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.

Hyperleptinemia as a Robust Risk Factor of Coronary Artery Disease and Metabolic Syndrome in Type 2 Diabetic Patients

“…However, there are emerging evidences to suggest that leptin may mediate the adverse effects on the cardiovascular system. Higher leptin concentrations are associated with an impaired arterial distensibility [20], and patients with a restenosis after coronary stenting had higher leptin levels than those without a restenosis [21]. Furthermore, the direct influence of leptin on the vascular biology is supported by the ob/ob mice, which lacks leptin and consequently becomes hyperphagia and obesity but is nevertheless resistant to atherosclerosis [22].…”

A Randomized Comparison of Pioglitazone to Inhibit Restenosis After Coronary Stenting in Patients With Type 2 Diabetes

“…Recent studies showed that insulin resistance is an independent predictor of early restenosis after coronary stenting (7) and is associated with an increased incidence of myocardial infarction and death (8). Takagi and colleagues (9,10) demonstrated that troglitazone reduces neointimal tissue proliferation after coronary stent implantation, but pioglitazone does not reduce in-stent restenosis significantly.…”

Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin resistance and the metabolic syndrome

“…Interestingly, patients with insulin resistance and hyperglycemia in association with obesity in the form of the metabolic syndrome have also been shown to have a similar propensity toward aggressive cardiovascular disease (17,37). Undiagnosed and unrecognized "diabetic" patients with insulin resistance and elevated oral glucose tolerance tests have also been shown to have worse outcomes following vascular interventions (44).…”