In T1D, deficiency of the secretory response of glucagon to hypoglycemia is an early acquired (<2 years of onset) abnormality of counter-regulation and leads to severe hypoglycemia (Cryer, 2002; Siafarikas et al., 2012), which may in part be explained by the major structural and functional changes that occur to islets in T1D. This evidence concerns the gene GCG and type 1 diabetes mellitus.