Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy

Abstract

Abstract To evaluate the role of high glucose variability (High-GV) in early pregnancy as a potential mediating factor between pre-pregnancy overweight/obesity and late-onset HDP (LoHDP), where effective preventive strategies remain limited. This multicenter retrospective study analyzed data from 802 pregnancies across 14 facilities. Pregnancies with a 75 g-OGTT performed by 20 weeks of gestation were included. Structural equation modeling (SEM) was used to evaluate direct and indirect effects of body mass index (BMI), High-GV, and covariates (e.g., age, ART, primiparity) on LoHDP. Overweight/obese women had significantly higher rates of High-GV (26.1 vs. 16.4%, p = 0.001) and LoHDP (17.6 vs. 7.9%, p < 0.001) compared to non-overweight/obese women. SEM revealed that BMI influenced LoHDP through both direct and indirect pathways. BMI had a direct effect on LoHDP (β = 0.20, p < 0.01), and an indirect effect mediated by High-GV, with BMI significantly associated with High-GV (β = 0.15, p < 0.01), and High-GV positively associated with LoHDP (β = 0.12, p < 0.01). In Non-GDM pregnancies, High-GV showed an even stronger association with LoHDP (β = 0.25, p < 0.001). This study identifies High-GV as a key mediator linking pre-pregnancy overweight/obesity to LoHDP. These findings suggest that targeting glucose variability in early pregnancy could mitigate LoHDP risk, particularly in overweight/obese women, regardless of GDM status. Future preventive strategies should integrate multifaceted approaches addressing maternal BMI and glucose regulation to improve maternal and neonatal outcomes.