Insulin-dependent diabetes mellitus (IDDM) affects close to one million people in the United States. It is an autoimmune disease in which the immune system produces antibodies that attack the body's own insulin-manufacturing cells in the pancreas. Patients require daily injections of insulin to regulate blood sugar levels. The invention identified two proteins, named IA-2 and IA-2beta, that are important markers for type I (juvenile, insulin-dependent) diabetes. IA-2/IA-2beta, when used in diagnostic tests, recognized autoantibodies in 70 percent of IDDM patients. Combining IA-2/IA-2beta with other known markers increased the level of identification to 90 percent of individuals with IDDM. Moreover, the presence of autoantibodies to IA-2/IA-2beta in otherwise normal individuals was highly predictive in identifying those at risk of ultimately developing clinical disease. It is now possible to develop a rapid and effective test that can screen large populations for IDDM. In addition, IA-2/IA-2beta are candidates for immune tolerance and prevention of disease development.