Nonlinear Association Between Serum Uric Acid and Incident Stroke in Patients with Diabetes: A Two-Centre Cohort Study.

Background: Serum uric acid (SUA) has been linked to vascular injury, but its impact on stroke risk in diabetic patients-a population inherently prone to cerebrovascular events-remains uncertain, and whether a threshold effect exists is unclear. Methods: We included 3718 diabetic patients from two clinical centers. Multivariable-adjusted Cox proportional hazards models with stepwise covariate adjustment were used to assess associations between SUA and overall stroke and its subtypes. Kaplan-Meier curves estimated cumulative incidence across SUA quartiles. Restricted cubic spline regression examined dose-response relationships and potential threshold effects, and sex-stratified analyses were also performed. Results: Elevated SUA was significantly associated with increased risks of stroke and subtypes. The highest SUA quartile showed a significantly higher cumulative risk. RCS revealed threshold effects: risks of stroke, ischemic stroke, and hemorrhagic stroke increased when SUA exceeded 335, 330, and 340 μmol/L, respectively. Sex-stratified analyses yielded consistent findings, with thresholds at 335 μmol/L for males and 350 μmol/L for females. Conclusion: In conclusion, this observational study confirms a significant association between SUA and stroke risk in diabetic patients with a threshold effect, suggesting potential clinical value for monitoring and urate-lowering therapy. However, sex-specific threshold findings should be interpreted cautiously as hypothesis-generating, and prospective randomized controlled trials are needed for validation.