Associations between gestational diabetes and cardiovascular disease largely operate independently of postpartum causal pathways: A population-based cohort study in England

Background Gestational diabetes mellitus (GDM) is associated with increased risk of developing type 2 diabetes and cardiovascular disease (CVD). Here we explore whether the associations are mediated by development of type 2 diabetes and other CVD risk factors. Methods The Exploring Long-term Outcomes following PrEgnancy affected by GDM (ELOPE-GDM) study is a population-based matched cohort study, containing 43 572 records of women diagnosed with GDM matched with 174 288 records of non-GDM women. We used Cox proportional hazards models to assess the risk of GDM on CVD, ischemic heart disease (IHD) and stroke/TIA and quantified the proportions of these effects mediated by the progression to type 2 diabetes, hypertension or dyslipidaemia using causal mediation analysis. Results There were significant associations between GDM and CVD; (adjusted HR 1.58 (95% CI 1.27–1.97)), IHD (1.83 (1.35–2.49)) and stroke/TIA (1.43 (1.06–1.95)). There were strong associations between GDM and developing type 2 diabetes (OR 13.90 (95% CI 13.19–14.51)), hypertension (1.87 (1.781–1.92)), dyslipidaemia (1.80 (1.76–1.84)) or any of these postpartum mediators (1.67 (1.63–1.71)). However, most of the effect of GDM on CVD was not attributed to the overall mediating effects of type 2 diabetes (36% (95% CI 8%–64%)), hypertension (15% (5%–24%)), dyslipidaemia (37% (18%–55%)) or a combination of these conditions (32% (11%–53%)) which developed after pregnancy. Conclusion These findings emphasise the need for comprehensive cardio metabolic screening following a pregnancy affected by GDM.