Association between homocysteine and severe cerebral small vessel disease burden in patients with type 2 diabetes mellitus

Objective Cerebral small vessel disease (CSVD) is one of the common complications in patients with type 2 diabetes mellitus (T2DM). Homocysteine (Hcy), an emerging biomarker, has an unclear relationship with the CSVD burden in T2DM patients. This study aims to investigate the association between Hcy levels and the burden of severe CSVD in diabetic patients. Methods A total of 236 patients with T2DM were enrolled in this study. Based on the total CSVD burden score, patients were divided into a mild CSVD burden group (score ≤ 2, n=181) and a severe CSVD burden group (score > 2, n=55). Multivariable logistic regression models were used to evaluate the association between Hcy levels and severe CSVD burden in T2DM patients. Restricted cubic spline (RCS) analyses were conducted to explore the nonlinear relationship between Hcy and the risk of severe CSVD burden. Subgroup analyses and interaction tests were performed to assess potential differences across groups. Results Multivariable logistic regression analysis demonstrated that higher Hcy levels were independently associated with an increased risk of severe CSVD burden (OR = 1.13, 95% CI: 1.04–1.23). RCS analysis indicated a positive linear relationship between Hcy levels and the risk of severe CSVD burden. Subgroup analyses showed that this association remained significant in patients with BMI < 25 kg/m 2 , age ≥ 60 years, diabetes duration < 10 years, regardless of HbA1c levels, with or without hypertension, and in those without coronary artery disease or diabetic retinopathy. Moreover, a significant interaction was observed between BMI and the relationship between Hcy and severe CSVD burden (P for interaction = 0.020). The association was particularly pronounced in the BMI < 25 kg/m 2 subgroup (OR = 1.26, 95% CI: 1.08–1.46). Conclusion Elevated serum Hcy is independently associated with a higher burden of severe CSVD in patients with T2DM. Monitoring and managing Hcy levels may have potential value for identifying patients at greater risk of CSVD progression.