In addition, the TN-07 trial demonstrated that stage 2 individuals with a low first phase insulin response were better responders to oral insulin therapy (17), whereas attempts to administer therapy at earlier stages in autoantibody negative, high-risk children aged 6 months to 3 years did not show any difference compared to placebo (18), suggesting that initiating antigen-specific immunotherapy in the later stage of pre-diabetes (stage 2; autoantibody positivity and metabolic dysfunction) holds the potential of a better therapeutic response. This evidence concerns the gene INS and diabetes mellitus.