Mendelian randomization did not support the causal effect of diabetes on aortic diseases

Area of Science:

• Cardiovascular Genetics
• Metabolic Diseases
• Epidemiology

Background:

• Observational studies suggest an inverse relationship between diabetes and aortic diseases (aneurysm, dissection).
• The causal basis for this observed association remains undetermined.
• Investigating genetic causality is crucial to understand the diabetes-aortic disease relationship.

Purpose of the Study:

• To determine the causal effect of diabetes and related glycemic traits on aortic diseases.
• Utilizing Mendelian randomization to assess genetic predispositions for diabetes and their impact on aortic aneurysm and dissection risk.

Main Methods:

• Mendelian randomization analysis using summary-level data from large genome-wide association studies.
• Primary analysis employed the inverse-variance weighted (IVW) method.
• Sensitivity analyses included weighted median, MR-Egger, and multivariable MR to ensure robustness.

Main Results:

• No causal association was found between type 1 diabetes, type 2 diabetes, fasting glucose, fasting insulin, or glycated hemoglobin and aortic dissection.
• Similarly, no causal effects were observed for these diabetes-related traits on aortic aneurysm.
• Sensitivity analyses confirmed these findings, with no evidence of directional pleiotropy.

Conclusions:

• Diabetes does not appear to have a causal effect on the risk of aortic dissection or aortic aneurysm.
• The inverse associations reported in prior observational studies are likely attributable to confounding factors or reverse causation.
• Genetic evidence supports the absence of a direct causal link between diabetes and aortic disease development.