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

<b>Objective:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 (<i>OR</i>=1.047 6, <i>P</i>=0.007) and spinal fractures (<i>OR</i>=1.000 9, <i>P</i>=0.014). A causal relationship between waist-to-hip ratio and type 2 diabetes (<i>OR</i>=1.638 6, <i>P</i><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 (<i>OR=</i>1.096 3, <i>P</i>=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. <b>Conclusion:</b> 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.