Vaccination against type 1 diabetes

Larsson HE, Lernmark A (Lund University/CRC, Skane University Hospital SUS, Malmo, Sweden). Vaccination against type 1 diabetes (Foresight). J Intern Med 2011; 269: 626-635. The clinical onset of type 1 diabetes or autoimmune diabetes occurs after a prodrome of islet autoimmunity. The warning signals for the ensuing loss of pancreatic islet beta cells are autoantibodies against insulin, GAD65, IA-2 and ZnT8, alone or in combinations. Autoantibodies against, for example, insulin alone have only a minor risk of type 1 diabetes. However, progression to clinical onset is increased by the induction of multiple islet autoantibodies. At the time of clinical onset, insulitis may be manifest, which seems to reduce the efficacy of immunosuppression. Autoantigen-specific immunotherapy with alum-formulated GAD65 (Diamyd (R)) shows promise to reduce the loss of beta-cell function after the clinical onset of type 1 diabetes. The mechanisms are unclear but may involve the induction of T regulatory cells, which may suppress islet autoantigen reactivity. Past and ongoing clinical trials have been safe. Future clinical trials, perhaps as combination autoantigen-specific immunotherapy, may increase the efficacy in preventing the clinical onset in subjects with islet autoantibodies or preserve residual beta-cell function in patients newly diagnosed with type 1 diabetes.