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Association of History of Gestational Diabetes With Long-term Cardiovascular Disease Risk in a Large Prospective Cohort of US Women

Educational Objective
To prospectively evaluate history of gestational diabetes in relation to incident cardiovascular disease risk.
1 Credit CME
Key Points

Question  Are women with a history of gestational diabetes at an elevated risk of major cardiovascular disease (CVD) events later in life?

Findings  In this cohort study, with follow-up of nearly 90 000 US women older than 26 years, women with a history of gestational diabetes had 43% greater risk of CVD (myocardial infarction or stroke) compared with women without prior gestational diabetes , although absolute rates in this cohort were low. Adhering to healthy lifestyle factors over follow-up mitigated this modestly elevated risk.

Meaning  Although women with prior gestational diabetes have a higher risk of CVD, adhering to a healthy lifestyle may offset this risk.


Importance  Previous studies identify gestational diabetes (GD) as a risk factor for intermediate markers of cardiovascular disease (CVD) risk; however, few are prospective, evaluate hard CVD end points, or account for shared risk factors including body weight and lifestyle.

Objective  To prospectively evaluate history of GD in relation to incident CVD risk.

Design, Setting, and Participants  The Nurses’ Health Study II (NHS II) is an observational cohort study of US female nurses established in 1989, with ongoing follow-up. Biennial questionnaires updated behavioral characteristics, health outcomes, and lifestyle factors. Multivariable Cox models estimated the hazard ratio (HR) and 95% CI for CVD risk. We included 89 479 women who reported at least 1 pregnancy and were free of CVD and cancer at baseline. Follow-up through May 31, 2015, was complete for more than 90% of eligible participants.

Exposures  History of GD was self-reported at baseline (1989) via questionnaire and updated every 2 years.

Main Outcomes and Measures  We observed 1161 incident self-reported nonfatal or fatal myocardial infarction or stroke, confirmed via medical records.

Results  Participants had a mean (SD) age of 34.9 (4.7) years. Adjusting for age, prepregnancy body mass index, and other covariates, GD vs no GD was associated with subsequent CVD (HR, 1.43; 95% CI, 1.12-1.81). Additional adjustment for weight gain since pregnancy and updated lifestyle factors attenuated the association (HR, 1.29; 95% CI, 1.01-1.65). Classifying GD by progression to T2D in relation to CVD risk indicated a positive association for GD with progression to T2D vs no GD or T2D (HR, 4.02; 95% CI, 1.94-8.31), and an attenuated relationship for GD only (HR, 1.30; 95% CI, 0.99-1.71).

Conclusions and Relevance  Gestational diabetes was positively associated with CVD later in life, although the absolute rate of CVD in this younger cohort of predominantly white women was low. This relationship is possibly mediated in part by subsequent weight gain and lack of healthy lifestyle.

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Article Information

Corresponding Author: Cuilin Zhang, MD, PhD, MPH, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Blvd, Room 7B03, Rockville, MD 20852 (

Accepted for Publication: May 7, 2017.

Published Online: October 16, 2017. doi:10.1001/jamainternmed.2017.2790

Author Contributions: Dr Zhang had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Tobias, Stuart, Chavaro, Hu, Manson, Zhang.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Tobias.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Tobias, Stuart, Li.

Administrative, technical, or material support: Chavaro, Hu, Manson.

Study supervision: Manson, Zhang.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by National Institutes of Health (grant No. K01DK103720) to Dr Tobias, and the Nurses’ Health Study II is supported by National Institutes of Health (grant Nos. HL34594 and UM1 CA176726). Dr Zhang is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201000020C).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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