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.