Fatal Attraction: Interactions between antigen-presenting cells and islets of Langerhans in the pathogenesis of autoimmune diabetes

The onset of diabetes mellitus is characterized by various symptoms, all the result of\\na disturbed glucose metabolism. The main symptoms are thirst and an excessive production\\nof urine. The disturbed glucose metabolism underlying these symptoms is due to an absolute\\ndeficiency of insulin secretion (type 1 diabetes mellitus), a reduction in its biological effectiveness\\n(type 2 diabetes mellitus) or a combination of these factors. Type 1 diabetes mellitus\\nis predominantly manifesting in children, and needs to be treated by life-long exogenous\\ninsulin administration to prevent high blood glucose levels. Type 2 diabetes mellitus occurs\\nclassically in adults, and is relatively milder in its appearance; usually, exogenous insulin\\nadministration is not required. This thesis concerns type 1 (insulin-dependent) diabetes mellitus\\n(type I diabetes).\\nIn the Netherlands, the annual incidence of type I diabetes among children younger\\nthan 14 years was 14.3 per 100,000 in the period from 1993\\xc2\\xb71995. Compared to earlier studies, the incidence has increased and the clinical manifestation has shifted to younger ages.\\nAlthough the possibility of exogenous insulin administration has largely reduced the risk for\\nshort-term complications, such as diabetic ketoacidosis and hyperglycaemic coma, over 70%\\nof patients will develop long-tenn complications. These include microangiopathy, that may\\ncause problems with the kidney-function and the vision, and macropangiopathy, that leads to\\nan elevated risk of developing major cardiovascular problems. The quality of life of diabetes\\npatients can be profoundly reduced because of these complications. In addition, the lifeexpectancy\\nof diabetes patients is considerably shorter than that of healthy persons. The risk\\nof developing long-term complications may be signiticantly reduced by normalizing blood\\nglucose levels. However, this requires intensive individual treatment and significant changes\\nin lifestyle. Consequently, the disease has large emotional and social impact on the lifes of\\npatients and their family. In addition, diabetes has serious economic consequences, because\\nof the costs of the treatment and lost productivity due to hospital admission.\\nTherefore, prevention and cure of the disease are major goals of diabetes research.\\nIn order to achieve these goals, a thorough knowledge is required about the mechanisms via\\nwhich diabetes develops. The studies described in this thesis describe such a mechanism.