INS and type 1 diabetes mellitus: The primacy of the immune response to insulin and its precursors in the etiology of T1D is evident from the fact that IAA is often the earliest autoantibody to appear in children destined to be diagnosed with T1D [16,44]; in contrast to other autoantibodies that appear before diagnosis of T1D, mean IAA levels predict age-at-diagnosis [17-19]; and a polymorphism just 5' of the structural gene, insulin, regulates its transcription in thymus and alters risk of T1D [45].