, SOD and GSH-Px levels (P < 0.05). The study group showed higher HOMA-IR, CRP and MDA levels, but lower SOD and GSH-Px levels compared to the control group.Conclusion Exposure to air pollutants and heavy metals significantly increases the risk of GDM, likely through mechanisms such as exacerbating insulin resistance, promoting systemic inflammation, and enhancing oxidative stress.