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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1693.)
© 2006 American Heart Association, Inc.

Brief Reviews

Diabetic Vascular Disease

An Experimental Objective

Ira J. Goldberg; Hayes M. Dansky

From Divisions of Preventive Medicine and Nutrition (I.J.G.) and Cardiology (I.J.G., H.M.D.), Department of Medicine, Columbia University, New York, NY.

Correspondence to Ira J. Goldberg, Medicine, 630 West 168th Street, New York, NY 10032. E-mail ijg3{at}columbia.edu

Series Editor: Richard A. Cohen
Diabetic Vascular Disease: Pathophysiological Mechanisms in the Diabetic Milieu and Therapeutic Implications
ATVB In Focus

Previous Brief Reviews in this Series:

•Naka Y, Bucciarelli LG, Wendt T, Lee LK, Rong LL, Ramasamy R, Yan SF, Schmidt AM. RAGE axis: animal models and novel insights into the vascular complications of diabetes. 2004;24:1342–1349.
•Natarajan R, Nadler JL. Lipid inflammatory mediators in diabetic vascular disease. 2004;24:1542–1548.
•Rask-Madsen C, King GL. Proatherosclerotic mechanisms involving protein kinase C in diabetes and insulin resistance. 2005;25:487–496.
•Blaschke F, Takata Y, Caglayan E, Law RE, Hsueh WA. Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. 2006;26:28–40.

It is well known that humans with diabetes have more atherosclerosis and its complications. The causes of this relationship are, however, unclear. Although recent data show that improved glycemic control reduces arterial disease in type 1 diabetes, other studies have shown that subjects with "prediabetes" have more cardiovascular disease before the development of hyperglycemia. Thus, either hyperglycemia and/or lack of insulin actions are toxic to arteries, or metabolic derangements exclusive of hyperglycemia are atherogenic. For >50 years animal models of diabetes and atherosclerosis have been used to uncover potential mechanisms underlying diabetes associated cardiovascular disease. Surprisingly, diabetes alone increases vascular disease in only a few select animal models. Increased atherosclerosis has been found in several animals and lines of genetically modified mice; however, diabetes often also leads to greater hyperlipidemia. This makes it difficult to separate the toxic effects of insulin lack and/or hyperglycemia from those caused by the lipids. These studies are reviewed, as well as more recent investigations using new methods to create diabetic-atherosclerotic models.

Despite a plethora of in vitro data showing toxic effects of hyperglycemia, accelerated atherosclerosis does not always accompany diabetes in animals. This might result from genetic differences, time course, or because risk factors, such as hyperlipidemia, are present and overwhelm any toxic effects of hyperglycemia.

Key Words: macrovascular • lipoproteins • atherosclerosis • hyperglycemia • endothelial cells • macrophages

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