Prediction and prevention of type 1 diabetes

Clinical type 1 diabetes represents end-stage insulitis resulting from progressive P-cell destruction over an asymptomatic period that may last for years. This knowledge and recent advances in our ability to identify individuals at increased risk for clinical disease have paved the way for trials aimed at preventing or delaying the clinical onset of type 1 diabetes. Individuals at risk for type 1 diabetes can be identified by a positive family history, or by genetic, immunological or metabolic markers. These markers can also be combined to achieve a higher positive predictive value. As long as there is no effective preventive modality available for clinical use, screening for the identification of risk individuals can be considered ethically acceptable only in the context of sound research protocols. Prevention of type 1 diabetes can be implemented at three different levels, out of which primary prevention includes all strategies aimed at decreasing the risk of developing type 1 diabetes in individuals without any signs of P-cell damage. Secondary prevention aims to reduce the incidence of type 1 diabetes by stopping P-cell destruction in individuals with signs of such a process, while the objective of tertiary prevention is to restore P-cell function or prevent complications in patients with overt type 1 diabetes. At present, one primary prevention trial and four comprehensive secondary prevention trials are in progress. Common features of these intervention trials are that the recruitment of patients fulfilling the inclusion criteria is time-consuming and the trials must proceed for a long time, as clinical disease is the end point. The secondary prevention trials also require extensive screening for the identification of eligible patients. The ongoing intervention trials may, however, represent a new era in type 1 diabetes, i.e. the beginning of the end of this complicated disease.