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Oral Insulin Therapy to Prevent Progression of Immune‐Mediated (Type 1) Diabetes
Author(s) -
ERGUNLONGMIRE 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.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1309.057
Subject(s) - insulin , medicine , diabetes mellitus , endocrinology , placebo , type 1 diabetes , autoantibody , c peptide , islet , type 2 diabetes , immune system , adverse effect , endogeny , immunology , antibody , alternative medicine , pathology
A bstract : 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.