Schalkwijk C G, Smulders R A, Lambert J, Donker A J, Stehouwer C D
Department of Clinical Chemistry, Academisch Ziekenhuis Vrije Universiteit, and Institute for Cardiovascular Research (ICaR), Vrije Universiteit, Amsterdam, The Netherlands.
Eur J Clin Invest. 2000 Oct;30(10):853-60. doi: 10.1046/j.1365-2362.2000.00721.x.
The usefulness of treatment with an angiotensin-converting enzyme-inhibitor (ACE-inhibitor) in normotensive patients with type 1 diabetes is controversial. We investigated whether ACE-inhibition improves endothelial function in such patients and compared the responses to those in healthy subjects.
We studied 23 healthy volunteers (controls, aged 29.8 [SD 7.0] years) and 24 type 1 diabetic patients (aged 28.7 [9. 6] years; HbA1c 8.1 [1.2]%; diabetes duration 13.8 [2-30] years; blood pressure < 140/90 mm Hg; 7 with microalbuminuria) after 5 weeks of ACE-inhibition (quinapril, 10 mg day-1) and placebo in a randomized, double-blind cross-over design. Estimates of endothelial function obtained were by flow-mediated vasodilation and plasma levels of endothelium-derived proteins.
As estimated from the measurements on placebo, type 1 diabetic patients, as compared to the controls, had some impairment of endothelial function: plasma tissue-type plasminogen activator levels were lower (3.5 vs. 5.4 ng mL(-1), P<0.05), but there were no significant differences in brachial artery flow-mediated vasodilation or plasma levels of von Willebrand Factor, endothelin-1, plasminogen activator inhibitor-1, soluble E-selectin or vascular cell adhesion molecule-1. As compared to placebo, ACE-inhibition increased flow-mediated vasodilation in controls (by 3.84% points [95% CI, 0.66 - 7.02], P<0.05), but not in type 1 diabetic patients (0.82% points [95% CI, -2.72 - 4.36], P = 0.64; P = 0.08 vs. controls). On ACE-inhibition soluble E-selectin levels decreased both in controls (from 43.0 to 37.0 ng mL(-1), P<0.01) and in type 1 diabetic patients (from 41.0 to 39.0 ng mL(-1), P = 0.09). Other endothelial markers did not change during ACE-inhibition.
Normotensive type 1 diabetic patients with normoalbuminara or microalbuminuria have mild endothelial dysfunction. Short-term ACE-inhibition improves endothelial function as reflected by a decreased sE-selectin in healthy subjects and in normotensive type 1 diabetic patients. In healthy subjects, ACE-inhibition increases flow-mediated vasodilation. In contrast, in type 1 diabetic patients, ACE-inhibition does not affect flow-mediated vasodilation.
血管紧张素转换酶抑制剂（ACE抑制剂）用于1型糖尿病血压正常患者的疗效存在争议。我们研究了ACE抑制是否能改善此类患者的内皮功能，并将其反应与健康受试者进行比较。
我们采用随机、双盲交叉设计，对23名健康志愿者（对照组，年龄29.8[标准差7.0]岁）和24名1型糖尿病患者（年龄28.7[9.6]岁；糖化血红蛋白8.1[1.2]%；糖尿病病程13.8[2 - 30]年；血压<140/90 mmHg；7例有微量白蛋白尿）进行了为期5周的ACE抑制（喹那普利，10 mg/天）和安慰剂治疗。通过血流介导的血管舒张和内皮衍生蛋白的血浆水平来评估内皮功能。
根据安慰剂测量结果估计，与对照组相比，1型糖尿病患者存在一定程度的内皮功能损害：血浆组织型纤溶酶原激活剂水平较低（3.5 vs. 5.4 ng/mL，P<0.05），但肱动脉血流介导的血管舒张或血管性血友病因子、内皮素-1、纤溶酶原激活剂抑制剂-1、可溶性E选择素或血管细胞黏附分子-1的血浆水平无显著差异。与安慰剂相比，ACE抑制使对照组的血流介导的血管舒张增加（增加3.84个百分点[95%可信区间，0.66 - 7.02]，P<0.05），但在1型糖尿病患者中未增加（0.82个百分点[95%可信区间，-2.72 - 4.36]，P = 0.64；与对照组相比P = 0.08）。ACE抑制后，对照组和1型糖尿病患者的可溶性E选择素水平均降低（对照组从43.0降至37.0 ng/mL，P<0.01；1型糖尿病患者从41.0降至39.0 ng/mL，P = 0.09）。ACE抑制期间其他内皮标志物未发生变化。
正常白蛋白尿或微量白蛋白尿的血压正常的1型糖尿病患者存在轻度内皮功能障碍。短期ACE抑制可改善内皮功能，这在健康受试者和血压正常的1型糖尿病患者中表现为可溶性E选择素降低。在健康受试者中，ACE抑制可增加血流介导的血管舒张。相比之下，在1型糖尿病患者中，ACE抑制不影响血流介导的血管舒张。
