Gestational diabetes and subsequent risk of type 2 diabetes and metabolic dysfunction-associated steatotic liver disease in a commercially insured U.S. Pregnancy cohort.

AIMS: Gestational diabetes mellitus (GDM) is a common pregnancy complication and marker of subsequent metabolic risk. Whether GDM increases metabolic dysfunction-associated steatotic liver disease (MASLD) directly or mainly through progression to type 2 diabetes (T2D) remains unclear.

METHODS

Using MerativeTM MarketScan® Commercial Database (2007-2023), we assembled a retrospective cohort of females aged 12-55 years with ≥ 20 gestational weeks and continuous enrollment from 90 days pre-pregnancy through ≥ 1 year postpartum. GDM was identified by ICD codes during pregnancy. Claims-diagnosed T2D and MASLD were ascertained after delivery for up to 15 years. We estimated adjusted hazard ratios (HRs) using Cox models and used a semi-Markov multistate model to quantify direct and T2D-mediated associations.

RESULTS

Among 1,363,040 women (mean follow-up 3.1 years), 8.43% had GDM. GDM was associated with incident T2D (adjusted HR 11.96; 95% CI 11.55-12.38) and MASLD (2.29, 2.15-2.43). Multistate models showed a direct GDM-to-MASLD association (2.16, 2.02-2.31) and a dominant indirect pathway through T2D. In model-based counterfactual projections, preventing post-GDM T2D reduced projected 5-year MASLD risk from 13.30% to 0.93% (0.45% without GDM).

CONCLUSIONS

In this claims-based cohort, GDM confers increased risk of T2D and MASLD, with most excess MASLD risk acted through T2D. Postpartum strategies prioritizing diabetes prevention may markedly attenuate liver disease burden in this high-risk population.