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(Circulation. 2002;106:2760.)
© 2002 American Heart Association, Inc.

Editorial

Diabetic Macrovascular Disease

The Glucose Paradox?

Peter Libby, MD; Jorge Plutzky, MD

From The Leducq Center for Cardiovascular Research, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Peter Libby, MD, The Leducq Center for Cardiovascular Research, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, EBRC 307, Boston, MA 02115. E-mail plibby@rics.bwh.harvard.edu

Key Words: Editorials • atherosclerosis • diabetes mellitus • lipid • risk factors

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The cardiology community is awakening to a rampant epidemic of type II diabetes and its common companion, the metabolic syndrome. As the ponderosity of the US population increases, the morbid constellation of obesity, hypertension, glucose intolerance, insulin resistance, and dyslipidemia (characterized by abundant triglyceride (TG)–rich lipoproteins, low levels of atheroprotective high-density lipoprotein [HDL], and small, dense low-density lipoprotein [LDL] particles) is on the rise.¹ Pioneering work from several laboratories has provided us with pathophysiological insight for understanding some of diabetes’ vascular complications. In the face of hyperglycemia, glucose molecules conjugate by a nonenzymatic mechanism with the reactive side chains of the amino acid lysine on protein molecules (Figure). Through a series of well-understood chemical reactions, this nonenzymatic glycation can ultimately generate higher molecular weight condensates known as advanced glycation end products (AGE).^2,3 The formation of caramel from sugar provides a simple analogy for this process. Such reactions can be quite pervasive—occurring both inside and outside the cell, chemically modifying and potentially altering the functions not just of proteins, but of lipids and nucleic acids as well.

View larger version (42K): [in this window] [in a new window]   Multiple mechanisms contribute to arterial disease in patients with type II diabetes. A variety of risk factors converge on the artery to promote atherogenesis in individuals with type II diabetes (center). Skeletal muscles may be resistant of insulin action, which decreases the utilization of glucose and free fatty acids, causing hyperglycemia and increased levels of circulating free fatty acids. In the face of the insulin resistance, the pancreas initially attempts to compensate . . . [Full Text of this Article]

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