The trajectories for the different variables perceived as risk factors (Figure 2) showed an increase in IA-2A and ZnT8A titers (Panel G4 and I4), as well as glucose metabolism measures, like HbA1c (Panel E4), fasting glucose (Panel A4) and 2 h glucose (OGTT) (Panel B4) years prior to type 1 diabetes, reflecting a progressive autoimmune destruction of the pancreatic beta-cells leading to loss of beta cell function and an impaired insulin production [34, 35]. This evidence concerns the gene INS and type 1 diabetes mellitus.