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

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posted on 11.11.2021, 16:27 by Yongfu Yu, Melissa Soohoo, Henrik Toft Sørensen, Jiong Li, Onyebuchi A. Arah
OBJECTIVE

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.

RESEARCH DESIGN AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Funding

This study was supported by unrestricted grants from the Independent Research Fund Denmark (DFF-6110-00019B, DFF 9039-00010B and DFF-1030-00012B); grants from the Nordic Cancer Union (R275-A15770); a grant from the Karen Elise Jensens Fond (2016); a grant from the Novo Nordisk Foundation (NNF18OC0052029), a grant from Shanghai Rising-Star Program (21QA1401300), a grant from the National Natural Science Foundation of China (No. 82073570), a grant from an NIH grant (UL1TR001881) from the National Center for Advancing Translational Science, and the facilities and resources provided by the California Center for Population Research at UCLA (CCPR) which receives core support (grant R24HD041022) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health.

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