History of Gestational Diabetes Mellitus and Future Risk of Atherosclerosis in Mid‐life: The Coronary Artery Risk Development in Young Adults Study

BACKGROUND History of gestational diabetes mellitus (GDM) increases lifetime risk of type 2 diabetes (DM) and the metabolic syndrome (MetS), which increase risk of cardiovascular disease. It is unclear, however, whether GDM increases risk of early atherosclerosis independent of pre-pregnancy obesity and subsequent metabolic disease. METHODS AND RESULTS Of 2787 women (18 to 30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we studied 898 (47% black) who were free of DM and heart disease at baseline (1985-1986), delivered ≥1 post-baseline births, reported GDM history, and had common carotid intima media thickness (ccIMT, mm) measured in 2005-2006. We used multivariable linear regression to assess associations between GDM and ccIMT adjusted for race, age, parity, and pre-pregnancy cardiometabolic risk factors. We assessed mediators (weight gain, insulin resistance, blood pressure), and effect modification by incident DM or MetS during the 20-year period. Of the 898 women, 119 (13%) reported GDM (7.6 per 100 deliveries). Average age was 31 at last birth and 44 at ccIMT measurement for GDM and non-GDM groups. Unadjusted mean ccIMT was 0.023 mm higher for GDM than non-GDM groups (P=0.029), but pre-pregnancy BMI attenuated the difference to 0.016 mm (P=0.109). In 777 women without subsequent DM or the MetS, mean ccIMT was 0.023 mm higher for GDM versus non-GDM groups controlling for race, age, parity, and pre-pregnancy BMI (0.784 versus 0.761, P=0.039). Addition of pre-pregnancy insulin resistance index had minimal impact on adjusted mean net ccIMT difference (0.22 mm). Mean ccIMT did not differ by GDM status among 121 women who developed DM or the MetS (P=0.58). CONCLUSIONS History of GDM may be a marker for early atherosclerosis independent of pre-pregnancy obesity among women who have not developed type 2 diabetes or the metabolic syndrome.