Prospective Association between Gestational Diabetes and Subsequent Abnormal Liver Function Scores 9 to 16 Years after Pregnancy

Chronic hyperglycemia is a risk factor for liver dysfunction. Women with gestational diabetes mellitus (GDM), glucose intolerance first recognized in pregnancy, may identify a population of individuals at an increased risk for liver complications. However, large prospective studies examining liver function following a GDM pregnancy are lacking. The Diabetes & Women’s Health (DWH) Study (2012-2014) followed women with and without GDM in the Danish National Birth Cohort (DNBC). DNBC was a population-based cohort study of pregnant Danish women (1996-2002). At 9-16 years postpartum, the DWH Study conducted a clinical exam and collected bio-specimens on 607 of 1,274 women with GDM and 619 of a random sample of 1,457 women without GDM during the index DNBC pregnancy. Markers of liver function measured at follow-up included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). Liver function scoring indices were used to assess liver capacity including: nonalcoholic fatty liver disease liver fat score (NAFLD-LFS), fatty liver index (FLI), hepatic steatosis index (HSI), and liver fat percentage. The mean (standard deviation) age (years) at follow-up for women without and with prior GDM was 43.4 (4.5) and 43.8 (4.6), respectively. Women with prior GDM had an increased risk at follow-up of elevated NAFLD-LFS (Adjusted Relative risk [RR], 2.34; 95% CI, 1.68-3.27), FLI (RR, 1.59; 95% CI, 1.27-1.99), and HSI (RR, 1.44; 95% CI, 1.21-1.71) adjusted for pre-pregnancy BMI and other relevant risk factors compared to women without prior GDM. Women with prior GDM also had a significantly higher fatty liver percentage (Adjusted difference (%), 1.93; 95% CI, 1.10-2.77). Women with GDM during pregnancy were at an increased risk for subsequent abnormal liver function 9-16 years postpartum. GDM may serve as another risk indicator for the early identification and prevention of liver dysfunction.