Effect of Insulin Resistance on Coronary Endothelial Dysfunction

摘要

It is widely accepted that metabolic syndrome is related to cardiovascular disease and that insulin resistance is one of causes of metabolic syndrome. It has been reported that hyperinsulinemia is an independent risk factor for ischemic heart disease. Insulin resistance with hyperinsulinemia is associated with hypertension, glucose intolerance, obesity, and dyslipoproteinemia of low high-density lipoprotein-cholesterol (HDL-C) levels or hypertriglyceridemia, which are well-known risk factors for coronary artery disease. Acute myocardial infarction (AMI) patients with hyperglycaemia on admission, independent of a history of diabetes, represent a high-risk population for mortality. There are significantly different two groups in non diabetic patients with AMI from the point of view of insulin resistance. One is an insulin resistance group, and the other is a no insulin resistance group. Homeostasis model assessment insulin resistance (HOMA-IR) was the highest value on admission and decreased to a steady state until 2 weeks in the insulin resistance group, and was no change in the no insulin resistance group. HOMA-IR of the insulin resistance group was higher than that of the no insulin resistance group until four months after percutaneous coronary intervention (PCI). The insulin resistance in no diabetic patients with AMI consists of the transient insulin resistance and the continuous insulin resistance. This transient insulin resistance (HOMA-IR over 2.0) is dependent on hyperglycaemia and hyperinsulinemia, and correlated with thyroid stimulating hormone, glucagon, and cortisol. The continuous insulin resistance (HOMA-IR under 2.0 and over 1.0) correlated with leptin and contributed to restenosis after coronary stenting. Insulin resistance is an independent risk factor for restenosis after coronary bare-metal stenting. Relative risk (RR) of insulin resistance to restenosis is stronger than those of treated diabetes mellitus and treated hyperlipidemia. [insulin resistance: RR 2.06; 95% confidence interval (CI), 1.20-3.56, diabetes mellitus: RR 1.92; 95% CI, 1.25-2.95, hyperlipidemia: RR 0.69; 95% CI, 0.44-1.10]. HOMA-IR and glycosylated hemoglobin (HbAlc) were associated with restenosis after coronary stenting, and HbAlc and low-density lipoprotein cholesterol were associated with de-novo stenosis. These results may be reflected in histological differences between neointimal tissue proliferation as restenosis and atherosclerosis as de-novo stenosis. Recent studies suggested that thiazolidinediones, which are novel insulin-sensitizing agents, effectively reduced restenosis and the risk of repeat target vessel revascularization. The treatment with pioglitazone in type 2 diabetic patients significantly reduced leptin. This decreased leptin improved insulin resistance and endothelial function with the reduction of insulin. The improved endothelial function affected the reduction of in-stent restenosis.