Review: Homocysteine, endothelial dysfunction and oxidative stress in type 1 diabetes mellitus

Type 1 diabetes is associated with an increased risk of cardiovascular disease, which cannot be fully explained by traditional risk factors. Elevated plasma homocysteine is an independent risk factor for macrovascular disease in the general population. This review examines the evidence for hyperhomocysteinaemia in patients with type 1 diabetes and describes the mechanisms that may lead to increased macrovascular susceptibility. While reports of plasma homocysteine levels in type 1 diabetes are inconsistent, increased plasma homocysteine levels have been found in subgroups of patients with microalbuminuria, nephropathy and macrovascular disease. Although a direct causal relationship between plasma homocysteine and atherosclerosis remains to be proven, potential mechanisms of vascular damage by homocysteine include endothelial dysfunction linked to increased oxidative stress. This could contribute to the association between hyperhomocysteinaemia and macrovascular disease in type 1 diabetes.