Huang Xiaxuan, Dong Peina, Xu Yixian, Ling Yitong, Tan Shanyuan, Bai Zihong, Shen Si, Lyu Jun, Wang Hao
Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
CNS Neurosci Ther. 2025 Jun;31(6):e70420. doi: 10.1111/cns.70420.
This study investigated the relationship between estimated glucose disposal rate (eGDR), a validated marker of insulin resistance, and stroke subtypes and poststroke outcomes. Despite eGDR's established role in predicting cardiovascular outcomes, its impact on stroke risk and prognosis has not been fully explored.
This study included 462,550 participants from the UK Biobank with eGDR assessments, and participants were stratified into three categories based on tertiles of eGDR. The primary outcomes were stroke and its subtypes (ischemic and hemorrhagic stroke). Cox proportional hazard models and restricted cubic spline regression were used to analyze associations between eGDR and outcomes. Secondary analyses investigated poststroke adverse events (depression, disability, epilepsy, and delirium). Mediation analyses were conducted to explore the underlying mechanisms driven by inflammatory markers, eGDR, and stroke.
During a median follow-up of 13.9 years, 12,325 stroke cases were recorded. Compared to the lowest eGDR tertile (< 6.525 mg/kg/min), individuals in the highest tertile (> 8.494 mg/kg/min) demonstrated a significantly reduced risk of stroke (HR = 0.53, 95% CI: 0.50-0.56), particularly ischemic stroke (HR = 0.53, 95% CI: 0.50-0.57). Higher eGDR levels were also associated with a decreased risk of poststroke adverse outcomes (HR = 0.83, 95% CI: 0.73-0.94), with similar risk estimates observed for depression, disability, epilepsy, and delirium. Furthermore, inflammatory markers partially mediated the relationship between eGDR and stroke risk.
Elevated eGDR levels were associated with decreased risks of stroke and poststroke adverse outcomes. These findings suggest improving insulin sensitivity, as reflected by higher eGDR, maybe a potential therapeutic target for stroke prevention or stroke rehabilitation.
本研究调查了估计葡萄糖处置率(eGDR,一种经过验证的胰岛素抵抗标志物)与中风亚型及中风后结局之间的关系。尽管eGDR在预测心血管结局方面已确立作用,但其对中风风险和预后的影响尚未得到充分探索。
本研究纳入了英国生物银行中462,550名有eGDR评估的参与者,并根据eGDR三分位数将参与者分为三类。主要结局为中风及其亚型(缺血性和出血性中风)。采用Cox比例风险模型和限制性立方样条回归分析eGDR与结局之间的关联。二级分析调查了中风后不良事件(抑郁、残疾、癫痫和谵妄)。进行中介分析以探索炎症标志物、eGDR和中风所驱动的潜在机制。
在中位随访13.9年期间,记录了12,325例中风病例。与最低eGDR三分位数(<6.525mg/kg/min)相比,最高三分位数(>8.494mg/kg/min)的个体中风风险显著降低(HR = 0.53,95%CI:0.50 - 0.56),尤其是缺血性中风(HR = 0.53,95%CI:0.50 - 0.57)。较高的eGDR水平还与中风后不良结局风险降低相关(HR = 0.83,95%CI:0.73 - 0.94),抑郁、残疾、癫痫和谵妄的风险估计相似。此外,炎症标志物部分介导了eGDR与中风风险之间的关系。
eGDR水平升高与中风和中风后不良结局风险降低相关。这些发现表明,提高胰岛素敏感性(如较高的eGDR所反映的)可能是中风预防或中风康复的潜在治疗靶点。