ADVANCED GLYCATION END PRODUCTS (AGEs) AND LATE COMPLICATIONS IN DIABETES

Abstract

The pathophysiological condition of hyperglycemia found in diabetic patients promotes significant changes in the metabolism of carbohydrates, proteins and lipids. The significant increase in the availability of glucose in the intracellular medium directly affects glucose metabolism by diverting some of its intermediates to alternative routes, generating elevated levels of end products that are normally produced in small amounts during normal metabolism.  The greatest impact of action as the body's response to hyperglycemia is the production of a class of heterogeneous molecules known as advanced glycation end products (AGEs). Persistent hyperglycemia results in progressive non-enzymatic glycation of intra- and extracellular components such as proteins, lipids, and nucleic acids, or AGEs, which play a central role in the late complications found in diabetes. Because they are located at the interface between blood and tissues, the endothelium plays an important role in the maintenance of systemic physiology, being extremely susceptible to pathogenic stimuli that lead to cellular senescence. Endothelial cells are secretors of pro-inflammatory cytokines, contributing to various cardiovascular and metabolic pathologies, mainly involving retinal hair cells, Schwann cells in peripheral nerves, renal glomerulus, and neurons. The accumulation of AGEs in cells causes abnormal glycation of proteins, leading to their misfolding and abnormal aggregation, as well as increasing oxidative stress and pro-inflammatory events. These events induce chronic complications in the micro- and microcirculation, resulting in progressive endothelial damage and are associated with capillary occlusion, ischemia, and organ failure.

DOI: https://doi.org/10.56238/sevened2025.013-005