INS and type 1 diabetes mellitus: The earlier and more profound effect in type 1 diabetes and the association with C-peptide levels suggest loss of regulatory beta cell signals, such as zinc, insulin or γ-aminobutyric acid (GABA) [17], but direct effects of glucose [17] or paracrine signals, such as basal hypersecretion of somatostatin, may also explain the loss of physiological glucagon [18].