ADVANCED MAILLARD REACTION-PRODUCTS AS MARKERS FOR TISSUE-DAMAGE IN DIABETES AND UREMIA - RELEVANCE TO DIABETIC NEPHROPATHY

Recent work has led to the structural elucidation of three compounds o f the advanced Maillard reaction - pyrraline, pentosidine and carboxym ethyllysine - which can serve as markers for in vivo studies. Pyrralin e is a glucose-derived compound, the presence of which was detected wi th a monoclonal antibody in elevated amounts in the plasma of diabetic individuals and rodents and in histological sections of renal tissue, especially in sclerosed glomerular and arteriolar regions. The immedi ate precursor of pyrraline is 3-deoxyglucosone (3-DG), a product forme d through degradation of glycated proteins. 3-DG is present in elevate d levels in plasma and urine from diabetic humans. Pentosidine is a pe ntose-derived protein crosslink, which forms from glycated proteins in the presence of oxygen. Pentosidine increases ubiquitously in aging t issues, and at an accelerated rate in diabetes and especially in uraem ia. Skin pentosidine levels correlate with the severity of diabetic co mplications in type I (insulin-dependent) diabetes. Its levels, like t hose of carboxymethyllysine, an Amadori fragmentation and oxidation pr oduct, are not reversible upon tight control of diabetes over a 4-mont h period. Assuming these advanced products reflect cumulative glycaemi a over several years, it would appear that there is a correlation betw een the severity of complications and total exposure to glucose.