ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Clinical Diabetes
This article is part of the Research TopicAssociation of Diabetes Mellitus with Cognitive Impairment and Neurological Disorders Vol. 2View all 14 articles
Association Between Homocysteine and Severe Cerebral Small Vessel Disease Burden in Patients with Type 2 Diabetes Mellitus
Provisionally accepted
Wensheng HuangHuijuan JieJinsheng YiQingchang LiuSimin LiYingying LuoShutong TangZelin Chi
Changquan Wu*- The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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/m² 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.
Keywords: Body Mass Index, cerebral small vessel disease burden, Homocysteine, microvascular, type 2 diabetes mellitus
Received: 04 Jun 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Huang, Jie, Yi, Liu, Li, Luo, Tang, Chi and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Changquan Wu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.