Association of gestational diabetes mellitus with overall and type specific cardiovascular and cerebrovascular diseases: systematic review and meta-analysis

OBJECTIVE: To quantify the risk of overall and type specific cardiovascular and cerebrovascular diseases as well as venous thromboembolism in women with a history of gestational diabetes mellitus. DESIGN: Systematic review and meta-analyses. DATA SOURCES: PubMed, Embase, and the Cochrane Library from inception to 1 November 2021 and updated on 26 May 2022. REVIEW METHODS: Observational studies reporting the association between gestational diabetes mellitus and incident cardiovascular and cerebrovascular diseases were eligible. Data, pooled by random effects models, are presented as risk ratios (95% confidence intervals). Certainty of evidence was appraised by the Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: 15 studies rated as moderate or serious risk of bias were included. Of 513 324 women with gestational diabetes mellitus, 9507 had cardiovascular and cerebrovascular disease. Of more than eight million control women without gestational diabetes, 78 895 had cardiovascular and cerebrovascular disease. Compared with women without gestational diabetes mellitus, women with a history of gestational diabetes mellitus showed a 45% increased risk of overall cardiovascular and cerebrovascular diseases (risk ratio 1.45, 95% confidence interval 1.36 to 1.53), 72% for cardiovascular diseases (1.72, 1.40 to 2.11), and 40% for cerebrovascular diseases (1.40, 1.29 to 1.51). Women with gestational diabetes mellitus showed increased risks of incident coronary artery diseases (1.40, 1.18 to 1.65), myocardial infarction (1.74, 1.37 to 2.20), heart failure (1.62, 1.29 to 2.05), angina pectoris (2.27, 1.79 to 2.87), cardiovascular procedures (1.87, 1.34 to 2.62), stroke (1.45, 1.29 to 1.63), and ischaemic stroke (1.49, 1.29 to 1.71). The risk of venous thromboembolism was observed to increase by 28% in women with previous gestational diabetes mellitus (1.28, 1.13 to 1.46). Subgroup analyses of cardiovascular and cerebrovascular disease outcomes stratified by study characteristics and adjustments showed significant differences by region (P=0.078), study design (P=0.02), source of data (P=0.005), and study quality (P=0.04), adjustment for smoking (P=0.03), body mass index (P=0.01), and socioeconomic status (P=0.006), and comorbidities (P=0.05). The risk of cardiovascular and cerebrovascular diseases was, however, attenuated but remained significant when restricted to women who did not develop subsequent overt diabetes (all gestational diabetes mellitus: 1.45, 1.33 to 1.59, gestational diabetes mellitus without subsequent diabetes: 1.09, 1.06 to 1.13). Certainty of evidence was judged as low or very low quality. CONCLUSIONS: Gestational diabetes mellitus is associated with increased risks of overall and type specific cardiovascular and cerebrovascular diseases that cannot be solely attributed to conventional cardiovascular risk factors or subsequent diabetes.