title: Oral insulin therapy to prevent progression of immune-mediated (type 1) diabetes.
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.
authors.affiliation: Division of Pediatric Endocrinology, New York-Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Berrin
authors.initials: B
authors.lastname: Ergun-Longmire
authors.forename: John
authors.initials: J
authors.lastname: Marker
authors.forename: Adina
authors.initials: A
authors.lastname: Zeidler
authors.forename: Robert
authors.initials: R
authors.lastname: Rapaport
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
authors.forename: Alfonso
authors.initials: A
authors.lastname: Vargas
authors.forename: Douglas
authors.initials: D
authors.lastname: Rogers
authors.forename: Sherwyn
authors.initials: S
authors.lastname: Schwartz
authors.forename: John
authors.initials: J
authors.lastname: Malone
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.forename: Noel K
authors.initials: NK
authors.lastname: Maclaren
mesh_terms: D000284:Administration, Oral; D001323:Autoantibodies / Q000627:therapeutic use; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; C024211:islet cell antibody