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Abstract
Although the underlying causes of hyperglycemia are multiple, a common thread associated
with high levels of blood sugar is the development of a range of vascular and inflammatory
complications that might seriously limit the quality and duration of life in affected
individuals. Despite multiple aggressive efforts to prevent complications, diabetes
remains the leading disease consuming healthcare dollars in the USA. This review focuses
on the role of advanced glycation endproducts (AGEs) and their interaction with their
signal-transduction AGE receptor (RAGE), in vascular and inflammatory cell perturbation
and the chronic activation that underlies diabetes. Our studies provide mechanistic
insights into complications within the macrovasculature and those ensuing from an
exaggerated host response to invading bacteria, and suggest that blockade of RAGE
might provide a potent and safe strategy for the prevention of complications that
typify long-term diabetes.