Tang Hanming, Zhao Jie, Yan Xuexu, Zheng Zhiyong, Bai Wenzhe, Tang Zhikun, Liu Xiaochen
College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250014, People's Republic of China.
Department of Osteoarthropathy, Affiliated Hospital of Shandong Traditional Chinese Medicine University, Jinan, Shandong Province, 250014, People's Republic of China.
J Multidiscip Healthc. 2025 Aug 9;18:4933-4945. doi: 10.2147/JMDH.S529217. eCollection 2025.
BACKGROUND: Evidence from prior research indicates a connection between orthopedic diseases and metabolic disorders, including type 2 diabetes (T2D), insulin resistance, and abdominal obesity. However, the causal relationships remain uncertain. This study utilized Mendelian randomization (MR) to investigate the causal effects of abdominal obesity, T2D, and fasting insulin (FI) on cervical disc disorders, osteoporosis (OP), and rheumatoid arthritis (RA). METHODS: Exposure data were sourced from genome-wide association studies (GWAS) for waist-hip ratio (WHR), body mass index (BMI), FI, and T2D with a sample size of 697,734 participants for WHR, 151,013 for BMI, and 62,892 cases with 596,424 controls for FI and T2D. Outcome data were derived from FinnGen, including cervical disc disorders (14,670 cases and 294,770 controls), OP (8,017 cases and 391,037 controls), and RA (13,621 cases and 262,844 controls). Univariate Mendelian randomization (UVMR) was performed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Multivariate Mendelian randomization (MVMR) included BMI as an adjustment. Sensitivity analyses incorporated Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis. RESULTS: UVMR identified WHR as a risk factor for cervical disc disorders (odds ratio [OR] = 1.147) and RA (OR = 1.260). FI increased the risk of cervical disc disorders (OR = 1.534), while T2D elevated the risk of RA (OR = 1.260) but lowered the risk of OP (OR = 0.925). MVMR confirmed FI's positive association with cervical disc disorders (OR = 1.716), T2D's increased risk for RA (OR = 1.062), and its protective role against OP (OR = 0.912). WHR remained a significant risk factor for RA (OR = 1.203). CONCLUSION: Genetically predicted WHR and T2D were associated with an increased risk of RA. Additionally, T2D and FI increased the risk of cervical disc disorders, while T2D was found to have a protective role against OP. These findings provide novel insights into the interplay between metabolic factors and prevalent orthopedic conditions, offering valuable implications for clinical decision-making and targeted disease management strategies.
背景：先前研究的证据表明，骨科疾病与代谢紊乱之间存在联系，包括2型糖尿病（T2D）、胰岛素抵抗和腹部肥胖。然而，因果关系仍不确定。本研究利用孟德尔随机化（MR）来研究腹部肥胖、T2D和空腹胰岛素（FI）对颈椎间盘疾病、骨质疏松症（OP）和类风湿性关节炎（RA）的因果效应。 方法：暴露数据来自全基因组关联研究（GWAS），涉及腰臀比（WHR）、体重指数（BMI）、FI和T2D，WHR的样本量为697,734名参与者，BMI为151,013名，FI和T2D的病例为62,892例，对照为596,424例。结局数据来自芬兰基因研究，包括颈椎间盘疾病（14,670例病例和294,770例对照）、OP（8,017例病例和391,037例对照）和RA（13,621例病例和262,844例对照）。使用逆方差加权（IVW）、MR-Egger和加权中位数方法进行单变量孟德尔随机化（UVMR）。多变量孟德尔随机化（MVMR）包括将BMI作为调整因素。敏感性分析纳入了Cochran's Q检验、MR-Egger截距检验和留一法分析。 结果：UVMR确定WHR是颈椎间盘疾病（优势比[OR]=1.147）和RA（OR=1.260）的危险因素。FI增加了颈椎间盘疾病的风险（OR=1.534），而T2D增加了RA的风险（OR=1.
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