Abstract
A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs' involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer's disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.
Highlights
Diabetes is a global health challenge.In the recent report in the IDF Diabetes Atlas, the prevalence and number of diabetes cases in the world are estimated to be 8.3% and 387 million, and one person dies from diabetes every 7 s [1]
Glyceraldehyde, which could be derived from glucose metabolism, is not a major sugar in vivo and its incubation with proteins will generate a large number of advanced glycation end products (AGEs); in addition, there is some criticism that measurement of AGEs using liquid chromatography–tandem mass spectrometry technique may produce different results to that using enzyme-linked immunosorbent assay (ELISA) [129]
Our series of studies have suggested that serum levels of glyceraldehyde-derived AGEs might be a novel biomarker for insulin resistance and vascular injury and may predict future cardiovascular events in diabetes
Summary
Despite an early loss of glycemic differences between the original intensive therapy group and the conventional one, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up [18] These findings demonstrate that socalled “metabolic memory” may cause chronic abnormalities in diabetic vessels that are not reversed, even by subsequent, relatively good blood glucose control, suggesting a long-term beneficial influence of early metabolic control (that is, the legacy effect) on the risk of diabetic vascular complications and death in both type 1 and type 2 diabetic patients. The biochemical nature and mode of action of AGEs are most compatible with the concept of metabolic memory [28,29]
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