Associations of gestational diabetes mellitus with the risk of cardiometabolic diseases: results from NHANES and mendelian randomization analyses

Gestational diabetes mellitus (GDM) is associated with an increased risk of long-term cardiometabolic diseases beyond the perinatal period. This study aimed to investigate the association and the potential causality between GDM and subsequent risk of cardiometabolic diseases, as well as to evaluate the effect of GDM onset age on the diseases. Data were from 10,251 women with at least one live birth in the NHANES 2007-2018. Survey-weighted logistic regression analysis was performed to investigate the association. Subsequently, the inverse variance weighted (IVW) and other supplementary approaches of two-sample Mendelian randomization (MR) were used to verify the causal association. Women with a history of GDM had an increased risk of obesity (OR: 1.67, 95%CI: 1.38–2.01), hyperlipidemia(OR: 1.28, 95%CI: 1.02 – 1.61), type 2 diabetes mellitus (T2DM) (OR: 5.39, 95%CI: 4.25–6.85), metabolic syndrome (MetS) (OR: 1.62, 95%CI: 1.28–2.05), cardiovascular diseases (OR: 1.61, 95%CI: 1.04–2.52) and coronary heart disease (CHD) (OR: 1.89, 95%CI: 1.17–3.06). Besides, participants diagnosed with GDM at a young age were more prone to developing cardiometabolic diseases. Furthermore, a causal link between GDM and the risk of T2DM (OR: 1.54, 95%CI: 1.09–2.17) and CHD (OR: 1.08, 95%CI: 1.04–1.12) was supported by the IVW method of the MR analysis. Mediation analyses of observational and MR study consistently revealed that T2DM partially mediated the association between GDM and incident CHD. GDM was significantly associated with an increased risk of cardiometabolic diseases, and a younger age of GDM onset indicated a higher risk. Moreover, a causal association of GDM with the risk of T2DM and CHD was identified.