Gestational Diabetes Mellitus and the Risks of Overall and Type-Specific Cardiovascular Diseases: A Population- and Sibling-Matched Cohort Study

<b>OBJECTIVE</b> <p>To evaluate associations between gestational diabetes mellitus (GDM) and various incident cardiovascular disease (CVD) endpoints, considering the effects of mediating role of type 2 diabetes and shared environmental/familial factors.</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>This population-based cohort study included 1002486 parous women in Denmark during 1978-2016. We used Cox regression to (i) examine the associations of GDM with overall and type-specific CVDs using full-cohort and sibling-matched analysis; (ii) quantify the impact of type 2 diabetes after GDM using mediation analysis; and (iii) assess whether these associations were modified by pre-pregnancy obesity or maternal history of CVD.</p> <p><b>RESULTS</b></p> <p>Women with a history of GDM had a 40% increased overall CVD risk (hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 1.35-1.45). Sibling-matched analyses yielded similar results(HR, 1.44; 95%CI, 1.28-1.62). Proportion of association between GDM and overall CVD explained by subsequent type 2 diabetes was 23.3%(15.4%-32.8%). We observed increased risks of specific CVDs, including 65% increased stroke risk and more than two-fold risks for myocardial infarction, heart failure, and peripheral artery disease. The elevated overall risks were more pronounced among women with GDM and pre-pregnancy obesity or maternal history of CVD. </p> <p><b>CONCLUSIONS</b></p> <p>A history of GDM was associated with increased risks of overall and specific CVDs. Increased risks were partly explained by subsequent type 2 diabetes and the need to identify other pathways remains important. Continuous monitoring of women with a history of GDM, especially those with pre-pregnancy obesity or maternal history of CVD, may provide better opportunities to reduce their cardiovascular risk.</p>