Associations between Type 2 Diabetes Mellitus, Metabolic Traits, and Abdominal Aortic Aneurysm: A Cross-Ethnic Mendelian Randomization Analysis.

ABSTRACT

BACKGROUND: Evidence suggests that type 2 diabetes mellitus (T2DM) may protect from abdominal aortic aneurysm (AAA). However, it is unclear whether a causal relationship exists between these 2 conditions and, if so, whether it remains consistent among racial groups. METHODS: Cross-ethnic Mendelian randomization (MR) was used to examine the causal relationships between T2DM, metabolic traits, and AAA. Inverse variance weighted (IVW) was the primary analysis tool, supplemented by MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier. Heterogeneity and horizontal pleiotropy were assessed using the Cochran's Q test and MR-Egger intercept, respectively. RESULTS: According to IVW, an inverse correlation between T2DM and AAA was detected in Europeans (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.84-0.99; P = 0.034) and East Asians (OR 0.87, 95% CI 0.77-0.99; P = 0.038). Fasting glucose was inversely associated with AAA in Europeans (OR 0.56, 95% CI 0.33-0.96; P = 0.034) but not in East Asians. In Europeans, fasting insulin was a risk factor for AAA (OR 3.03, 95% CI 1.53-6.01; P = 0.001), while 2-hour glucose was protective (OR 0.67, 95% CI 0.49-0.91; P = 0.011). Glycated hemoglobin (HbA1c) had no effect. Insufficient instrumental variables prevented the evaluation of the relationships of fasting insulin, HbA1c, and 2-hour glucose with AAA in East Asians. CONCLUSIONS: T2DM protects against AAA in Europeans and East Asians. The effects of different glucose metabolism characteristics on AAA may inform AAA treatment.