Does gestational diabetes mellitus increase the risk of cardiovascular disease? A Mendelian randomization study

Abstract

Purpose: In recent years, epidemiological studies have revealed the relationship between gestational diabetes mellitus (GDM) and cardiovascular disease (CVD). In this study, we utilized Mendelian randomization (MR) to investigate the potential causal impact of GDM on cardiovascular disease for the first time.

Methods: We retrieved summary statistics from published genome-wide association studies. MR was first performed using significant SNPs extracted from the eighth data release of the FinnGen study. Next, a replication analysis for coronary artery disease (CAD) was conducted in another European ancestry population to validate our findings. Finally, mediation analysis was carried out to assess potential mediation effects.

Results: Our data analysis revealed that genetically predicted GDM was significantly associated with increased CAD risk (OR 1.10, 95% CI 1.02-1.18, p 0.006). Replication analysis confirmed a significant genetic association between GDM and CAD (OR 1.07, 95% CI 1.02-1.12, p 0.003) in another European ancestry population. Mediation analysis indicated no significant mediation effect by type 2 diabetes mellitus (T2DM) on the GDM-CAD relationship (mediation effect β [95% CI]: 0.005 [-0.003, -0.017]).

Conclusion: Women with a prior history of GDM face an elevated risk of future CAD. This increased risk of CAD cannot be solely attributed to the subsequent onset of diabetes. Regular CAD risk assessment and primary prevention strategies are of paramount importance for women with a history of GDM.

Keywords: Cardiovascular disease; Gestational diabetes mellitus; Mendelian randomization; Type 2 diabetes.