In this chapter, we discuss the role of advanced glycation end products
(AGE) in the pathogenesis of diabetes and its complications, as well as potential AGEfocused
treatment strategies. AGE are compounds that form as a result of chemical
reactions from the glycation of proteins and lipids. Glycation of proteins alters their
structure and function (extracellular effects), and AGE also bind to receptors which
promote inflammatory pathways (intracellular effects). AGE are formed endogenously
through normal metabolism and aging, and AGE formation is accelerated in certain
pathologic states such as diabetes (due to hyperglycemia) and oxidative stress (via
reactive oxygen species). AGE accumulation and deposition are reported in chronic
inflammatory diseases such as atherosclerosis and diabetes. AGE deposits form crosslinks
with matrix proteins resulting in increased stiffness of collagen, decreased
elasticity of vasculature, increased muscle stiffness and reduction in function. AGE can
also be formed through prolonged heating of food (such as frying and grilling). Tobacco
smoke is another source of exogenous AGE. High AGE diet is associated with
increasing weight gain, adiposity, and insulin resistance. Treatment approaches include
inhibiting AGE formation, breaking formed cross-links, or blocking negative effects of
AGE. Treatment of underlying pathologic states that accelerate AGE formation
(hyperglycemia, oxidative stress and hypoxia) is also important. Reducing exogenous
intake of AGE is a lifestyle modification in the treatment and prevention of diabetes and
obesity that will lower the risk of developing complications, and probably also lower
the risk of developing diabetes itself. The pathogenesis of type 2 diabetes is not yet fully
elucidated. AGE are implicated in the development of diabetes and its complications,
and anti-AGE therapies represent a novel category of therapeutic interventions against
diabetes.
Keywords: Diabetes, advanced glycation end products (AGE), retinopathy,
neuropathy, nephropathy, diabetes complications, receptor for AGE (RAGE),
methylglyoxal.