ABSTRACT
In this review, we bring our personal experiences to showcase insulin from its breakthrough discovery as a life-saving drug 100 years ago to its uncovering as the autoantigen and potential cause of type 1 diabetes and eventually as an opportunity to prevent autoimmune diabetes. The work covers the birth of insulin to treat patients, which is now 100 years ago, the development of human insulin, insulin analogues, devices, and the way into automated insulin delivery, the realization that insulin is the primary autoimmune target of type 1 diabetes in children, novel approaches of immunotherapy using insulin for immune tolerance induction, the possible limitations of insulin immunotherapy, and an outlook how modern vaccines could remove the need for another 100 years of insulin therapy. eTOC blurb Ziegler et al. showcase insulin from its breakthrough discovery as a life-saving drug 100 years ago to its uncovering as the autoantigen and potential cause of type 1 diabetes and eventually as a target of future immunotherapies to prevent autoimmune diabetes.