DIFFERENTIAL-EFFECTS OF TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS ON PENTOSIDINE FORMATION IN SKIN AND GLOMERULAR-BASEMENT-MEMBRANE

Pentosidine is an advanced Maillard/glycation reaction product the for mation of which in human skin is significantly increased in Type 1 (in sulin-dependent) diabetes mellitus and correlates with the severity of diabetic complications. Preliminary data in a limited number of Type 2 (non-insulin-dependent) diabetic individuals showed that skin pentos idine was not significantly elevated, raising the question of whether statistical power was insufficient for differences to be revealed, or whether pentosidine did not form because biological factors intrinsic to Type 2 diabetes affected the advanced Maillard reaction altogether. To resolve this question, pentosidine levels were measured in 209 hum an skin samples obtained at autopsy and in purified glomerular basemen t membranes from 45 subjects of various ages, with and without Type 1 and Type 2 diabetes and uraemia. Pentosidine increased exponentially i n skin but curvilinearly in glomerular basement membranes, and reached 75 and 50 pmol/mg collagen at projected 100 years, respectively. Skin levels were not significantly elevated in individuals with Type 2 dia betes (p > 0.05). In contrast, pentosidine levels in glomerular baseme nt membranes were elevated above the 95 % confidence interval in the m ajority of diabetic patients regardless of the type of diabetes and in all individuals on haemodialysis. These data clearly demonstrate that the advanced Maillard reaction is indeed accelerated in Type 2 diabet es and strongly suggest that differences in pentosidine accumulation r ates may be due to differences in collagen turnover. In diabetes and U raemia, accelerated Maillard reaction mediated protein crosslinking, a s reflected by pentosidine, may contribute to decreased turnover of th e extracellular matrix, sclerosis and thickening of basement membranes .