Early-pregnancy BMI-derived adiposity change rate and gestational diabetes mellitus risk: modification by a fatty liver index-defined hepatic-metabolic phenotype.

Gestational diabetes mellitus (GDM) is commonly diagnosed at 24-28 weeks of gestation; however, metabolic susceptibility that precedes dysglycemia may emerge earlier. We examined whether the rate of early pregnancy body mass index (BMI)-derived estimated body fat percentage (eBFP) change was associated with subsequent GDM, and whether this association differed according to an early hepatic-metabolic phenotype defined by the natural log-transformed fatty liver index (FLI_Ln). This secondary analysis used de-identified data from a prospective Korean pregnancy cohort and included 583 singleton pregnant women without pregestational diabetes, of whom 37 developed GDM. eBFP was estimated from BMI and maternal age, and the early-pregnancy eBFP change rate was calculated from pre-pregnancy to 10-14 weeks of gestation and scaled so that each one-unit increase represented a 0.1 percentage-point/week higher change rate. Multivariate logistic regression, restricted cubic splines, threshold analysis, subgroup interaction testing, exploratory mediation analysis, and propensity score-matched sensitivity analyses were also performed. After adjustment for maternal age, parity, pre-pregnancy BMI, a higher eBFP change rate was associated with increased odds of subsequent GDM (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.14-2.21; P = 0.006), with an approximately linear dose-response pattern. The FLI_Ln showed a nonlinear association with GDM, with a data-derived threshold of 2.90. The eBFP change rate-GDM association was evident among women with FLI_Ln ≥2.90 (OR, 1.82; 95% CI, 1.22-2.71; P = 0.004), but not among those with FLI_Ln <2.90 (OR, 0.51; 95% CI, 0.22-1.20; P = 0.123; P for interaction = 0.018). Exploratory mediation analyses suggested that FLI_Ln partially accounted for the observed association, although the magnitude of this mediation was imprecisely estimated. In this secondary cohort analysis, a faster early-pregnancy BMI-derived adiposity change was associated with a higher risk of GDM, particularly among women with an elevated composite hepatic-metabolic phenotype. These findings support an early adiposity-hepatic metabolic susceptibility framework for GDM risk enrichment but require external validation before clinical application.