The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

Abstract

Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

Figure 1

Simplified scheme of the complex Maillard reaction and formation of some advanced glycation endproducts (AGEs) in vivo. CEL = carboxyethyllysine; MOLD = methylglyoxal lysine dimer; DOLD, 3-deoxyglucosone lysine dimer; CML, carboxymethyllysine; GOLD, glyoxal lysine dimer.

Figure 2

Pathogenetic effects of advanced glycation endproducts (AGEs). By binding and crosslinking extracellular matrix, e.g. collagen, AGEs induces vascular stiffness en increases vascular permeability. The interaction with AGE receptors (e.g. RAGE) induces endothelial dysfunction by reducing nitric oxide (NO), inflammatory reactions, and oxidative stress. Binding to lipoproteins increases the uptake of e.g. low density lipoproteins (LDL) by macrophages, which may lead to the formation of foam cells.