History of gestational diabetes and incident nonalcoholic fatty liver disease: The Kangbuk Samsung Health Study.

Abstract

We examined the relationship between a prior history of gestational diabetes mellitus (pGDM) and risk of incident nonalcoholic fatty liver disease (NAFLD) and investigated the effect of insulin resistance or development of diabetes as mediators of any association. We performed a retrospective cohort study of 64,397 Korean parous women without NAFLD. The presence of, and the severity of NAFLD at baseline and follow-up were assessed using liver ultrasonography. Cox proportional hazards models were used to determine adjusted hazard ratios (aHRs) for incident NAFLD according to a self-reported GDM history, adjusting for confounders as time-dependent variables. Mediation analyses were performed to examine whether diabetes or insulin resistance may mediate the association between pGDM and incident NAFLD. During a median follow-up of 3.7 years, 6,032 women developed incident NAFLD (of whom 343 had moderate-to-severe NAFLD). Multivariable aHRs (95% confidence intervals) comparing women with time-dependent pGDM to the reference group (no pGDM) was 1.46 (1.33-1.59) and 1.75 (1.25-2.44) for incident overall NAFLD and moderate-to-severe NAFLD, respectively. These associations remained significant in analyses restricted to women with normal fasting glucose <100 mg/dl or that excluded women with prevalent diabetes at baseline or incident diabetes during follow-up. Diabetes and insulin resistance (HOMA-IR) each mediated <10% of the association between pGDM and overall NAFLD development. A prior history of GDM is an independent risk factor for NAFLD development. Insulin resistance, measured by HOMA-IR, and development of diabetes each explained only <10% of the association between GDM and incident NAFLD.