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Causality between genetically predicted type 2 diabetes and ankle fracture risk: A 2-sample Mendelian randomization
Wenren Wu1, Zhiqing Chen, Binshan Zhang
1Orthopedics Department, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dong Guan, Guangdong Province, China.
Medicine
|February 6, 2026
Summary
Diabetes mellitus significantly increases the risk of ankle fractures. This study used Mendelian randomization to confirm the causal link, aiding early screening and treatment for both conditions.
Area of Science:
- Genetics
- Endocrinology
- Orthopedics
Background:
- Diabetes mellitus is linked to joint fracture development.
- Understanding the specific causal relationship between diabetes and ankle fractures is crucial for targeted interventions.
Purpose of the Study:
- To investigate the causal relationship between diabetes mellitus type 2 and ankle fractures using a 2-sample Mendelian randomization analysis.
- To provide evidence for improved screening and early treatment strategies.
Main Methods:
- Utilized pooled genome-wide association study data from large European cohorts for diabetes (655,666 individuals) and ankle fractures (460,340 individuals).
- Employed various Mendelian randomization techniques, including inverse variance weighting, MR-Egger, and weighted median analysis, with diabetes-associated loci as instrumental variables.
- Conducted sensitivity and reverse Mendelian randomization analyses to ensure result robustness.
Main Results:
- A significant causal relationship was identified between diabetes mellitus and an increased risk of ankle fractures (Inverse Variance Weighting: OR = 1.07, 95% CI = 1.01-1.32, P = 0.02).
- The findings were robust across different analytical methods and sensitivity analyses.
Conclusions:
- Diabetes mellitus is causally associated with a higher risk of ankle fractures.
- These findings support the integration of diabetes screening in ankle fracture patients and vice versa for early detection and management.
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