BACKGROUND Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

中文翻译：

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2 型糖尿病与脊柱退行性疾病有关吗？：来自观察和 2 样本孟德尔随机化分析的证据。


背景 2 型糖尿病 （T2DM） 和脊髓退行性疾病 （SDD） 是经常共存的常见疾病。然而，传统的观察性研究和最近的孟德尔随机化 （MR） 研究都证明了关于 T2DM 和 SDD 之间关联的相互矛盾的证据。这项比较研究使用观察和 MR 分析探索和比较了 T2DM 和 SDD 之间的关联。方法 对于观察性分析，横断面研究（44,972 名 T2DM 参与者和 403,095 名非 T2DM 参与者）、病例对照研究（38,234 名 SDD 参与者和 409,833 名非 SDD 参与者）和前瞻性研究（35,550 名 T2DM 参与者和 392,046 名非 T2DM 参与者，随访信息至 2022 年）使用 2006 年至 2022 年英国生物样本库的个体水平数据来测试 T2DM 和 SDD 之间的关系。对于 MR 分析，使用来自英国生物银行的参与者数据获得的单核苷酸多态性与 SDD 易感性之间的关联，该生物银行从 2006 年到 2022 年有 407,938 名参与者，以及 FinnGen 联盟，从 2017 年到 2022 年有 2022 名参与者，以及使用涉及 1,407,282 人的汇总全基因组关联研究的汇总统计数据获得的 T2DM 遗传易感性被检查。T2DM 的发病和严重程度在所使用的数据库中不可用。结果 T2DM 参与者比同龄人更容易患 SDD。Logistic 回归分析确定 T2DM 是 SDD 的独立危险因素，Cox 比例风险模型结果证实了这一点。然而，使用单核苷酸多态性作为工具，MR 分析表明 T2DM 和 SDD 之间没有因果关系。 在敏感性分析中缺乏这种关联是稳健的，并且没有看到多效性。结论 我们的结果表明，T2DM 和 SDD 之间的关联可能依赖于方法。研究人员和临床医生在解释 T2DM 和 SDD 之间的关联，尤其是因果关系时应谨慎。我们的研究结果通过各种分析方法为 T2DM 和 SDD 之间的关联提供了新的见解，并指导未来有效预防和管理 T2DM 和 SDD 的研究和临床工作。证据级别 预后 III 级。有关证据级别的完整描述，请参阅作者说明。