[Mendelian randomization study on the causal relationship between type 2 diabetes and osteoporosis].

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.