Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study

Shen, Rui; Pan, Chengliang; Yi, Guiwen; Li, Zhiyang; Dong, Chen; Yu, Jian; Zhang, Jiangmei; Dong, Qian; Yu, Kunwu; Zeng, Qiutang

doi:10.3390/metabo14070385

Open AccessArticle

Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study

by

Rui Shen

^1,2,3,†,

Chengliang Pan

^1,2,3,†,

Guiwen Yi

^1,2,3,

Zhiyang Li

^1,2,3,

Chen Dong

^1,2,3,

Jian Yu

^1,2,3,

Jiangmei Zhang

^1,2,3,

Qian Dong

^1,2,3,

Kunwu Yu

^1,2,3,*

and

Qiutang Zeng

^1,2,3,*

¹

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

²

Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

³

Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Metabolites 2024, 14(7), 385; https://doi.org/10.3390/metabo14070385

Submission received: 4 May 2024 / Revised: 26 June 2024 / Accepted: 10 July 2024 / Published: 13 July 2024

(This article belongs to the Special Issue Metabolism in Diabetes Progression and Diabetic Complications)

Download

Browse Figures

Versions Notes

Abstract

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096–1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07–11.99%), the fatty acid group (4.78–12.82%), and the cholesterol group (3.64–11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D.

Keywords: type 2 diabetes; calcific aortic valve stenosis; mediation; Mendelian randomization; metabolites; blood pressure

Share and Cite

MDPI and ACS Style

Shen, R.; Pan, C.; Yi, G.; Li, Z.; Dong, C.; Yu, J.; Zhang, J.; Dong, Q.; Yu, K.; Zeng, Q. Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study. Metabolites 2024, 14, 385. https://doi.org/10.3390/metabo14070385

AMA Style

Shen R, Pan C, Yi G, Li Z, Dong C, Yu J, Zhang J, Dong Q, Yu K, Zeng Q. Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study. Metabolites. 2024; 14(7):385. https://doi.org/10.3390/metabo14070385

Chicago/Turabian Style

Shen, Rui, Chengliang Pan, Guiwen Yi, Zhiyang Li, Chen Dong, Jian Yu, Jiangmei Zhang, Qian Dong, Kunwu Yu, and Qiutang Zeng. 2024. "Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study" Metabolites 14, no. 7: 385. https://doi.org/10.3390/metabo14070385

APA Style

Shen, R., Pan, C., Yi, G., Li, Z., Dong, C., Yu, J., Zhang, J., Dong, Q., Yu, K., & Zeng, Q. (2024). Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study. Metabolites, 14(7), 385. https://doi.org/10.3390/metabo14070385

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI