Body mass index modifies the association between transthyretin concentrations and gestational diabetes mellitus across pregnancy trimesters.

BACKGROUND: Gestational diabetes mellitus (GDM), an increasingly prevalent pregnancy complication, poses significant risks to both maternal and fetal health. Early detection and management are crucial, yet current biomarkers for GDM screening are limited. In this context, the present study aims to explore the association between plasma transthyretin (TTR) concentrations and GDM development as well as the interaction between TTR and maternal body mass index (BMI) on the risk of GDM across trimesters. METHODS: A retrospective cohort study included 12,893 pregnant women from the Second Affiliated Hospital of Wenzhou Medical University. Multivariate restricted cubic spline (RCS) models and logistic regression were used to analyze the relationship between TTR concentrations, maternal BMI, and GDM risk. RESULTS: In the first trimester (T1) and the third trimester (T3), there were significant differences in TTR concentrations between the GDM and Non-GDM groups (P < 0.001). As pregnancy progressed, TTR concentrations gradually decreased in the GDM group (all P < 0.05). In the first and second trimesters, GDM risk increased with rising TTR concentrations, and the combined effect of higher TTR concentrations and overweight status significantly increased the risk. In T3, a reverse "J"-shaped nonlinear relationship was observed between TTR concentrations and GDM risk (P for Nonlinear = 0.046), and the combination of higher BMI and lower TTR concentrations significantly increased the risk, showing a positive interaction on the multiplicative scale (ratio of ORs [95% CI] = 1.34 [1.04 to 1.73]). CONCLUSIONS: Elevated TTR concentrations in T1 and lower concentrations in T3 are linked to higher GDM risk. The combination of high TTR concentrations and high BMI further increases GDM risk, suggesting TTR as a potential biomarker for early GDM detection and risk assessment.