The Pathogenesis of Type-2-Diabetes Glycotoxicity and the Role of Carbohydrates

Type-2 diabetes is the result of insulin resistance, usually associated with obesity, and a progredient beta-cell failure. It is generally believed that b-cell dysfunction is caused by external factors, and three different noxious agents have been proposed: elevated blood glucose levels (,,glucotoxicity"), fatty acids and/or triglycerides accumulating in the beta-cells (,,lipotoxicity"), and inflammatory cytokines from adipose tissue. This review summarizes the available evidence for the glucotoxicity concept, in particular with regard to the role of dietary carbohydrates. The data are consistent with the hypothesis that postprandial glucose excursions are a major factor in the development of type-2 diabetes. However, a dietary intervention reducing the glycemic load is probably less effective in reducing the diabetes risk than a reduction of body fat.