INS and type 1 diabetes mellitus: It is suggested that combined affect of INSI/I and CTLA4G/G genotype in older children with type 1 diabetes is related to time of puberty as during puberty immune response and hormonal requirements are at high levels.[12] The explanation for children having the combined INS I/I and CTLA4 G/G genotype, develops type 1 diabetes at a later age of onset involve insulin requirements and the immune response, both of which are at their peak during puberty.