Advanced glycation end-products in microvascular complications of type 2 diabetes: Are they “major actors” in metabolic memory?

An excess of advanced glycation end-products (AGE) is one of the most important mechanisms in the pathophysiology of chronic diabetic complications. This review summarizes the role of these compounds in microvascular pathogenesis, particularly in the light of recently proposed biochemical mechanisms for diabetic retinopathy, nephropathy and neuropathy. Then we focus on the relationship between AGE and “metabolic memory”, to clarify AGE’s role in the link between micro- and macrovascular complications. Recent studies indicate AGE not so much as “actors”, and more as “directors” of processes leading to these complications. They have several intra- and extracellular targets, so they can be seen as a “bridge” between intra- and extracellular damage. This may partly explain the clinical link between micro- and macrovascular disease in diabetes, and help clarify the mechanisms behind metabolic memory. The pathophysiological cascades triggered by AGE have a dominant, hyperglycemia-independent role in the microvascular complications of diabetes so prevention and treatment must focus not only on early glycemic control, but also on reducing the factors related to glycooxidative stress.