The increased frequency of extra-islet glucagon-positive cells in T1D is noteworthy, and the frequency is considerably higher compared to what has been previously reported for islets (median 53.0 extra-islet cells/mm2 in T1D, median 11.2 extra-islet cells/mm2 in controls, and median 4.4 islets/mm2 in control subjects) [14]. This evidence concerns the gene GCG and type 1 diabetes mellitus.