Manifestations of Vascular and Metabolic Disorders in Pregnancy and Type 2 Diabetes Risk

Exaggerated response reflective of the vascular and metabolic disorders in pregnancy as seen in preeclampsia (PE) and gestational diabetes (GDM) is proposed to herald future vascular and metabolic disorders.Studies that comprehensively examined associations of both PE and GDM with future risk of type 2 diabetes (T2DM) are scant.We prospectively examined these associations among 65,719 eligible women in Nurses' Health Study II.After 10 years of follow-up, 1025 of them developed T2DM.Women with histories of PE and/or GDM had 1.7 to 6.4-fold higher risk of T2DM compared with those without these histories.After adjustment for age and body bass index (BMI), the relative risks (RR) (95% CI) of T2DM were 1.7 (1.5, 2.0) related to PE only, 5.0 (4.2, 6.1) for GDM only, and 6.4 (5.1, 8.2) for joint effects of GDM and PE.These significant associations persisted across sub-groups defined by nulliparity (yes/no), family history of T2DM (yes/no), and smoking status (yes/no), etc. Notably, overall body adiposity significantly modified the observed associations; risks of type 2 DM related to history of GDM and history of both GDM and PE (RR (95% CI); 8.7 (4.7, 16.3) and 12.9 (5.3, 31.3),respectively) were substantially higher in lean women (BMI <25 kg/m 2 ) than in overweight or obese women (BMI Y25 kg/m 2 ) (RR (95% CI); 4.9 (3.8, 6.2) and 5.5 (3.3, 7.0), respectively; adjusted P for interaction 0.004).Findings from the present study provided strong evidence that exaggerated response reflective of the metabolic disorders in pregnancy predicted future risk of T2DM.Common genetic risk factors might explain these associations, particularly among women without modifiable T2DM risk factors.