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

Date Published: 2026-09-15

Abstract:
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.

Introduction:
Gestational diabetes mellitus (GDM) affects approximately one in six pregnancies globally ( 1 ). Beyond immediate obstetric implications, it confers long-term cardiometabolic risks to both mother and offspring, including future type 2 diabetes and cardiovascular disease ( 2 , 3 ). In routine practice, however, GDM screening is not performed until 24–28 weeks of gestation ( 4 ). This creates a temporal gap: metabolic susceptibility may precede detectable dysglycemia by weeks or months. Early-pregnancy markers that…

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