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- May 12, 2008 |
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"Endothelial Dysfunction in Diabetes"Dr. Todd Anderson (biography)
English - 2002-10-28 - 21 minutes
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Summary :
The healthy endothelium maintains vascular integrity though the release of a variety of paracrine factors such as nitric oxide. Nitric oxide is produced by endothelial cells from the essential amino acid I-arginine. Nitric oxide is anit-atherogenic by virtue of its ability to relax smooth muscle cells, inhibit platelet aggregation and smooth muscle cell proliferation and prevent leukocyte adhesion. In response to atherosclerotic risk factors, the endothelium becomes dysfunctional. This is likely the initiating event in atherosclerosis and is an important contributor to ischemic manifestations of coronary artery disease. Atherosclerotic vascular disease is the leading cause of death in patients with diabetes.
Endothelium-dependant vasodilator responses can be assessed in human coronary arteries and in the peripheral circulation. Patients with both Type-1 and Type-2 diabetes mellitus have been reported to have impairment of endothelium-dependent vasodilation. This abnormality also occurs in subjects with insulin resistance before overt diabetes is present. Putative mechanisms of endothelial dysfuntion in diabetes will be reviewd and put into clinical context. The most important mechanisms seem to involve abnormal endothelial function and hence lessen ischemic responses. These include cholesterol-lowering therapy, antioxidant therapy, ACE-inhibition, and hormonal replacement therapy in post-menopausal women. Recent studies have also looked at the impact of modulation of insulin resistance on endothelial function. The data for diabetes will be specifically reviewed.
Learning objectives :
The reader will: Learn to understand that atherosclerosis is the leading cause of death in patients with diabetes.
Learn to understand the pathogenesis of atherosclerosis in general and in diabetes specifically.
Learn the paracrine factors that regulate endothelial function.
Learn that oxidative stress plays a major role in endothelial dysfuntion, particularly diabetes.
Learn the interventions that have been shown to ameliorate endothelial dysfunction- such as lipid lowering, ACE-inhibition, anti-oxidant strategies, and more recently nitric oxide co-factors such as tetrahydrobiopterin and modulation of insulin resistance
Bibliographic references :
1. Diabetes Prevention Program Research Group. Reduction in the incidence of Type 2 diabetes with lifestyle intervention or metformin. New Engl J Med 2002; 346(6):393-403
2. Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation 2002; 105(5): 546-549
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