Differential sensitivity to beta-cell secretagogues in "early," type I diabetes mellitus.

The insulin secretory response to various beta-cell secretagogues was studied in four children (ages 11, 11, 12, and 10 yr) in "early" stages or remission of type I diabetes mellitus. One child was an anti-islet antibody positive monozygotic twin of a type I diabetic subject, two children had impaired glucose tolerance and elevated levels of Ia-positive T-cells, and the fourth was in remission (off insulin) of type I diabetes 6 mo after immunotherapy. The peak first-phase (0-10 min) insulin increment after intravenous (i.v.) glucose was negligible in each patient, whereas the peak responses to i.v. glucagon, tolbutamide, arginine, and oral glucose ranged between 10% and 43% of median responses in normal control subjects. The rank order of response to a variety of secretagogues was remarkably similar in all four subjects: i.v. arginine greater than i.v. glucagon greater than oral glucose greater than i.v. tolbutamide greater than i.v. glucose. These studies indicate that a "functional" beta-cell defect, namely a complete loss of response to i.v. glucose and a partial loss to other secretagogues, exists in type I diabetic patients before complete beta-cell destruction. This alteration in beta-cell responsiveness probably underlies our prior observation of slowly progressive loss of i.v.-glucose-induced insulin release in islet cell antibody-positive siblings to type I diabetic subjects.