Plasma homocysteine thiolactone associated with risk of macrovasculopathy in Chinese patients with type 2 diabetes mellitus

Abstract

This study investigated the role of homocysteine thiolactone (HcyT) in the development of macrovascular complications in Chinese patients with type 2 diabetes. HcyT has been proposed as a possible molecular basis for homocysteine (Hcy)-induced vascular damage. One hundred and sixty subjects were recruited into this study: 40 healthy controls and 120 patients with type 2 diabetes. Plasma Hcy levels were measured by polarization immunoassay and HcyT concentrations were monitored using high-performance liquid chromatography on a reversephase C18 column with ultraviolet detection. Plasma folic acid and vitamin B(12) levels were measured using radioimmunoassay methods. Plasma Hcy and HcyT concentrations in patients with type 2 diabetes were significantly higher than in healthy controls (Hcy [25th and 75th quartiles]: 9.28 [7.51-11.82] vs. 5.64 [5.17-8.00] micromol/L, P=0.01; HcyT: 3.38 [2.94-4.73] vs. 2.91 [2.77-3.08] nmol/L, P<0.05). Plasma Hcy and HcyT levels in patients with macrovasculopathy (MAVP) were significantly higher compared with patients without MAVP (Hcy: 10.36 [7.67-12.45] vs. 7.85 [6.76-10.52] micromol/L, P<0.05; HcyT: 4.27 [3.02-5.11] vs. 3.12 [2.63-3.77] nmol/L, P<0.05). Plasma HcyT concentrations were positively correlated with urinary excretion of albumin/creatinine (Alb/Cr; r=0.285, P=0.007), duration of diabetes (r=0.249, P=0.019), age (r=0.233, P=0.028), and fibrinogen levels (r=0.289, P=0.034). Plasma HcyT concentrations were negatively correlated with high-density lipoprotein levels (r=-0.223, P=0.037). Binary logistic regression showed that HcyT, Hcy, smoking, serum triglyceride, and urine Alb/Cr were significantly associated with the risk of diabetic MAVP (P<0.05). Hcy and HcyT levels were associated with the development and progression of diabetic MAVP. HcyT may provide a plausible chemical mechanism for explaining Hcy toxicity in the human vascular endothelium.