Ceriello Antonio, Piconi Ludovica, Esposito Katherine, Giugliano Dario
Centre of Excellence in Diabetes and Endocrinology, University Hospital of Coventry and Warwickshire, Warwick Medical School, University of Warwick, Coventry, UK.
Diabetes Care. 2007 Jul;30(7):1694-8. doi: 10.2337/dc07-0318. Epub 2007 Apr 24.
Long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations of endothelial function by increased oxidative stress, even when glycemia is normalized.
In this study, 36 type 1 diabetic patients and 12 control subjects were enrolled. The diabetic patients were divided into three groups. The first group was treated for 24 h with insulin, achieving a near normalization of glycemia. After 12 h of this treatment, vitamin C was added for the remaining 12 h. The second group was treated for 24 h with vitamin C. After 12 h of this treatment, insulin was started, achieving a near normalization of glycemia for the remaining 12 h. The third group was treated for 24 h with both vitamin C and insulin, achieving near normalization of glycemia. The same protocols were performed after 1 month of telmisartan or placebo.
Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels. Telmisartan significantly improved basal endothelial function and decreased nitrotyrosine plasma levels. In patients treated with telmisartan, a near normalization of both flow-mediated vasodilation and oxidative stress was achieved when glycemia was normalized, whereas adding vitamin C infusion did not show further effect on endothelial function or nitrotyrosine plasma levels.
These data indicate that combining the normalization of glycemia with an antioxidant can normalize endothelial function in type 1 diabetic patients and that telmisartan works as an antioxidant like vitamin C.
1型糖尿病患者长期高血糖会通过增加氧化应激诱导内皮功能发生永久性改变,即使血糖恢复正常也是如此。
本研究纳入了36例1型糖尿病患者和12例对照受试者。糖尿病患者被分为三组。第一组用胰岛素治疗24小时,使血糖接近正常。在该治疗12小时后,添加维生素C再治疗12小时。第二组用维生素C治疗24小时。在该治疗12小时后,开始使用胰岛素,使血糖在剩余12小时接近正常。第三组同时用维生素C和胰岛素治疗24小时,使血糖接近正常。在服用替米沙坦或安慰剂1个月后执行相同方案。
血糖正常化或单独使用维生素C治疗均无法使内皮功能障碍或氧化应激恢复正常。胰岛素与维生素C联合使用可使内皮功能障碍恢复正常,并将氧化应激降低至正常水平。替米沙坦显著改善基础内皮功能并降低血浆硝基酪氨酸水平。在接受替米沙坦治疗的患者中,当血糖正常化时,血流介导的血管舒张和氧化应激均接近正常,而添加维生素C输注对内皮功能或血浆硝基酪氨酸水平未显示进一步影响。
这些数据表明,将血糖正常化与抗氧化剂联合使用可使1型糖尿病患者的内皮功能恢复正常,并且替米沙坦与维生素C一样具有抗氧化作用。