Association between First-Trimester Serum Uric Acid Levels and Development of Gestational Diabetes Mellitus

Abstract

Background: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication, yet current screening occurs only at 24–28 weeks, missing early intervention opportunities. Uric acid, an inexpensive and routinely measured first-trimester biomarker, has been mechanistically linked to insulin resistance, making it a promising candidate for early risk stratification.

Aims: To investigate the association between first-trimester serum uric acid levels and subsequent GDM development, determine independent predictive value after confounder adjustment, establish an optimal cut-off, and examine dose-response relationships.

Methods: This observational cohort study enrolled 150 pregnant women at first-trimester booking and followed them until delivery. Serum uric acid was measured as the exposure, and GDM diagnosed via OGTT at 24–28 weeks. Statistical analyses included t-tests, Mann-Whitney U tests, logistic regression, ROC curve analysis, and quartile trend testing.

Results: Women who developed GDM (n=28, 18.7%) had significantly higher first-trimester uric acid than those who did not (5.10 vs. 3.98 mg/dL; p<0.001). Maternal age and BMI were similar between groups. Uric acid independently predicted GDM (unadjusted OR 6.66 per 1 mg/dL; 95% CI 3.17–13.99). ROC analysis showed good discrimination (AUC 0.839; 95% CI 0.744–0.934), with Youden-optimal cut-off at 4.45 mg/dL (sensitivity 89.3%, specificity 73.0%, NPV 96.7%). A strong dose-response trend was observed, with GDM incidence rising from 2.6% in the lowest quartile to 44.7% in the highest (p<0.001).

Conclusion: First-trimester serum uric acid demonstrates good predictive accuracy and a clear dose-response relationship with GDM, with high NPV supporting its use as a low-cost triage tool to identify very-low-risk women. However, limited GDM events (n=28) mean the adjusted estimates and cut-off require validation in larger, adequately powered cohorts before clinical implementation. The biomarker is not a replacement for formal OGTT screening.