The causal association between type 2 diabetes and spinal stenosis: A Mendelian randomization analysis

Spinal stenosis is a prevalent degenerative spinal disease and one of the main causes of pain and dysfunction in older adults. Substantial evidence indicates a potentially relevant association between type 2 diabetes mellitus (T2DM) and spinal stenosis. However, the causality between these 2 disorders remains unclear. Therefore, we intended to elucidate this relationship using Mendelian Randomization (MR) analysis in this study. Based on genome-wide association study (GWAS) data on T2DM and spinal stenosis, we performed a bidirectional 2-sample MR analysis to evaluate the causality of T2DM and spinal stenosis. We assessed heterogeneity using Cochran's Q statistic and horizontal pleiotropy using the MR-Egger-intercept. "Leave-one-out" analysis was performed to determine the reliability of causal relationships. In addition, we conducted multivariate MR to clarify the direct influence of T2DM on spinal stenosis after accounting for the effect of body mass index (BMI) on spinal stenosis. Our results indicated that Individuals with T2DM had a heightened risk of spinal stenosis (odds ratio [OR]: 1.050; 95% CI: 1.004-1.098, P = .031). Moreover, no reverse causality existed between T2DM and spinal stenosis. The results of the sensitivity analysis suggest that causality is steady and robust. Multivariate MR results demonstrated that the causality of T2DM on spinal stenosis was not related to BMI (OR, 1.047; 95% CI: 1.003-1.093; P = .032). MR analyses demonstrated a possible positive causal relationship between T2DM and spinal stenosis and that this causality was unrelated to BMI.