Association between serum uric acid and the risk of gestational diabetes mellitus: a multicenter cohort study

Background This study aimed to investigate the association between serum uric acid level in the before 20 weeks of gestation and gestational diabetes mellitus (GDM). Methods A retrospective cohort study was conducted involving 44,609 singleton pregnant women from three medical centers from January 2018 to June 2024. The primary exposure was serum uric acid levels measured prior to 20 weeks of gestation. The main outcome of interest was GDM, with secondary outcomes including GDM requiring insulin therapy (GDMA2) and GDM complicated by pre-eclampsia (GDMPE). Statistical methods such as smooth curve fitting, threshold effects, multivariate logistic regression, and subgroup analysis were employed to examine the relationship between uric acid and GDM. Additionally, a two-sample Mendelian randomization (MR) study was performed using genetic data from Genome-Wide Association Studies (GWAS) of serum uric acid and GDM. Results The cohort study revealed a nonlinear relationship between uric acid level and GDM risk, with a turning point of 240 μmol/L. After adjusting for confounders, the odds ratio for GDM was 1.47(95% CI: 1.37-1.58) for uric acid level between 240 ~ 360 μmol/L compared to level below 240 μmol/L, the odds ratio for GDM was 2.60 (95% CI: 1.94-3.47) for uric acid levels ≥ 360 μmol/L. Similar positive associations were observed between uric acid level and GDMA2 and GDM PE, which were consistent across subgroup analyses. The MR analysis indicated a causal relationship between uric acid and GDM (OR = 1.122, 95% CI: 1.016-1.239, p = 0.023). Conclusion Elevated serum uric acid levels in the before 20 weeks of gestation are associated with an increased risk of GDM. Monitoring serum uric acid in early pregnancy helps in risk stratification for the management of individuals at high risk of GDM.