Oral insulin therapy to prevent progression of immune-mediated (Type 1) diabetes

Berrin Ergun-Longmire, John Marker, Adina Zeidler, Robert Rapaport, Philip Raskin, Bruce Bode, Desmond Schatz, Alfonso Vargas, Douglas Rogers, Sherwyn Schwartz, John Malone, Jeffrey Krischer, Noel K. Maclaren

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46 Scopus citations

Abstract

Repeated ingestion of insulin has been suggested as an immune tolerization therapy to prevent immune-mediated (type 1) diabetes. We performed a placebo-controlled, two-dose, oral insulin tolerance trial in newly diagnosed (<2 years) diabetic patients who had required insulin replacement for less than 4 weeks and were found to have cytoplasmic islet cell autoantibodies (ICAs). No oral hypoglycemic agents were permitted during the trial. Endogenous insulin reserves were estimated at six-month intervals by plasma C-peptide responses to a mixed meal. Positive ICAs were found in 262 (31%) of the 846 patients screened. Of the 197 who agreed to participate, 187 could be followed for 6 to 36 months. Endogenous insulin retention was dependent upon initial stimulated C-peptide response, age at diabetes onset, and numbers of specific islet cell autoantibodies found. Oral insulin improved plasma C-peptide responses in patients diagnosed at ages greater than 20 years, best seen at the low (1 mg/day) over the high (10 mg/day) insulin dose (P = .003 and P = .01, respectively). In patients diagnosed before age 20 years, the 1 mg dose was ineffective, whereas the 10 mg dose actually accelerated C-peptide loss (P = .003). There were no adverse effects. If confirmed, these findings suggest that diabetic patients over age 20 years with ICA evidence of late-onset immune-mediated diabetes should be considered for oral insulin at 1 mg/day to better retain endogenous insulin secretion.

Original languageEnglish (US)
Pages (from-to)260-277
Number of pages18
JournalAnnals of the New York Academy of Sciences
Volume1029
DOIs
StatePublished - Jan 1 2004

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Keywords

  • Endogenous insulin reserve
  • GAD
  • HLA-DR/DQ phenotypes
  • IA-2 autoantibodies
  • Immune-mediated diabetes
  • Insulin antoantibodies
  • Islet cell autoantibodies (ICA)
  • Mixed meal tolerance testing
  • Oral insulin tolerance therapy
  • Type 1 diabetes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Ergun-Longmire, B., Marker, J., Zeidler, A., Rapaport, R., Raskin, P., Bode, B., Schatz, D., Vargas, A., Rogers, D., Schwartz, S., Malone, J., Krischer, J., & Maclaren, N. K. (2004). Oral insulin therapy to prevent progression of immune-mediated (Type 1) diabetes. Annals of the New York Academy of Sciences, 1029, 260-277. https://doi.org/10.1196/annals.1309.057