INS and type 2 diabetes mellitus: In addition, several studies have shown that the effect of rs1044498 and rs2295490 is more evident on early-onset T2D [26, 28, 104]; notably similar data have been obtained for rs1801278 of IRS1 gene [106]; these data hint to the possibility that focusing on early-onset cases may represent a successful strategy to study the contribution of insulin-signaling gene variants to T2D pathogenesis.