The significance of the products of the Maillard (browning) reaction in diabetes.

The accumulation of the products of the Maillard reaction leads to structural and functional modifications of tissue proteins. In normoglycaemia, these modifications result in slow age-related accumulation of AGE-proteins. Hyperglycaemia accelerates formation of the Maillard products. The increased rate of Amadori products formation in poorly controlled diabetes leads to the impairment of the function of susceptible short-lived proteins and accelerates the formation of AGE on proteins with a long half-life. AGE accumulation increases protein crosslinking and leads to changes in the mechanical and biological properties of the affected proteins. AGE-modified proteins covalently bind other molecules. This may contribute to the formation of pathological tissue deposits and to the in situ formation of immune complexes. AGE-modified proteins also induce changes in biosynthetic/secretory patterns of macrophages, endothelial cells, and mesangial cells. These data led to the formulation of hypotheses which propose a central role for the Maillard products both in the process of ageing and in the development of the late complications of diabetes. More clinical studies are required to further substantiate these attractive hypotheses.