Type I diabetes mellitus is a chronic autoimmune disease in which there is T cell-mediated destruction of the pancreatic beta cells. Susceptibility to the disease is determined by several genes, with HLA genes having the strongest effect. The onset of the disease is predictable, at least in the relatives of affected persons, using a combination of autoantibody measurements, intravenous glucose tolerance testing, and genetic typing. The disease may be preventable, and several large clinical trials are now underway to test whether interventions such as administering low-dose insulin or the use of nicotinamide can prevent the onset of diabetes in at-risk relatives.