Diabetes-duration-related shifts in inflammation-resolving lipid mediator signatures and their association with 3-month functional outcome in large artery atherosclerotic stroke.

BACKGROUND

Specialized pro-resolving lipid mediators are involved in post-stroke neuroinflammation, but their relevance in large artery atherosclerotic (LAA) stroke, particularly in relation to diabetes duration, remains unclear.

METHODS

In this single-center retrospective study, 175 patients with LAA stroke were enrolled. Serum lipoxin A4 (LXA4), leukotriene B4 (LTB4), and resolvin D2 (RvD2) were measured within 72 h of stroke onset. Functional outcome at 3 months was assessed using the modified Rankin Scale. Analyses were stratified by type 2 diabetes mellitus (T2DM) status and diabetes duration (<5 vs. ≥5 years). Logistic regression and linear support vector machine models were used in exploratory analyses.

RESULTS

Of the 175 patients, 130 had a favorable outcome and 45 a poor outcome. LXA4 levels were higher in the favorable-outcome group, although the difference was not significant. No significant differences in LXA4, LTB4, or RvD2 were observed between patients with and without T2DM. In contrast, within the T2DM subgroup, patients with a diabetes duration of ≥5 years showed higher LXA4 and LTB4 levels and a lower RvD2/LTB4 ratio than those with a duration of <5 years. Diabetes duration correlated positively with both LXA4 and LTB4. In exploratory machine learning analyses, LXA4 was consistently retained, and model performance declined after its removal.

CONCLUSION

These findings are exploratory. LAA stroke was associated with diabetes duration-related remodeling of specialized pro-resolving lipid mediator profiles. Compared with diabetes status alone, diabetes duration may better reflect metabolic-inflammatory heterogeneity. These findings are exploratory; LXA4 did not demonstrate a statistically significant association with functional outcome, and no independent prognostic value has been established. LXA4 may represent a candidate signaling molecule warranting further investigation.