ACCUMULATION OF MAILLARD REACTION-PRODUCTS IN SKIN COLLAGEN IN DIABETES AND AGING

To investigate the contribution of glycation and oxidation reactions t o the modification of insoluble collagen in aging and diabetes, Mailla rd reaction products were measured in skin collagen from 39 type 1 dia betic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the g lycoxidation products, N(epsilon)-(carboxymethyl)lysine (CML) and pent osidine, formed during later Maillard reactions. Collagen-linked fluor escence was also studied. In nondiabetic subjects, glycation of collag en (FL content) increased only 33% between 20 and 85 yr of age. In con trast, CML, pentosidine and fluorescence increased five-fold, correlat ing strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly wi th glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with c ontrol patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, p roviding evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabete s. These results support the description of diabetes as a disease char acterized by accelerated chemical aging of long-lived tissue proteins.