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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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 - 2004

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Medical problems
Type 1 Diabetes Mellitus
Insulin
C-Peptide
Islets of Langerhans
Autoantibodies
Therapeutics
Plasmas
Progression
Therapy
Diabetes
Age of Onset
Hypoglycemic Agents
Meals
Eating
Placebos
Cells
Dose

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

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ergun-Longmire, B., Marker, J., Zeidler, A., Rapaport, R., Raskin, P., Bode, B., ... 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

Oral insulin therapy to prevent progression of immune-mediated (Type 1) diabetes. / Ergun-Longmire, Berrin; Marker, John; Zeidler, Adina; Rapaport, Robert; Raskin, Philip; Bode, Bruce; Schatz, Desmond; Vargas, Alfonso; Rogers, Douglas; Schwartz, Sherwyn; Malone, John; Krischer, Jeffrey; Maclaren, Noel K.

In: Annals of the New York Academy of Sciences, Vol. 1029, 2004, p. 260-277.

Research output: Contribution to journalArticle

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, NK 2004, 'Oral insulin therapy to prevent progression of immune-mediated (Type 1) diabetes', Annals of the New York Academy of Sciences, vol. 1029, pp. 260-277. https://doi.org/10.1196/annals.1309.057
Ergun-Longmire, Berrin ; Marker, John ; Zeidler, Adina ; Rapaport, Robert ; Raskin, Philip ; Bode, Bruce ; Schatz, Desmond ; Vargas, Alfonso ; Rogers, Douglas ; Schwartz, Sherwyn ; Malone, John ; Krischer, Jeffrey ; Maclaren, Noel K. / Oral insulin therapy to prevent progression of immune-mediated (Type 1) diabetes. In: Annals of the New York Academy of Sciences. 2004 ; Vol. 1029. pp. 260-277.
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