INCREASED COLLAGEN-LINKED PENTOSIDINE LEVELS AND ADVANCED GLYCOSYLATION END-PRODUCTS IN EARLY DIABETIC NEPHROPATHY

Rationale: Advanced glycosylation end products (AGEs) may play an impo rtant role in the development of diabetic vascular sequelae. An AGE cr oss-link, pentosidine, is a sensitive and specific marker for tissue l evels of AGEs. Objectives: To evaluate the role of AGEs in the develop ment of diabetic nephropathy and retinopathy, we studied pentosidine l evels and the clinical characteristics of 48 subjects with insulin-dep endent diabetes mellitus. Diabetic nephropathy was classified as norma l, microalbuminuria, or gross proteinuria, and retinopathy was graded as none, background, or proliferative. Newly observed findings: Signif icant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03+/-9.47 vs 76.46+/-6.37 pm ol/mg col) when compared with normal (56.96+/-3.26 pmol/mg col). Multi variate analysis to correct for age, duration of diabetes, and gender did not modify the results. Elevated pentosidine levels were also foun d in those with proliferative when compared with those with background retinopathy (75.86+/-5.66 vs 60.42+/-5.98 pmol/mg col) (P < 0.05). Co nclusions: Microalbuminuria is associated with elevated levels of pent osidine similar to those found in overt diabetic nephropathy suggestin g that elevated AGE levels are already present during the earliest det ectable phase of diabetic nephropathy.