title: Oral insulin administration and residual beta-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial. Diabète Insuline Orale group.
abstract: BACKGROUND
  Oral administration of autoantigens can slow the progression of beta-cell destruction in non-obese diabetic mice. We investigated whether oral administration of recombinant human insulin could protect residual beta-cell function in recent-onset type 1 diabetes.
  
  
  METHODS
  We enrolled 131 autoantibody-positive diabetic patients aged 7-40 years within 2 weeks of diagnosis (no ketoacidosis at diagnosis, weight loss <10%, polyuria for <6 weeks). They were randomly assigned 2.5 mg or 7.5 mg oral insulin daily or placebo for 1 year, in addition to subcutaneous insulin therapy. Serum C-peptide concentrations were measured in the fasting state and after stimulation, to assess beta-cell function. Autoantibodies to beta-cell antigens were assayed. Analyses were by intention to treat.
  
  
  RESULTS
  Baseline C-peptide and haemoglobin A1c concentrations were similar in the three groups. During follow-up, there were no differences between the groups assigned 2.5 mg or 7.5 mg oral insulin or placebo in subcutaneous insulin requirements, haemoglobin A1c concentrations, or measurements of fasting (mean at 12 months 0.18 [SD 0.17], 0.17 [0.17], and 0.17 [0.12] nmol/L) or stimulated C-peptide concentrations (glucagon-stimulated 0.39 [0.38], 0.37 [0.39], and 0.33 [0.24] nmol/L; meal-stimulated 0.72 [0.60], 0.49 [0.49], and 0.57 [0.51 nmol/L]. Neither age nor C-peptide concentration at entry influenced treatment effects. No differences were seen in the time-course or titres of antibodies to insulin, glutamic acid decarboxylase, or islet antigen 2.
  
  
  CONCLUSIONS
  At the doses used in this trial, oral administration of insulin initiated at clinical onset of type 1 diabetes did not prevent the deterioration of beta-cell function.
authors.affiliation: Centres Hospitaliers Universitaires de Nantes, France. lucy.chaillous@wanadoo.fr
authors.forename: L
authors.initials: L
authors.lastname: Chaillous
authors.forename: H
authors.initials: H
authors.lastname: Lefèvre
authors.forename: C
authors.initials: C
authors.lastname: Thivolet
authors.forename: C
authors.initials: C
authors.lastname: Boitard
authors.forename: N
authors.initials: N
authors.lastname: Lahlou
authors.forename: C
authors.initials: C
authors.lastname: Atlan-Gepner
authors.forename: B
authors.initials: B
authors.lastname: Bouhanick
authors.forename: A
authors.initials: A
authors.lastname: Mogenet
authors.forename: M
authors.initials: M
authors.lastname: Nicolino
authors.forename: J C
authors.initials: JC
authors.lastname: Carel
authors.forename: P
authors.initials: P
authors.lastname: Lecomte
authors.forename: R
authors.initials: R
authors.lastname: Maréchaud
authors.forename: P
authors.initials: P
authors.lastname: Bougnères
authors.forename: B
authors.initials: B
authors.lastname: Charbonnel
authors.forename: P
authors.initials: P
authors.lastname: Saï
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D007330:Insulin Antibodies / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin; D007330:Insulin Antibodies; D011994:Recombinant Proteins