Cardiovascular diseases consequences of type 1, type 2 diabetes mellitus and glycemic traits: A Mendelian randomization study

Abstract

Objective

This Mendelian randomization (MR) study aimed to investigate the relationships between type 1 diabetes (T1D), type 2 diabetes (T2D), and glycemic traits, including fasting insulin, fasting glucose, and HbA1c, with cardiovascular diseases (CVDs).

Methods

We selected genetic instruments for predisposition to T1D, T2D, fasting insulin, fasting glucose, and HbA1c based on published genome-wide association studies. Using a 2-Sample MR approach, we assessed associations with 12 common CVDs sourced from the FinnGen and UK Biobank studies, along with stroke subtypes obtained from the GIGASTROKE and MEGASTROKE Consortium.

Results

T1D was associated with SVS. T2D showed associations with AIS, LAA, CES, SVS, coronary heart disease, myocardial infarction, pulmonary embolism, DVT of lower extremities, peripheral vascular diseases. Genetically predicted higher HbA1c levels were associated with eight CVDs. The results of MVMR aligned with the primary findings for T1D and T2D.

Conclusions

T1D and T2D exhibit different genetic predisposition to CVDs. BMI, LDL, and HDL play intermediary roles in connecting TID and T2D to specific types of CVDs, providing insights into the potential underlying pathways and mechanisms involved in these relationships. Strategies aimed at achieving sustained reductions in HbA1c levels may offer potential for reducing the risk of various CVDs.