The mediation of systemic inflammation on insulin resistance and poor prognosis in non-diabetic ischemic stroke patients treated with intravenous thrombolysis.

Background and purpose: 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. Methods: 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. Results: 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), Conclusion: 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.