Background: 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.
Methods: 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.
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.
Conclusion: The current study provides genetic evidence supporting that knee OA is a potential risk factor for T2D.
背景:缺乏运动是2型糖尿病(T2D)的独立危险因素。骨关节炎(OA)是一种常见的关节疾病, 限制了患者的运动能力, 可能增加其他慢性疾病(包括T2D)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。 方法:我们进行了双样本孟德尔随机化(MR)分析, 以获得OA对T2D风险无偏估计的影响。我们从全基因组关联研究(GWAS)中选择了单核苷酸多态性(SNPs)作为放射学膝关节和髋关节OA(即Kellgren-Lawrence分级≥2)的遗传工具。然后评估这些SNPs与参与者来自英国生物库的T2D的关联性。进行敏感性分析以测试MR结果的稳健性。 结果:膝关节OA而非髋关节OA的遗传易感性显著增加T2D的风险(膝关节OA:优势比(OR)1.18, 95%置信区间(CI)1.09至1.27, p < 0.001, 髋关节OA:OR 1.04, 95% CI 0.94至1.16, p=0.425)。敏感性分析显示主要发现是稳健的。 结论:当前研究提供了遗传证据支持膝关节OA是T2D的潜在危险因素。.
Keywords: 2型糖尿病; Mendelian randomization; metabolites; osteoarthritis; type 2 diabetes; 代谢物; 孟德尔随机化; 骨关节炎.
© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.