Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes

Introduction: Homocysteine is a predictor of vascular disease and may have an important role in diabetes. In this study, we examined the effects of folic acid and methylcobalamin supplementation on changes in homocysteine (Hcy) levels and homocysteine thiolactonase/paraoxonase (HTase/PON) activity in a short-term trial. Methods: Ninety patients with type 2 diabetes were randomly divided into three groups: Group I received no vitamin supplementation, group II received 5 mg/day folic acid (orally), group III received folic acid (5 mg/day) in combination with methylcobalamin (500 mu g/day; intramuscularly, on prescription). All patients were treated for 2 weeks. Plasma Hcy, HTase/PON activity, vitamin B-12, and folic acid were measured before and after supplementation in each group. In addition, forty healthy (nondiabetic) controls were enrolled. Results: Serum HTase/PON activity was significantly higher in diabetics compared with controls, plasma Hcy levels were significantly lower (P < 0.05). After vitamin supplementation there was a significant reduction in plasma Hcy levels. The mean percentage reduction in Hcy was 2.75% in group I, 14% in group II and 37.3% in group III. There was a significant inverse correlation between the changes in HTase/PON activity and Hcy levels (r=-0.29, P=0.004). A 2.72% increase in HTase/PON activity was seen in group I, an 8.03% increase was detected when folic acid was given in group II (P < 0.001), and a 17.59% increase in HTase/PON activity was seen in group III (P < 0.001). Conclusion: Short-term oral folic acid (5 mg/day) supplementation with or without methylcobalamin appeared to be an effective approach to decrease Hcy levels and increase HTase/PON activity in patients with type 2 diabetes. A decrease in plasma Hcy levels may partly account for the elevation of serum HTase/PON activity. This could be a novel mechanism to protect against vascular diabetic complications.