Current concepts in insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome

• Published in: The American journal of cardiology Vol. 90; no. 5; pp. 19 - 26
• Main Author: Reusch, Jane E.B
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 05.09.2002; Elsevier; Elsevier Limited
• Subjects: Associated diseases and complications; Biological and medical sciences; Cardiovascular disease; Coronary Disease - physiopathology; Coronary Disease - radiotherapy; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Humans; Hyperlipidemias - etiology; Hyperlipidemias - physiopathology; Hypoglycemic Agents - pharmacology; Insulin; Insulin - physiology; Insulin Resistance - physiology; Medical sciences; Metabolic Syndrome - complications; Metabolic Syndrome - drug therapy; Metabolic Syndrome - physiopathology; Physical Fitness; Risk Factors; Thiazoles - pharmacology; Thrombosis - etiology; Thrombosis - physiopathology; Vasodilation - drug effects; Endocrinopathy; Human; Pathophysiology; Treatment efficiency; Cardiovascular disease; Metabolic diseases; Thiazolidinedione derivatives; Non insulin dependent diabetes; Fibrinolysis; Insulin; Prevention; Target tissue resistance; Hypoglycemic agent; Concomitant disease; Chemotherapy; Treatment; Risk factor; Complication
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(02)02555-9

A clustering of risk factors, including elevated triglycerides, decreased high-density lipoprotein cholesterol, hyperinsulinemia, and hypertension often are observed in patients who are insulin resistant. Insulin resistance has been found to play a critical role in the development of cardiovascular disease, particularly in patients with type 2 diabetes. Patients with insulin resistance have an increase in small, dense low-density lipoprotein (LDL) cholesterol, which is more atherogenic than large, buoyant LDL cholesterol. In the context of insulin resistance, insulin has reduced effects on the phosphatidylinositol 3 kinase (PI3K) pathway, whereas mitogen-activated protein kinase activity is maintained. The result is an exaggeration of the mitogenic actions of insulin leading to vascular smooth muscle proliferation and elevated plasminogen activator inhibitor (PAI)-1. Notably, nitric oxide–mediated vasodilation also is impaired, further contributing to atherogenicity. In addition, hyperinsulinemia further contributes to cardiovascular risk by promoting thrombosis. Patients who are insulin resistant have decreased fibrinolysis, as indicated by increased levels of PAI-1. Studies have shown that enhancing insulin sensitivity with insulin sensitizers, such as thiazolidinediones, may improve insulin resistance and limit the development of adverse cardiovascular consequences.