Diminished A-cell secretion in the early phase of type I diabetes mellitus

The A-cell function in "true pre-type I diabetes" or in early phase of type I diabetes has not been reported. We studied A-cell reserve in response to intravenous arginine infusion in six individuals characterized by type I diabetes-associated immunologic defects and absent first-phase insulin secretory response to intravenous glucose prior to development of diabetes. The peak glucagon response in these patients was markedly impaired (153 +/- 39 pg/mL, mean +/- SEM) compared to a group of 23 normal, healthy controls (301 +/- 18; P less than 0.01) and a group of 11 healthy, discordant monozygotic twins of type I diabetic patients (250 +/- 25, P less than 0.05). The glucagon concentrations in response to oral glucose were completely suppressed to undetectable levels in three of the patients studied. In view of the well-known observations of insulitis in the prediabetic phase in man and in experimental models of type I diabetes and anti-islet cytoplasmic antibodies directed against all islet cells, our observations suggest an impairment of A-cells during the evolution of type I diabetes.