title: High frequency of abnormal glucose tolerance in DQA1*0102/DQB1*0602 relatives identified as part of the Diabetes Prevention Trial--Type 1 Diabetes.
abstract: OBJECTIVE
  Immunological and genetic markers can be used to assess risk of developing type 1 diabetes prior to the onset of clinical symptoms. Autoantibody-positive relatives of patients with type 1 diabetes are at increased risk for disease, while the presence of HLA DQA1*0102/DQB1*0602 is thought to confer protection. Using the unique population identified by the Diabetes Prevention Trial--Type Diabetes (DPT-1), our aim was to determine if these individuals were protected from type 1 diabetes.
  
  
  METHODS
  We described metabolic and immunological characteristics of islet cell cytoplasmic autoantibodies-positive relatives with DQB1*0602 identified as part of DPT-1.
  
  
  RESULTS
  We found that 32% of DQB1*0602-positive relatives identified through the DPT-1 had abnormalities of glucose tolerance despite the fact that only 19% had multiple type 1 diabetes-associated autoantibodies and only 13% had abnormal insulin secretion, markers typically associated with the disease. In addition, these markers were not associated with abnormal glucose tolerance. In contrast, the DQB1*0602-positive relatives had elevated fasting insulin (117+/-10 pmol/l) and homeostasis model assessment of insulin resistance (HOMA-R) (4.90+/-0.5) values, which are more commonly associated with type 2 diabetes. The later marker of insulin resistance was associated with glucose tolerance status.
  
  
  CONCLUSIONS
  Our data indicate that DQA1*0102/DQB1*0602 relatives identified through DPT-1 have a high frequency of abnormal glucose tolerance and a disease phenotype with characteristics of type 1 and type 2 diabetes. Thus, multiple pathways to abnormal glucose tolerance are present within families of these type 1 patients.
authors.affiliation: Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA 98101, USA. cjgreen@benaroyaresearch.org
authors.forename: C J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: G
authors.initials: G
authors.lastname: Eisenbarth
authors.forename: M
authors.initials: M
authors.lastname: Atkinson
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: S
authors.initials: S
authors.lastname: Babu
authors.forename: D
authors.initials: D
authors.lastname: Schatz
authors.forename: A
authors.initials: A
authors.lastname: Zeidler
authors.forename: T
authors.initials: T
authors.lastname: Orban
authors.forename: C
authors.initials: C
authors.lastname: Wasserfall
authors.forename: D
authors.initials: D
authors.lastname: Cuthbertson
authors.forename: J
authors.initials: J
authors.lastname: Krischer
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D018149:Glucose Intolerance / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005951:Glucose Tolerance Test; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen