Effect of Insulin Resistance on the Endothelial Vasomotor Function of the Coronary Artery of Nondiabetic Patients

Abstract

nsulin resistance is a state in which cells and organs have decreased sensitivity to insulin and individuals with insulin resistance have reduced glucose uptake. 'Syndrome X', proposed by Reaven in 1988, 1 is characterized by insulin resistance, abnormal glucose tolerance, hyperinsulinemia, increased VLDL-triglyceride, decreased HDL-cholesterol, and hypertension. He reported that patients with this syndrome have a high risk for ischemic heart disease. Kaplan added the concept of obesity to Syndrome X. 2 The 'deadly quartet' is characterized by upper-body obesity, glucose intolerance, hypertriglycemia, and hypertension. Thus, insulin resistance is associated not only with metabolic diseases, but also with arteriosclerotic diseases such as ischemic heart disease. We studied the relationship between insulin resistance and the endothelial vasomotor function of the coronary artery of nondiabetic patients, and discuss the significance of insulin resistance in coronary artery disease (CAD). Methods Study SubjectsTwenty-five subjects with chest symptoms and a positive exercise tolerance test, who did not have diabetes mellitus by the hemoglobin A1C test and the fasting value of blood glucose (FBS), were included in this study. None Japanese Circulation Journal Vol.63, August 1999 of the subjects had significant stenosis of the right coronary artery (RCA); the stenosis in each case was less than 25% by American Heart Association (AHA) classification. Written informed consent was obtained from all 25 patients and their family members after explaining the protocol of the present study. The patients ranged in age between 39 and 68 years (mean ± SD: 57.2±9.1), and included 15 females and 10 males. Coronary Flow VelocityAbsence of significant stenosis of the RCA was confirmed by the Judkins technique. A 0.018F flow wire (Cardiometrics, Mountain View, CA, USA) was inserted into the RCA to measure the coronary flow velocity, which was measured after it became steady. Following initial measurement of the baseline velocity, physiological saline was injected into the RCA at an infusion rate of 1 ml/min through a 5F Judkins catheter for 2 min. The following drugs were then each injected at least 5 min after administration of the previous drug and after the initial flow velocity was restored. First, acetylcholine (Ach; Daiichi Seiyaku, Tokyo, Japan) at a concentration of 2 g ml -1 min -1 was injected for 2 min. The average peak flow velocity (APV) and coronary angiogram were recorded. When the flow velocity returned to its initial level, 20 g ml -1 min -1 of Ach was injected for 2 min after which the APV and coronary angiogram were recorded. Next, 10 mg of papaverine hydrochloride (PAP; Nihon Seiyaku, Tokyo, Japan) was injected over 5 s, soon after which the APV and coronary angiogram were recorded. Finally, a bolus dose (2 mg) of isosorbide dinitrate (ISDN; Eisai, Tokyo, Japan) was injected, and again the APV and coronary angiogram were recorded. The coronary artery flow velocity, blood pressure, heart rate, and 12-lead electroc...

The Relation Between Insulin Resistance Determined by Haemostatic Modelling and Slow Coronary Flow

“…[20][21][22] Insulin resistance is related to the vasomotor dysfunction of the endothelial cells that line the coronary artery. 23,24 It is well known that endothelial function is impaired in patients with SCF. 2,25 In our study, we evaluated the effect of impaired glucose metabolism and insulin resistance that may play some role in the physiopathology of SCF.…”

Hyperinsulinemia as a Risk Factor for Restenosis After Coronary Balloon Angioplasty.

“…4 Vasospasm of the dilated coronary segment is frequently accompanied by restenosis, 25 and loss of the endothelium-derived relaxing factor, nitric oxide caused by endothelial denudation, promotes vasospasm, platelet aggregation, and SMC proliferation. 31,32 Hypersecretion of insulin may therefore contribute to the pathogenesis of severe coronary vasospasm and increase susceptibility to restenosis, [33][34][35] although the relation of vasospastic angina to restenosis is still unclear.…”