Abstract
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes and has maternal health implications reaching beyond the perinatal period. We aimed to investigate the incidence and severity of cardiovascular and metabolic morbidity in women with previous GDM in a Danish population and to study whether proxies of impaired beta cell function-insulin treatment during GDM pregnancy and development of subsequent manifest diabetes mellitus-influence incident risk of cardiovascular and metabolic morbidity. METHODS: A nationwide register-based cohort study was conducted on the complete cohort of 700,648 women delivering in Denmark during 1997-2018. The exposure variable was GDM and primary outcome was overall cardiovascular and metabolic morbidity. Secondary outcomes were major cardiovascular disease (ischemic heart disease, heart failure, and/or stroke/transient cerebral ischemia), hypertension, dyslipidemia, and venous thrombosis. Severity of morbidity was assessed using number of hospital contacts with diagnosis codes related to cardiovascular and metabolic morbidity and number of redemptions of prescribed medication related to cardiovascular and metabolic morbidity in women who developed cardiovascular and metabolic morbidity after pregnancy. RESULTS: The median follow-up period was 10.2-11.9 years with a total range of 0-21.9 years. GDM was associated with increased risk of any cardiovascular and metabolic morbidity (adjusted HR 2.13 [95% CI 2.07-2.20]), major cardiovascular disease (adjusted HR 1.69 [95% CI 1.55-1.84]), hypertension (adjusted HR 1.89 [95% CI 1.82-1.96], dyslipidemia (adjusted HR 4.48 [95% CI 4.28-4.69]), and venous thrombosis (adjusted HR 1.32 [95% CI 1.16-1.50]). Insulin treatment during pregnancy and subsequent development of manifest diabetes exacerbated the risk estimates. Previous GDM was associated with more hospital contacts and more redeemed prescriptions in women developing cardiovascular and metabolic morbidity (p < 0.001). CONCLUSIONS: Previous GDM was associated with significantly higher risk of cardiovascular and metabolic morbidity, especially incident dyslipidemia. Risks were exacerbated by proxies of beta cell impairment. Severity of morbidity was significantly worse if GDM preceded cardiovascular and metabolic morbidity.