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. 2023 Sep;123(9):913-919.
doi: 10.1055/a-2040-4850. Epub 2023 Feb 22.

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

Song Hu  1 , Jiang-Shan Tan  1 , Meng-Jin Hu  2 , Ting-Ting Guo  1 , Liyuan Chen  1 , Lu Hua  1 , Jian Cao  3
Affiliations

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

Song Hu et al. Thromb Haemost. 2023 Sep.

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.

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Conflict of interest statement

None declared.

Figures

Fig. 1
Fig. 1
The causal association of diabetes with VTE. In univariable MR analysis, results of IVW-MRE suggested that there were no significant causal effects of type 1 ( A ) and type 2 ( B ) diabetes on VTE. CI, confidence interval; DVT, deep vein thrombosis; IVW-MRE, inverse variance weighting with multiplicative random effect method; MR, Mendelian randomization; No. SNPs, number of single-nucleotide polymorphisms; OR, odds ratio; PE, pulmonary embolism; VTE, venous thromboembolism.
Fig. 2
Fig. 2
The causal associations of VTE with type 1 and type 2 diabetes. The results showed that there were no causal effects of VTE ( A ), DVT ( B ), and PE ( C ) on type 1 and type 2 diabetes by IVW-MRE in univariable MR analysis. CI, confidence interval; DVT, deep vein thrombosis; IVW-MRE, inverse variance weighting with multiplicative random effect method; MR, Mendelian randomization; No. SNPs, number of single-nucleotide polymorphisms; OR, odds ratio; PE, pulmonary embolism; VTE, venous thromboembolism.
See this image and copyright information in PMC

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