On the other hand, Smith et al. [18] reported that using an increased insulin dose calculated as 125% of the ICR for high-fat and protein meals was safe in children and adolescents with T1DM using the MDI regimen without any increase in the risk of hypoglycemia whether the additional insulin was given before the meal or as an additional dose 1 hr after the meal. This evidence concerns the gene INS and type 1 diabetes mellitus.