Mendelian randomization study on the causal relationship between type 2 diabetes and osteoporosis
10.3760/cma.j.cn112138-20241108-00743
- VernacularTitle:2型糖尿病与骨质疏松因果关系的孟德尔随机化研究
- Author:
Han YU
1
;
Zongbao LI
;
Fan HU
;
Nan LI
;
Yanhui LU
;
Chunlin LI
Author Information
1. 解放军总医院第二医学中心内分泌科 国家老年疾病临床研究中心，北京 100853
- Publication Type:Journal Article
- Keywords:
Diabetes mellitus, type 2;
Osteoporosis;
Waist-hip ratio;
Paradox;
Mendelian randomization study
- From:
Chinese Journal of Internal Medicine
2025;64(3):225-233
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the causal relationship between type 2 diabetes and lumbar bone mineral density and spinal fractures and to further explore the impact of central obesity on the diabetic bone paradox.Methods:A Mendelian randomization (MR) study was implemented. Single nucleotide polymorphisms (SNPs) associated with type 2 diabetes were selected from the data of genome-wide association studies as instrumental variables, with lumbar bone density and spinal fractures as the outcome variables. The inverse variance weighting method, weighted median method, and MR-Egger regression were applied to identify a causal relationship between type 2 diabetes and osteoporosis at the genetic level. Additionally, to analyze the impact of central obesity in the diabetic bone paradox, the waist-to-hip ratio was introduced as a new exposure variable, with type 2 diabetes and lumbar bone density as outcome variables, and the MR method was applied again to uncover the influencing factors.Results:The screening criteria were based on the three main assumptions of MR. Finally, 62 SNPs for type 2 diabetes and 241 SNPs for waist-to-hip ratio were included in the MR analysis. Using inverse variance weighting as the primary analysis, the causal association effect analysis indicated a causal relationship between type 2 diabetes and increased lumbar bone density ( OR=1.047 6, P=0.007) and spinal fractures ( OR=1.000 9, P=0.014). A causal relationship between waist-to-hip ratio and type 2 diabetes ( OR=1.638 6, P<0.001) was identified, indicating that the waist-to-hip ratio was a risk factor for type 2 diabetes and may have a causal association with increased lumbar bone density ( OR=1.096 3, P=0.044). This suggests that the waist-to-hip ratio may indirectly affect the relationship between diabetes and osteoporosis. The MR-Egger intercept test showed no horizontal pleiotropy in this study. The leave-one-out analysis indicated that no single SNP had a significant impact on the overall results. Furthermore, the MR-pleiotropy residual sum and outlier (MR-PRESSO) test results did not detect any outlier SNPs. Conclusion:MR analysis identified a causal relationship between type 2 diabetes and increased lumbar bone density as well as a higher risk of spinal fractures, a paradox that may be related to central obesity.
