Homocysteine levels are associated with the severity of peripheral arterial disease in Type 2 diabetic patients

Background: Homocysteine levels are positively associated with the risk of cardiovascular disease. They might be determined by both MTHFR677C-->T polymorphisms and folate or B-vitamin status. Objectives: To investigate the possible association between plasma homocysteine levels and its genetic or environmental determinants and either the presence or the severity of peripheral arterial disease (PAD), in Type 2 diabetic patients. Methods: From a cohort of 944 patients with Type 2 diabetes, 135 patients with PAD were selected, and frequency-matched for age and sex with 219 Type 2 diabetic control patients without macrovascular complications. According to the increasing severity of the disease, patients were divided into PAD(1) (only diffuse calcifications of the arteries without any stenosis or occlusion), PAD(2) (one or two stenosis or occlusions) and PAD(3) (three or more). Results: Homocysteine levels were similar in control and case patients (10.3 mumol L-1 vs. 10.7 mumol L-1, P = 0.53); however, a significant increase was found in PAD(3) patients: odds ratio = 2.77 (95% confidence interval 1.14, 6.72) for patients with homocysteine levels above the median vs. those under the median in multivariate analysis. Although all significantly associated with homocysteine levels, neither MTHFR genotype nor folic acid or vitamin B-12 levels were associated with severity of PAD. A significant interaction (P < 0.05) was found between folic acid and MTHFR polymorphism in determining the levels of homocysteine. Conclusions: In Type 2 diabetes, homocysteine was associated with the angiographic severity of PAD, but neither the genotypes nor vitamin levels contributed to this association.