Gestational diabetes mellitus, body mass index, and cardiometabolic multimorbidity: A prospective cohort study

Purpose: Gestational diabetes mellitus (GDM) could increase the risks of type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, evidence on its association with cardiometabolic multimorbidity (CMM) was limited. This study aimed to evaluate the association between GDM and the prevalence, incidence, patterns, and progression of CMM; and the role of body mass index (BMI) in such association. Methods: This study included 203,372 women who have given birth in UK Biobank. The diagnoses of GDM and cardiometabolic diseases (including stroke, coronary heart disease [CHD], and T2DM) were reported by participants or obtained through linkage to inpatient hospital data until 31st December 2020. BMI was assessed at the baseline assessment. CMM was defined as having two or more of included cardiometabolic diseases. Logistic regression models and Cox proportional hazard models were used to assess the association between GDM and CMM, and the modifications on both additive and multiplicative scales were assessed to evaluate the effect of BMI on such association. Results: A total of 1217 women had a history of GDM, 2351 participants had CMM at the end of follow-up and 1601 was newly diagnosed during follow-up. GDM was associated with higher prevalence (odds ratio [OR]=4.64, 95 % confidence interval [95 % CI]=3.54-6.08) and incidence (hazard ratio [HR]=3.62, 95 % CI=2.62-5.00) of CMM. In particular, GDM was associated with higher odds of T2DM, coexisting T2DM and vascular disease, and T2DM followed by vascular disease. Formal testing for effect modification suggested multiplicative modification by BMI for the association between GDM and incident CMM. Conclusions: GDM was associated with CMM in women's late life, with multiplicative modification effects of BMI. Our results suggest that maternal and lifestyle interventions (e.g., weight management) are warranted for the primary and secondary prevention of CMM, particularly in women with a history of GDM.