Association between oxidative stress-related IGF-1 and prognosis after ischemic stroke: a systematic review and meta-analysis

Xinyu Liu¹Jun Wang²Congcong Wang^3*

• ¹Department of Endocrinology Jinhua People's Hospital 267 Danxi East Road, Jinhua City, Zhejiang Province, China. 321000, Jinhua, Zhejiang Province, China
• ²Department of Orthopedics, Rehabilitation hospital affiliated to National Research Center for Rehabilitation Technical Aids .Beijing, China. 100176, Beijing, China
• ³Department of Joint Surgery, Weifang People's Hospital, Shandong Second Medical University Weifang, Shandong, China. 261000, Weifang, China

Background and Purpose: Insulin-like growth factor-1 (IGF-1), an oxidative stress–related neurotrophic factor, has been investigated in stroke due to its potential roles in neuronal survival and vascular regulation. However, findings on its association with ischemic stroke and functional prognosis remain inconsistent. This review aimed to evaluate the association between circulating IGF-1 levels and (1) the risk of ischemic stroke and (2) post-stroke outcomes. Methods: We systematically searched EMBASE, MEDLINE, PubMed, Google Scholar, and the Cochrane Library from inception to June 2021, and updated the search to November 2025. Case-control or cohort studies reporting risks or odds ratios with 95% confidence intervals were included. Summary estimates were pooled using random-effects models when heterogeneity was substantial. Results: Our systematic literature search identified 10 articles. Four of these studies examined the association between IGF-1 and the risk of acute ischemic stroke, while the remaining six studies focused on the relationship between IGF-1 and unfavorable outcomes following acute ischemic stroke. No significant association was found between IGF-1 and ischemic stroke risk (risk ratio [RR] = 1.69, 95% confidence interval [CI] = 0.97 to 2.92, I² = 82.2%, random-effects model), nor was there a significant impact of IGF-1 on unfavorable outcomes after ischemic stroke (RR = 1.55, 95% CI = 0.89 to 2.68, I² = 86.6%, random-effects model). However, in the subgroup analysis of IGF-1's effect on unfavorable outcomes after ischemic stroke, IGF-1 was significantly associated with poor prognosis more than 1 year after stroke onset (RR = 3.33, 95% CI = 2.19 to 5.05, I² = 0%, random-effects model). Conclusions: This systematic review and meta-analysis suggests that oxidative stress-related IGF-1 may be associated with long-term unfavorable outcomes following ischemic stroke, particularly beyond 1 year after onset. However, no significant associations were found with the incidence of acute ischemic stroke or short-term outcomes. Given the observational nature of the included studies and inconsistencies in adjustment for confounders, these findings should be interpreted cautiously. IGF-1 may serve as a potential prognostic biomarker for long-term functional decline after stroke, but further large-scale prospective studies are needed to clarify causality and clinical applicability.