It remains unclear whether an increased risk of type 2 diabetes (T2D) affects the risk of osteoarthritis (OA).

Here, we used two-sample Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on hip and knee OA. We identified single-nucleotide polymorphisms (SNPs) strongly associated with T2D, fasting glucose (FG), and 2-h postprandial glucose (2hGlu) from genome-wide association studies (GWAS). We used the MR inverse variance weighted (IVW), the MR–Egger method, the weighted median (WM), and the Robust Adjusted Profile Score (MR.RAPS) to reveal the associations of T2D, FG, and 2hGlu with hip and knee OA risks. Sensitivity analyses were also conducted to verify whether heterogeneity and pleiotropy can bias the MR results.

We did not find statistically significant causal effects of genetically increased T2D risk, FG, and 2hGlu on hip and knee OA (e.g., T2D and hip OA, MR–Egger OR = 1.1708, 95% CI 0.9469–1.4476, p = 0.1547). It was confirmed that horizontal pleiotropy was unlikely to bias the causality (e.g., T2D and hip OA, MR–Egger, intercept = −0.0105, p = 0.1367). No evidence of heterogeneity was found between the genetic variants (e.g., T2D and hip OA, MR–Egger Q = 30.1362, I² < 0.0001, p = 0.6104).

Our MR study did not support causal effects of a genetically increased T2D risk, FG, and 2hGlu on hip and knee OA risk.

目前尚不清楚 2 型糖尿病 (T2D) 的风险增加是否会影响骨关节炎 (OA) 的风险。

在这里，我们使用两样本孟德尔随机化 (MR) 来获得 T2D 和血糖特征对髋关节和膝关节 OA 影响的非混杂估计。我们从全基因组关联研究 (GWAS) 中鉴定出与 T2D、空腹血糖 (FG) 和餐后 2 小时血糖 (2hGlu) 密切相关的单核苷酸多态性 (SNP)。我们使用 MR 逆方差加权 (IVW)、MR-Egger 方法、加权中位数 (WM) 和稳健调整轮廓评分 (MR.RAPS) 来揭示 T2D、FG 和 2hGlu 与髋关节和膝关节的关联OA 风险。还进行了敏感性分析以验证异质性和多效性是否会影响 MR 结果。

我们没有发现遗传性增加的 T2D 风险、FG 和 2hGlu 对髋关节和膝关节 OA 的显着因果影响（例如，T2D 和髋关节 OA，MR-Egger OR = 1.1708，95% CI 0.9469–1.4476，p= 0.1547）。已证实水平多效性不太可能影响因果关系（例如，T2D 和髋关节 OA，MR-Egger，截距 = -0.0105，p= 0.1367）。在遗传变异（例如，T2D 和髋关节 OA、MR-Egger问= 30.1362,一世² < 0.0001,p= 0.6104)。

我们的 MR 研究不支持遗传性增加的 T2D 风险、FG 和 2hGlu 对髋关节和膝关节 OA 风险的因果影响。