Differential Sensitivity to β-Cell Secretagogues in “Early,” Type I Diabetes Mellitus

  1. George S Eisenbarth
  1. E. P. Joslin Research Laboratory and the Joslin Clinic, Brigham and Women's Hospital; and New England Deaconess Hospital, Department of Medicine, Harvard Medical School Boston, Massachusetts Duke University Medical Center Durham, North Carolina
  1. Address reprint requests to George S. Eisenbarth, MD., Ph.D., Joslin Diabetes Center, Research Division, One Joslin Place, Boston, Massachusetts 02215.

Abstract

The insulin secretory response to various β-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 la-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 > i.v. glucagon > oral glucose > i.v. tolbutamide > i.v. glucose. These studies indicate that a “functional” β-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 β-cell destruction. This alteration in β-cell responsiveness probably underlies our prior observation of slowly progressive loss of i.v.-glucose-induced insulin release in islet cell antibody-positive siblings of type I diabetic subjects.

  • Received July 18, 1983.
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