title: Insulin resistance functionally limits endothelium-dependent coronary vasodilation in nondiabetic patients.
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 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.
authors.affiliation: Second Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-0061, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fujii
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Tsuchihashi
authors.forename: Hisataka
authors.initials: H
authors.lastname: Sasao
authors.forename: Mariko
authors.initials: M
authors.lastname: Eguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Miurakami
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hase
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Higashiura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuda
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ura
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism*; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000502:physiology; D023921:Coronary Stenosis / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003920:Diabetes Mellitus; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D018608:Ultrasonography, Doppler; D014664:Vasodilation / Q000502:physiology*
chemical_list: D001786:Blood Glucose