MAILLARD REACTION-PRODUCTS AND THEIR RELATION TO COMPLICATIONS IN INSULIN-DEPENDENT DIABETES-MELLITUS

Glycation, oxidation, and browning of proteins have all been implicate d in the development of diabetic complications. We measured the initia l Amadori adduct, fructoselysine (FL); two Maillard products, N(epsilo n)-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (exc itation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 d iabetic patients (aged 41.5 +/- 15.3 117-731 yr; duration of diabetes 17.9 +/- 11.5 10-461 yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16 ) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] greater-than-or-equal-to 20 mug/min; n = 9); and limited joint mobilit y (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased prog ressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were a lso elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regr ession, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.011. 12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nep hropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P < 0.05; CML OR = 13.44,9 5% CI = 2.0093. 30, P < 0.01). The associations between fluorescence a nd retinopathy and between pentosidine and nephropathy approached sign ificance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and sugg est that protein glycation and oxidation (glycoxidation) may be implic ated in the development of diabetic retinopathy and early nephropathy.