Maternal overweight and obesity modify the association of serum fibroblast growth factor 21 levels with gestational diabetes mellitus: A nested case-control study.

Abstract

To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. Serum FGF21 levels were measured at 6-15weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre-pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre-pregnancy BMI (p for interaction=0.049 and 0.03), and the association was only significant in participants with pre-pregnancy BMI ≥24kg/m2 . When participants were grouped based on pre-pregnancy BMI (≥24 and <24kg/m2 ) and FGF21 levels (≥median and <median), a significant association was observed in those with higher BMI and FGF21 levels (odds ratio, 2.12; 95% CI: 1.41, 3.20) but not in those with either higher BMI or higher FGF21, with a significant additive interaction (relative excess risk due to interaction=1.23; 95% CI: 0.27, 2.20). FGF21 was also correlated with unfavourable glucose and lipid biomarkers as well as adipokines. Elevated serum FGF21 levels in early pregnancy were associated with a higher risk of GDM, particularly among those with overweight/obesity.