Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting

Abstract

Background-Previously undiagnosed diabetes, impaired glucose tolerance, and insulin resistance are common in patients with acute myocardial infarction and coronary heart disease (CHD) and might be involved in early restenosis after stent implantation. To evaluate whether markers of insulin resistance syndrome, including leptin, and endothelial dysfunction are related to increased rate of early restenosis, we studied nondiabetic patients with CHD after successful coronary stenting. Methods and Results-Both patients with CHD undergoing coronary stenting (120 patients) and control subjects (58 patients) were submitted to an oral glucose tolerance test (OGTT). Fasting leptin levels and fasting and postglucose load insulin sensitivity were assessed. Endothelial function was measured by nitrite and nitrate release (NOx) during OGTT. More than 50% of patients treated with stent implantation presented impaired glucose tolerance or type 2 diabetes, which was previously undiagnosed. These patients also had higher glucose, insulin, and leptin levels than control subjects. Among the stented patients, insulin and leptin levels were higher in patients with restenosis than in patients without restenosis. A significant increase in NOx levels was found during OGTT both in patients without restenosis and in control subjects. On the contrary, NOx profiles were blunted in patients with restenosis. At multiple regression analysis, only ⌬AUC-NOx areas and insulin sensitivity index showed an independent correlation with the minimal lumen diameter at follow-up. Conclusions-We demonstrated that insulin resistance and endothelial dysfunction are independent predictors of early restenosis after coronary stenting.

Role of Endothelial Dysfunction and Insulin Resistance in Angina Pectoris and Normal Coronary Angiogram

“…On the other hand, patients with metabolic syndrome X show a cluster of symptoms characterized by insulin resistance, hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia, visceral obesity, hypertension, and high risk for cardiovascular disease [1,41,46,51]. Recently, our group studied the insulin action on muscle glucose metabolism and endothelial function in the two groups of patients [47].…”

New directions in the treatment of heart failure: Targeting free fatty acid oxidation

“…On the other hand, insulin resistance is a pathologic condition that is rarely diagnosed as a distinct entity. In a recent study, our group has shown that more than 50% of patients receiving coronary stenting for ischemic heart disease and having normal baseline blood glucose levels present abnormal hyperglycemia after an oral glucose tolerance test [41]. These abnormalities are associated with a higher probability of restenosis [41].…”

“…In a recent study, our group has shown that more than 50% of patients receiving coronary stenting for ischemic heart disease and having normal baseline blood glucose levels present abnormal hyperglycemia after an oral glucose tolerance test [41]. These abnormalities are associated with a higher probability of restenosis [41]. These results are supported by previous studies showing that patients with impaired glucose tolerance not only run the risk of developing overt diabetes and its associated microvascular complications but also have an increased risk of cardiovascular morbidity and mortality compared with healthy, glucose-tolerant patients [42].…”

Update on the Role of Adipokines in Atherosclerosis and Cardiovascular Diseases

“…Elevated leptin levels are associated with increased risk of developing coronary heart diseases [24], including acute myocardial infarction [25] and restenosis after angioplasty [26], as well as left cardiac hypertrophy [27] and chronic heart failure [28]. Leptin levels are also associated with risk of stroke, both hemorrhagic and ischemic [29].…”