This cohort study included 44,609 singleton pregnant women across three medical centers. The exposure was serum uric acid levels measured prior to 20 weeks of gestation, with a comparator defined as levels below 240 µmol/L. The primary outcome was gestational diabetes mellitus (GDM), with secondary outcomes including GDM requiring insulin therapy (GDMA2) and GDM complicated by pre-eclampsia (GDM&PE).
For the primary outcome, a nonlinear relationship was observed with a turning point at 240 µmol/L. Compared to the reference, the odds ratio (OR) for GDM was 1.47 (95% CI: 1.37-1.58) for levels of 240–360 µmol/L and 2.60 (95% CI: 1.94-3.47) for levels ≥360 µmol/L. Positive associations were also reported for GDMA2 and GDM&PE, though effect sizes and p-values were not reported.
A Mendelian randomization analysis suggested a causal relationship, with an OR of 1.122 (95% CI: 1.016-1.239, p = 0.023). Safety data, including adverse events and discontinuations, were not reported. Key limitations include the observational design, which cannot prove causation, and the lack of reported follow-up duration or absolute event numbers.
Practice relevance suggests monitoring serum uric acid in early pregnancy may help risk stratify individuals for GDM management. However, the distinction between association and causation, and between surrogate and clinical outcomes, must be considered.
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BackgroundThis study aimed to investigate the association between serum uric acid level in the before 20 weeks of gestation and gestational diabetes mellitus (GDM).MethodsA 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 (GDM&PE). 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.ResultsThe 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).ConclusionElevated 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.