Mangoni Arduino A, Sherwood Roy A, Asonganyi Belinda, Swift Cameron G, Thomas Stephen, Jackson Stephen H D
Department of Clinical Pharmacology, Centre for Neuroscience, Flinders University, School of Medicine, Adelaide, Australia.
Am J Hypertens. 2005 Feb;18(2 Pt 1):220-6. doi: 10.1016/j.amjhyper.2004.08.036.
Endothelial dysfunction and arterial stiffening are commonly observed in type 2 diabetes. These abnormalities might be secondary to increased plasma concentrations of homocysteine. We sought to determine whether oral folic acid supplementation, by lowering homocysteine levels, enhanced endothelial function and reduced arterial stiffness in type 2 diabetes.
Twenty-six type 2 diabetic patients (age 56.5 +/- 0.9 years, diabetes duration 5.5 +/- 0.6 years, means +/- SEM) with no history of cardiovascular disease received 5 mg/d of oral folic acid or placebo for 4 weeks in a double-blind, randomized controlled, parallel group trial. The following parameters were measured before and after treatment: 1) endothelial function (forearm arterial blood flow during local intra-arterial administration of endothelium-dependent [acetylcholine 1.5, 4.5, and 15 microg/min] and endothelium-independent [sodium nitroprusside 1, 2, and 4 microg/min] vasodilators); and 2) carotid-radial and carotid-femoral pulse wave velocity.
Folic acid reduced plasma homocysteine concentrations and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (mean and 95% confidence interval post versus pretreatment differences in forearm arterial blood flow ratio between the infused and control arm +0.19 (0.03-0.35), P < .01; +0.39 (0.02-0.81), P < .05; and +0.40 (0.09-0.89), P < .05, respectively). Endothelium-independent vasodilatation and pulse wave velocity were not affected. No significant changes in forearm arterial blood flow and pulse wave velocity were observed in the placebo group. Multiple regression analysis showed that changes in folic acid, but not homocysteine, concentrations independently described changes in maximal endothelium-dependent vasodilatation.
Short-term oral folic acid supplementation significantly enhances endothelial function in type 2 diabetic patients, independent of homocysteine lowering.
2型糖尿病患者常出现内皮功能障碍和动脉僵硬。这些异常可能继发于血浆同型半胱氨酸浓度升高。我们试图确定口服叶酸补充剂是否通过降低同型半胱氨酸水平来增强2型糖尿病患者的内皮功能并降低动脉僵硬程度。
26例无心血管疾病史的2型糖尿病患者(年龄56.5±0.9岁,糖尿病病程5.5±0.6年,均值±标准误)在一项双盲、随机对照、平行组试验中接受5mg/d的口服叶酸或安慰剂治疗4周。在治疗前后测量以下参数:1)内皮功能(局部动脉内给予内皮依赖性[乙酰胆碱1.5、4.5和15μg/min]和内皮非依赖性[硝普钠1、2和4μg/min]血管扩张剂期间的前臂动脉血流量);2)颈-桡和颈-股脉搏波速度。
叶酸降低了血浆同型半胱氨酸浓度,并在每次乙酰胆碱输注速率下增强了内皮依赖性血管扩张(输注臂与对照臂之间前臂动脉血流量比值的均值和95%置信区间,治疗后与治疗前的差异分别为+0.19(0.03 - 0.35),P <.01;+0.39(0.02 - 0.81),P <.05;和+0.40(0.09 - 0.89),P <.05)。内皮非依赖性血管扩张和脉搏波速度未受影响。安慰剂组前臂动脉血流量和脉搏波速度无显著变化。多元回归分析表明,叶酸浓度的变化而非同型半胱氨酸浓度的变化独立描述了最大内皮依赖性血管扩张的变化。
短期口服叶酸补充剂可显著增强2型糖尿病患者的内皮功能,与降低同型半胱氨酸水平无关。