Associations of the triglyceride-glucose index and intracranial arterial stenosis with poor functional outcome after ischemic stroke: a retrospective observational study of 712 patients

Background: While intracranial atherosclerosis (ICAS) and insulin resistance (IR) often co-occur in ischemic stroke, their combined prognostic impact is unclear; we hypothesized their synergy predisposes to worse short-term outcomes. Methods: We conducted a retrospective analysis of 712 consecutive patients with acute ischemic stroke. The primary outcome was poor functional status, defined as modified Rankin Scale score > 2 at 90 days. Participants were categorized according to TyG index (as a surrogate for IR) and ICAS status. Subsequent stratification based on ICAS severity (none, moderate, severe) and number of affected vessels (none, single, multiple) enabled dose-response evaluation. Subgroup analyses and interaction analyses were further performed to assess the robustness of the associations and explore potential interactive effects between TyG index and ICAS. Exploratory mediation analysis quantified the proportion of ICAS's total statistical effect on functional outcomes that could be explained via the TyG index. Results: Univariate analysis demonstrated that both elevated TyG index (OR 1.34, 95% CI 1.01-1.79) and presence of ICAS (OR 1.74, 95% CI 1.19-2.56) were associated with poor outcomes. Although the combination of high TyG index and ICAS showed a non-significant trend (OR = 1.77, 95% CI: 0.98-3.17, p = 0.057), high TyG index significantly increased poor outcome risk in patients with severe ICAS (OR = 2.15, 95% CI: 1.13-4.09) or multiple ICAS lesions (OR = 2.11, 95% CI: 1.11-4.02). The exploratory mediation analysis showed that the mediated proportion of the TyG index in the association between ICAS and poor post-stroke functional outcome was approximately 9.0% (95% CI: -0.8% to 68.2%), and this mediated effect was not statistically significant. Conclusions: The combined assessment of the TyG index and ICAS burden shows promise for identifying stroke patients at high risk of poor prognosis.