Serum uric acid levels and risk of cardiovascular disease in type 2 diabetes: results from a cross-sectional study and Mendelian randomization analysis

AIMS: Serum uric acid (SUA) levels have been previously linked to a higher risk of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) according to various observational studies. However, whether this association is causally linked or simply influenced by confounding factors is unclear. Therefore, this study utilized Mendelian randomization (MR) analysis to explore the causality between SUA levels and the risk of CVD in individuals with T2D. METHODS: Our study cohort consisted of 5723 participants who were diagnosed with T2D in the National Health and Nutrition Examination Survey (NHANES) from 1999-2018. The study assessed the association between SUA levels and the risk of CVD using a multivariable logistic regression model. To further examine causality between SUA levels and CVD, a two-sample MR study was conducted utilizing genetic data from genome-wide association studies (GWAS) involving over 140,000 individuals. The main MR analysis employed the inverse-variance-weighted (IVW) method. Additionally, several sensitivity analyses were performed to evaluate the robustness and pleiotropy of the results. RESULTS: In the cross-sectional study, after multivariable adjustment, participants with SUA levels >6.7 mg/dL exhibited odds ratios (ORs) of 1.51 (95% CI: 1.01-2.26, p=0.049) for heart failure, 1.02 (95% CI: 0.69-1.50, p=0.937) for coronary heart disease, 1.36 (95% CI: 0.78-2.38, p=0.285) for angina, and 1.22 (95% CI: 0.80-1.85, p=0.355) for myocardial infarction when compared to participants with SUA levels ≤ 4.6 mg/dL. However, in the IVW analysis, no causality between SUA levels and the risk of heart failure was observed (OR = 1.03, 95% CI: 0.97-1.09, p = 0.293). The secondary analysis yielded similar results (OR = 1.05, 95% CI: 0.96-1.14, p = 0.299). The sensitivity analyses further supported our primary findings. CONCLUSION: Based on the MR study, we did not find supporting evidence for a causal association between SUA levels and the risk of heart failure.