Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus

• Published in: The Journal of clinical investigation 1993-06, Vol.91 (6), p.2470-2478
• Main Authors: MCCANCE, D. R, DYER, D. G, DUNN, J. A, BAILIE, K. E, THORPE, S. R, BAYNES, J. W, LYONS, T. J
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arginine - analogs & derivatives; Arginine - analysis; Associated diseases and complications; Biological and medical sciences; Collagen - chemistry; Diabetes Mellitus, Type 2 - complications; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - complications; Diabetic Nephropathies - complications; Diabetic Retinopathy - complications; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Humans; Lysine - analogs & derivatives; Lysine - analysis; Maillard Reaction; Male; Medical sciences; Microcirculation - physiopathology; Middle Aged; Skin - chemistry
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI116482

Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 [17-73] yr; duration of diabetes 17.9 +/- 11.5 [0-46] 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] > or = 20 micrograms/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were also 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 regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P < 0.05; CML OR = 13.44, 95% CI = 2.00-93.30, P < 0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy.