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Insulin resistance functionally limits endothelium-dependent coronary vasodilation in nondiabetic patients

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Abstract

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 μg/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/m2 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/m2 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 μg/ml per minute) and moderate (3 μg/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 μg] = 85.9 + 0.35 [M values], r = 0.58, P = 0.038; [%VFI Ach 1 μg] = 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.

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Authors and Affiliations

  1. Second Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-0061, Japan

    Noriyuki Fujii, Kazufumi Tsuchihashi, Hisataka Sasao, Mariko Eguchi, Hideyuki Miurakami, Mamoru Hase, Katsuhiro Higashiura, Satoshi Yuda, Akiyoshi Hashimoto, Tetsuji Miura, Nobuyuki Ura & Kazuaki Shimamoto

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  1. Noriyuki Fujii
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  2. Kazufumi Tsuchihashi
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Correspondence to Kazufumi Tsuchihashi.

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Fujii, N., Tsuchihashi, K., Sasao, H. et al. Insulin resistance functionally limits endothelium-dependent coronary vasodilation in nondiabetic patients. Heart Vessels 23, 9–15 (2008). https://doi.org/10.1007/s00380-007-1002-0

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  • DOI: https://doi.org/10.1007/s00380-007-1002-0

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