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

Ying He; Jincheng Feng; Bo Zhang; Qiong Wu; Yongjie Zhou; Diao He; Daofeng Zheng; Jiayin Yang

doi:10.3389/fendo.2023.1251451

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

Front Endocrinol (Lausanne). 2023 Nov 7:14:1251451. doi: 10.3389/fendo.2023.1251451. eCollection 2023.

Authors

Ying He^#¹, Jincheng Feng^#², Bo Zhang^{1

3}, Qiong Wu¹, Yongjie Zhou¹, Diao He¹, Daofeng Zheng¹, Jiayin Yang^{1

4}

Affiliations

¹ Key Laboratory of Transplant Engineering and Immunology, Laboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Department of Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴ Department of General Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

^# Contributed equally.

Abstract

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.

Keywords: Mendelian randomization; T2D; cardiovascular disease; heart failure; serum uric acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiovascular Diseases* / etiology
Cardiovascular Diseases* / genetics
Cross-Sectional Studies
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / genetics
Genome-Wide Association Study
Heart Failure*
Humans
Mendelian Randomization Analysis
Nutrition Surveys
Uric Acid

Substances

Uric Acid

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (No. 82070674 to JY); the Postdoctoral Research Foundation of China (No. 2020M683315 to YH); and the “Post-Doctor Research Project”, West China Hospital, Sichuan University (No. 2020HXBH070 to YH).