Homocysteine and vascular disease in diabetes: a double hit?

M.S.P. Huijberts, A. Becker, C.D. Stehouwer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Cardiovascular disease is a major problem in diabetes, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinaemia, may be related to the development of cardiovascular complications in diabetic individuals. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. Homocysteine levels in diabetes are modulated by hyperfiltration and renal dysfunction, as well as low folate status. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinaemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration is a significant predictor of cardiovascular events and death. This relation seems to be stronger in subjects with diabetes than without. The underlying pathophysiological mechanism of this increased vascular risk remains unexplained, but may be related to worsening of endothelial dysfunction and/or structural vessel properties induced by oxidative stress. Because homocysteine and diabetes have apparent synergistic detrimental vascular effects, patients with diabetes are candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.
Original languageEnglish
Pages (from-to)993-1000
JournalClinical Chemistry and Laboratory Medicine
Issue number10
Publication statusPublished - 1 Jan 2005

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