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 of the advanced Maillard reaction - pyrraline, pentosidine and carboxymethyllysine - which can serve as markers for in vivo studies. Pyrraline is a glucose-derived compound, the presence of which was detected with 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 immediate precursor of pyrraline is 3-deoxyglucosone (3-DG), a product formed through degradation of glycated proteins. 3-DG is present in elevated levels in plasma and urine from diabetic humans. Pentosidine is a pentose-derived protein crosslink, which forms from glycated proteins in the presence of oxygen. Pentosidine increases ubiquitously in aging tissues, and at an accelerated rate in diabetes and especially in uraemia. Skin pentosidine levels correlate with the severity of diabetic complications in type I (insulin-dependent) diabetes. Its levels, like those of carboxymethyllysine, an Amadori fragmentation and oxidation product, are not reversible upon tight control of diabetes over a 4-month period. Assuming these advanced products reflect cumulative glycaemia over several years, it would appear that there is a correlation between the severity of complications and total exposure to glucose.