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

Abstract

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.