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CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(09): 913-919
DOI: 10.1055/a-2040-4850
Stroke, Systemic or Venous Thromboembolism

The Causality between Diabetes and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study

Song Hu
1   Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Jiang-Shan Tan
1   Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Meng-Jin Hu
2   State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Fuwai Hospital, Beijing, China
,
Ting-Ting Guo
1   Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Liyuan Chen
1   Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Lu Hua
1   Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Jian Cao
3   Department of Cardiology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
› Author Affiliations
Funding The study was supported by grants from CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-040) and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences (NCRC2020007).
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Abstract

Background Diabetes was considered as a risk factor for venous thromboembolism (VTE), but conflicting findings have been reported from observational studies. This study aimed at investigating the causal associations of type 1 and type 2 diabetes with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods We designed a bidirectional two-sample Mendelian randomization (MR) analysis by using summary-level data from large genome-wide association studies performed in European individuals. Inverse variance weighting with multiplicative random effect method was used to obtain the primary causal estimates, and weighted median, weighted mode, and MR egger regression were replenished as sensitivity analyses to test the robustness of the results.

Results We found no significant causal effects of type 1 diabetes on VTE (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96–1.00, p = 0.043), DVT (OR: 0.98, 95% CI: 0.95–1.00, p = 0.102), and PE (OR: 0.98, 95% CI: 0.96–1.01, p = 0.160). Similarly, no significant associations of type 2 diabetes with VTE (OR: 0.97, 95% CI: 0.91–1.03, p = 0.291), DVT (OR: 0.96, 95% CI: 0.89–1.03, p = 0.255), and PE (OR: 0.97, 95% CI: 0.90–1.04, p = 0.358) were also observed. Results from multivariable MR analysis were consistent with the findings in univariable analysis. In the other direction, the results showed no significant causal effects of VTE on type 1 and type 2 diabetes.

Conclusion This MR analysis demonstrated no significant causal associations of type 1 and type 2 diabetes with VTE in both directions, in conflict with previous observational studies reporting positive association, which provided clues for understanding the underlying pathogenesis of diabetes and VTE.

Keywords

diabetes - venous thromboembolism - deep vein thrombosis - pulmonary embolism - Mendelian randomization

Supplementary Material



Publication History

Received: 01 November 2022

Accepted: 31 January 2023

Accepted Manuscript online:
22 February 2023

Article published online:
09 March 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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