Glycosylation products as toxic mediators of diabetic complications.

Hyperglycemia causes excessive amounts of irreversible advanced glycosylation end products (AGEPs) to accumulate on long-lived extracellular matrix proteins and probably also on DNA in tissues that develop diabetic complications. AGEPs induce permanent abnormalities in extracellular protein cross-linking, cell-matrix interactions, and DNA structure in vitro. Pharmacologically inhibiting AGEP formation in long-term diabetic animals prevents both retinal capillary pathology and thickening of the glomerular basement membrane.