Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
The Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China.
J Diabetes. 2023 Nov;15(11):987-993. doi: 10.1111/1753-0407.13451. Epub 2023 Jul 31.
Physical inactivity is an independent risk factor for type 2 diabetes (T2D). Osteoarthritis (OA) is a common joint disease that limits patients' physical activity, which may increase risk of other chronic diseases including T2D. However, studies evaluating the effect of OA on T2D are scarce. This study aimed to investigate the causal effect of knee and hip OA on risk of T2D from a genetic perspective.
We performed two-sample Mendelian randomization (MR) analyses to obtain nonconfounding estimates of the effect of OA on T2D risk. Single nucleotide polymorphisms (SNPs) from genome-wide association studies were selected as genetic instruments for radiographic knee and hip OA (ie, Kellgren-Lawrence grade ≥2). The associations of these SNPs with T2D were evaluated in participants from the UK Biobank. Sensitivity analyses were conducted to test the robustness of the MR results.
Genetic predisposition of knee but not hip OA was significantly associated with an increased risk of T2D (knee OA: odds ratio [OR] 1.18, 95% confidence interval (CI) 1.09-1.27, p <.001; hip OA: OR 1.04, 95% CI 0.94-1.16, p = .425). Sensitivity analyses showed that the main findings are robust.
The current study provides genetic evidence supporting that knee OA is a potential risk factor for T2D.
身体活动不足是 2 型糖尿病（T2D）的一个独立危险因素。骨关节炎（OA）是一种常见的关节疾病，限制了患者的身体活动，这可能会增加包括 T2D 在内的其他慢性疾病的风险。然而，评估 OA 对 T2D 影响的研究很少。本研究旨在从遗传角度探讨膝关节和髋关节 OA 对 T2D 风险的因果效应。
我们进行了两样本 Mendelian 随机化（MR）分析，以获得 OA 对 T2D 风险影响的非混杂估计值。全基因组关联研究中的单核苷酸多态性（SNP）被选为放射学膝关节和髋关节 OA（即 Kellgren-Lawrence 分级≥2）的遗传工具。这些 SNP 与 T2D 的关联在英国生物库的参与者中进行了评估。进行敏感性分析以检验 MR 结果的稳健性。
膝关节而非髋关节 OA 的遗传易感性与 T2D 风险增加显著相关（膝关节 OA：优势比 [OR] 1.18，95%置信区间 [CI] 1.09-1.27，p<.001；髋关节 OA：OR 1.04，95% CI 0.94-1.16，p=0.425）。敏感性分析表明，主要发现是稳健的。
本研究提供了遗传证据，支持膝关节 OA 是 T2D 的一个潜在危险因素。
