Two T1D endotypes have been defined; Endotype 1 is defined by early diagnosis, extensive beta-cell destruction, aggressive insulitis of both B and T cells [26], and aberrant proinsulin processing [27], whereas Endotype 2 is defined by later diagnosis, retention of residual insulin-containing islets, fewer infiltrating B and T cells, and normal proinsulin processing [27]. This evidence concerns the gene INS and type 1 diabetes mellitus.