Sun Yanli, Deng Wei, Wang Heng, Chen Mingwei
Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of General Practice, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Front Neurol. 2025 Jul 8;16:1580862. doi: 10.3389/fneur.2025.1580862. eCollection 2025.
Insulin resistance (IR) has been linked to poor stroke prognosis even in non-diabetic patients, but the underlying mechanisms remain unclear. This study aims to explore whether the association between IR and poor prognosis in non-diabetic patients with acute ischemic stroke (AIS) treated with intravenous recombinant tissue-type plasminogen activator (IV-rtPA) is mediated by systemic inflammation.
In this retrospective study, 841 consecutive patients with AIS but without a history of diabetes treated with IV-rtPA were included. IR was evaluated by means of the triglyceride-glucose index (TyG). Inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and inflammation prognostic index (IPI), were calculated based on blood parameters obtained within 24 h of admission. The primary outcome was poor prognosis at 90 days [modified Rankin Scale (mRS) score ≥3]. Multivariable logistic regression analysis was performed to explore the associations among TyG, inflammatory markers, and the poor prognosis. A mediation analysis was performed to examine the relationship between IR and the study outcome mediated by systemic inflammation.
In total, 107 (12.72%) had poor prognosis. After adjusting for confounders (Model 3), multivariable logistic regression analysis revealed that both TyG and NLR were significantly associated with poor prognosis [odds ratio (OR), 2.212 (95% CI, 1.564-5.617), < 0.001; 1.059 (95% CI, 0.904-1.241), = 0.004; respectively]. Both indicators exhibited strong predictive value for poor prognosis, with areas under the curve (AUCs) of 0.823 and 0.730, respectively. Moreover, NLR and IPI were found to partially mediate the relationship between TyG and poor prognosis, with mediation proportions of 16.5 and 13.8%, respectively. After propensity score matching (PSM), the mediating effects of inflammatory markers became more pronounced.
Our study found that insulin resistance was associated with poor prognosis in non-diabetic patients treated with IV-rtPA, and this association was partially mediated by NLR and IPI to a modest extent. These findings offer new insights into the clinical management of non-diabetic AIS patients after IV.
胰岛素抵抗（IR）与卒中预后不良相关，即使在非糖尿病患者中也是如此，但其潜在机制仍不清楚。本研究旨在探讨在接受静脉注射重组组织型纤溶酶原激活剂（IV-rtPA）治疗的急性缺血性卒中（AIS）非糖尿病患者中，IR与预后不良之间的关联是否由全身炎症介导。
在这项回顾性研究中，纳入了841例连续接受IV-rtPA治疗且无糖尿病病史的AIS患者。通过甘油三酯-葡萄糖指数（TyG）评估IR。根据入院后24小时内获得的血液参数计算炎症标志物，包括中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、全身免疫炎症指数（SII）和炎症预后指数（IPI）。主要结局是90天时预后不良[改良Rankin量表（mRS）评分≥3]。进行多变量逻辑回归分析以探讨TyG、炎症标志物与预后不良之间的关联。进行中介分析以检验IR与由全身炎症介导的研究结局之间的关系。
共有107例（占12.72%）患者预后不良。在调整混杂因素后（模型3），多变量逻辑回归分析显示TyG和NLR均与预后不良显著相关[比值比（OR）分别为2.212（95%置信区间，1.564-5.617），P<0.001；1.059（95%置信区间，0.904-1.241），P=0.004]。这两个指标对预后不良均具有较强的预测价值，曲线下面积（AUC）分别为0.823和0.730。此外发现NLR和IPI部分介导了TyG与预后不良之间的关系，中介比例分别为16.5%和13.8%。在倾向评分匹配（PSM）后，炎症标志物的中介作用更加明显。
我们的研究发现，在接受IV-rtPA治疗的非糖尿病患者中，胰岛素抵抗与预后不良相关，且这种关联在一定程度上部分由NLR和IPI介导。这些发现为IV治疗后非糖尿病AIS患者的临床管理提供了新的见解。
