Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis
Women who develop gestational diabetes mellitus (GDM) have an elevated lifetime risk of type 2 diabetes mellitus. Recently, a series of studies has suggested that women with GDM also have an increased risk of cardiovascular disease (CVD). However, it is unclear if this risk is dependent upon the intercurrent development of type 2 diabetes. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of GDM on future risk of incident CVD and to ascertain the role of type 2 diabetes in this regard.
We systematically searched the PubMed and EMBASE databases for observational studies that evaluated the association of GDM with subsequent CVD, with publication between 1 January 1950 and 30 August 2018. Two independent reviewers extracted data and the analysis was performed in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. RRs were calculated using a random-effects model to assess the predictive value of GDM for future cardiovascular events. To evaluate whether incident type 2 diabetes in the GDM population influenced the association with CVD, we used meta-regression models followed by sensitivity analyses restricted to women who did not develop type 2 diabetes during follow-up.
A pooled analysis of nine studies yielded data from 5,390,591 women (101,424 cardiovascular events). Compared with those who did not have GDM, women with GDM had a twofold higher risk of future cardiovascular events (RR 1.98 [95% CI 1.57, 2.50]). Meta-regression analysis showed that the rates of incident type 2 diabetes across the studies did not affect this risk (p = 0.34). Moreover, when restricted to women who did not develop type 2 diabetes, GDM remained associated with a 56% higher risk of future cardiovascular events (RR 1.56 [95% CI 1.04, 2.32]). GDM conferred a 2.3-fold increased risk of cardiovascular events in the first decade postpartum (RR 2.31 [95% CI 1.57, 3.39]).
The diagnosis of GDM identifies young women who have a twofold higher risk of cardiovascular events postpartum compared with their peers. This risk is not dependent upon intercurrent type 2 diabetes and is apparent within the first decade after pregnancy. Thus, even without progressing to type 2 diabetes, women with GDM comprise an at-risk population for CVD and hence a potential opportunity for early risk factor surveillance and risk modification.
KeywordsCardiovascular disease Gestational diabetes Meta-analysis Risk factors Systematic review Type 2 diabetes Women’s health
Gestational diabetes mellitus
CKK holds a Canadian Diabetes Association Clinician-Scientist award. RR holds the Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at Mount Sinai Hospital, and his research programme is supported by the Sun Life Financial Program to Prevent Diabetes in Women.
CKK and RR conceived the systematic review and analysis plan. CKK and SC selected studies for inclusion and abstracted data. CKK performed the statistical analyses. CKK and RR interpreted the data. All authors wrote the first draft, critically revised the manuscript for important intellectual content and approved the final draft. RR is guarantor of this work.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Duality of interest
CKK has received grants from Boehringer Ingelheim, outside the submitted work. SC has nothing to disclose. RR has received grants and personal fees from Novo Nordisk, grants from Boehringer Ingelheim, personal fees from Eli Lilly, personal fees from Takeda, personal fees from Sanofi, and grants and personal fees from Merck, outside the submitted work.
- 11.Wells GA, Shea B, O’Connell D et al The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 10 Feb 2019
- 19.Daly B, Toulis KA, Thomas N et al (2018) Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: a population-based cohort study. PLoS Med 15(1):e1002488. https://doi.org/10.1371/journal.pmed.1002488 CrossRefPubMedGoogle Scholar
- 27.Retnakaran R, Qi Y, Connelly PW, Sermer M, Hanley AJ, Zinman B (2010) Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta-cell dysfunction and fasting glycaemia. Diabetologia 53(2):268–276. https://doi.org/10.1007/s00125-009-1600-8 CrossRefPubMedGoogle Scholar
- 28.Retnakaran R, Qi Y, Connelly PW, Sermer M, Hanley AJ, Zinman B (2010) The graded relationship between glucose tolerance status in pregnancy and postpartum levels of LDL cholesterol and apolipoprotein B in young women: implications for future cardiovascular risk. J Clin Endocrinol Metab 95(9):4345–4453. https://doi.org/10.1210/jc.2010-0361 CrossRefPubMedGoogle Scholar