Fujii Noriyuki, Tsuchihashi Kazufumi, Sasao Hisataka, Eguchi Mariko, Miurakami Hideyuki, Hase Mamoru, Higashiura Katsuhiro, Yuda Satoshi, Hashimoto Akiyoshi, Miura Tetsuji, Ura Nobuyuki, Shimamoto Kazuaki
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-0061, Japan.
Heart Vessels. 2008 Jan;23(1):9-15. doi: 10.1007/s00380-007-1002-0. Epub 2008 Feb 14.
Insulin resistance (IR) is now considered to be a risk factor for coronary arterial atherosclerosis and is likely to be involved in a limited endothelium-dependent vasodilatory function in peripheral circulation. We investigated whether IR impairs endothelial vasodilator function in the noninfarcted coronary artery. In 14 nondiabetic patients (10 males, 66 +/- 6 years) who were selected from 214 patients underwent IR evaluation by glucose clamp, a Doppler flow wire was used to measure coronary flow changes (percent volume flow index, %VFI) during intracoronary administration of papaverin (10 mg) and stepwise administration of acetylcholine (Ach; 1, 3, 10 microg/ml per minute) into the non-infarcted left circumflex coronary artery. Insulin resistance was comparatively evaluated by an euglycemic hyperinsulinemic glucose clamp (M value, mg/m(2) per minute) or by a 75g-oral glucose tolerance test (120-min immunoreactive insulin; 120' IRI, pmol/l). Eight patients (57%) were defined as having IR on the basis of results obtained by both the glucose clamp method (M values <167 mg/m(2) per minute) and 120' IRI (>384 pmol/l). There was no difference between papaverin-induced %VFI increases in IR and non-IR subjects (328% +/- 43% vs. 361% +/- 87%). However, IR subjects showed significantly lower Ach-induced %VFI increases in a dose-dependent manner (P < 0.05), especially when low (1 microg/ml per minute) and moderate (3 microg/ml per minute) doses of Ach were used (165% +/- 18% or 248% +/- 29% in non-IR subjects vs. 130% +/- 20% or 183% +/- 41% in IR subjects, P < 0.001, respectively). Moreover, %VFI increase at a low dose of Ach infusion significantly correlated with M values or 120' IRI ([%VFI Ach 1 microg] = 85.9 + 0.35 [M values], r = 0.58, P = 0.038; [%VFI Ach 1 microg] = 176.8 - 0.47.[120' IRI], r = -0.57, P = 0.035). Insulin resistance limits endothelium-dependent coronary vasodilation in association with the severity of IR in non-diabetic patients.
胰岛素抵抗（IR）现被认为是冠状动脉粥样硬化的一个危险因素，并且可能与外周循环中有限的内皮依赖性血管舒张功能有关。我们研究了IR是否会损害非梗死冠状动脉的内皮舒张功能。在从214例接受葡萄糖钳夹法进行IR评估的患者中选出的14例非糖尿病患者（10例男性，66±6岁）中，使用多普勒血流导丝测量在非梗死左旋冠状动脉内注射罂粟碱（10mg）以及逐步注射乙酰胆碱（Ach；每分钟1、3、10μg/ml）期间的冠状动脉血流变化（每搏量容积流量指数，%VFI）。通过正常血糖高胰岛素葡萄糖钳夹法（M值，mg/m²每分钟）或75g口服葡萄糖耐量试验（120分钟免疫反应性胰岛素；120' IRI，pmol/l）对胰岛素抵抗进行比较评估。根据葡萄糖钳夹法（M值<167mg/m²每分钟）和120' IRI（>384pmol/l）获得的结果，8例患者（57%）被定义为存在IR。IR组和非IR组中罂粟碱诱导的%VFI增加无差异（328%±43%对361%±87%）。然而，IR组患者中Ach诱导的%VFI增加呈剂量依赖性显著降低（P<0.05），尤其是在使用低剂量（每分钟1μg/ml）和中等剂量（每分钟3μg/ml）Ach时（非IR组中为165%±18%或248%±29%，IR组中为130%±20%或183%±41%，P分别<0.001）。此外，低剂量Ach输注时的%VFI增加与M值或120' IRI显著相关（[Ach 1μg时的%VFI]=85.9 + 0.35[M值]，r = 0.58，P = 0.038；[Ach 1μg时的%VFI]=176.8 - 0.47·[120' IRI]，r = -0.57，P = 0.035）。在非糖尿病患者中，胰岛素抵抗会限制内皮依赖性冠状动脉舒张，且与IR的严重程度相关。
