title: Elimination of dietary gluten does not reduce titers of type 1 diabetes-associated autoantibodies in high-risk subjects.
abstract: OBJECTIVE
  Removal of the dietary wheat protein gluten protects against autoimmune diabetes in animal models. Furthermore, elimination of dietary gluten reduces the frequency of type 1 diabetes in patients with celiac disease. Herein we test the hypothesis that gluten is the driving antigen for type 1 diabetes-associated islet autoimmunity.
  
  
  METHODS
  Seven autoantibody-positive, first-degree relatives of patients with type 1 diabetes were placed on a gluten-free diet for 12 months followed by gluten reexposure for 12 months. Gliadin antibodies as well as the diabetes-related antibodies insulin autoantibody (IAA), GAD antibody (GADA), and tyrosin phosphatase IA2 antibody (IA-2A) were measured every 3 months; oral glucose tolerance tests were performed every 6 months. Changes in autoantibody titers were compared with those observed in a matched historical cohort.
  
  
  RESULTS
  A reduction in IgG gliadin antibody titers was observed during the gluten-free period, but titers of diabetes-associated autoantibodies changed independently of gluten exposure. Type 1 diabetes-associated islet autoantibody levels at the end of the gluten-free diet period were not significantly different from those before commencement of the diet (P = 0.2) or at the end of the gluten reexposure period (P = 0.4). Changes in individual subjects were identified, but no differences were noted between the gluten-free and the gluten re-exposure periods, and the changes were similar to those observed in the historical control cohort (P = 1.0). Major titer reductions (>50%) in the gluten-free period were observed in only one subject for all antibodies. Type 1 diabetes developed in this subject and in a second subject during the gluten reexposure period.
  
  
  CONCLUSIONS
  The findings do not support the hypothesis that gluten is a driving antigen in type 1 diabetes.
authors.affiliation: Diabetes Research Institute and 3rd Medical Department, Academic Teaching Hospital München-Schwabing, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Heike E
authors.initials: HE
authors.lastname: Naserke
authors.forename: Anette G
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D003927:Diet, Diabetic; D018450:Disease Progression; D005190:Family; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D005983:Glutens; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D023421:Models, Animal; D010349:Patient Compliance; D018579:Patient Selection; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; C024211:islet cell antibody; D005983:Glutens; D005968:Glutamate Decarboxylase