Immunobiology of beta-cell destruction.

Type 1 diabetes is a chronic disease characterized by severe insulin deficiency and hyperglycemia, due to autoimmune destruction of pancreatic islets of Langerhans. A susceptible genetic background is necessary, but not sufficient, for the development of the disease. Epidemiological and clinical observations underscore the importance of environmental factors as triggers of type 1 diabetes, currently under investigation. Islet-specific autoantibodies precede clinical onset by months to years and are established tools for risk prediction, yet minor players in the pathogenesis of the disease. Many efforts have been made to elucidate disease-relevant defects in the key immune effectors of islet destruction, from the early failure of specific tolerance to the vicious circle of destructive insulitis. However, the events triggering islet autoimmunity as well as the transition to overt diabetes are still largely unknown, making prevention and treatment strategies still a challenge.