Differential Sensitivity to β-Cell Secretagogues in “Early,” Type I Diabetes Mellitus
- Om P Ganda,
- S Srikanta,
- Stuart J Brink,
- Mary Ann Morris,
- Ray E Gleason,
- J Stuart Soeldner and
- George S Eisenbarth
- 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
- Address reprint requests to George S. Eisenbarth, MD., Ph.D., Joslin Diabetes Center, Research Division, One Joslin Place, Boston, Massachusetts 02215.
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.
- Copyright © 1984 by the American Diabetes Association