Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, China.
Inflammopharmacology. 2024 Dec;32(6):3717-3728. doi: 10.1007/s10787-024-01542-8. Epub 2024 Aug 11.
The potential effects of insulin therapy on osteoarthritis (OA) risk are poorly understood. This study aimed to explore the causal relationship between insulin therapy and OA.
Mendelian randomization (MR) analysis was performed to examine the association between genetically proxied inhibition of insulin targets and the risk of overall, hip (HOA) and knee OA (KOA). We then performed univariable MR using summary statistics regarding insulin target genes derived from the DrugBank database. Data related to blood glucose reduction levels were used as a proxy for insulin levels. Two phenotypes, type 2 diabetes, and glycosylated hemoglobin levels, were selected as positive controls to confirm the direction and validity of the proxies. The OA datasets were derived from the UK Biobank cohort. Multivariable MR was adjusted for body mass index, sedentary behavior, cigarette smoking, frequency of alcohol intake, age, and genetic sex.
Genetically proxied insulin therapy was associated with an increased risk of overall OA [odds ratio (OR):1.2595; 95% confidence interval (CI):1.0810-1.4675] and HOA (OR:1.4218; 95%CI:1.1240-1.7985), which remained consistent across multiple MR methods. After adjusting for confounders, we found evidence supporting a significant causal link with a higher risk of overall OA and HOA. A further two-step MR analysis revealed no significant mediation effects from the six mediators in the associations.
There was a causal association between genetically proxied insulin therapy and a higher risk of OA, especially HOA.
胰岛素治疗对骨关节炎（OA）风险的潜在影响尚未得到充分了解。本研究旨在探讨胰岛素治疗与 OA 之间的因果关系。
采用孟德尔随机化（MR）分析方法，研究胰岛素靶基因抑制与全因、髋关节（HOA）和膝关节 OA（KOA）风险之间的关联。然后，我们使用来自 DrugBank 数据库的胰岛素靶基因汇总统计数据进行单变量 MR。血糖降低水平的数据被用作胰岛素水平的替代指标。选择 2 型糖尿病和糖化血红蛋白水平作为阳性对照，以确认替代指标的方向和有效性。OA 数据集来源于 UK Biobank 队列。多变量 MR 调整了体重指数、久坐行为、吸烟、饮酒频率、年龄和遗传性别。
基因上代理的胰岛素治疗与全因 OA（比值比 [OR]：1.2595；95%置信区间 [CI]：1.0810-1.4675）和 HOA（OR：1.4218；95%CI：1.1240-1.7985）风险增加相关，这在多种 MR 方法中均保持一致。在调整混杂因素后，我们发现有证据支持与全因 OA 和 HOA 风险增加之间存在显著的因果关系。进一步的两步 MR 分析表明，在这些关联中，六个中介物没有显著的中介效应。
基因上代理的胰岛素治疗与 OA 风险增加之间存在因果关系，尤其是 HOA。
