title: High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes.
abstract: OBJECTIVE
  The aim of the present study was to define heterogeneity of adult-onset autoimmune diabetes based on characterization of GAD antibodies (GADAs).
  
  
  METHODS
  Patients enrolled in a nationwide survey, the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study, have been screened for GADAs and IA-2 antibodies (IA-2As) and further characterized for GADA titer, antibodies to thyroid peroxidase (TPO), and HLA DRB1-DQB1 polymorphisms.
  
  
  RESULTS
  Of 4,250 consecutive type 2 diabetic patients, 4.5% had either GADAs and/or IA-2As. Patients with autoimmune diabetes showed a clinical phenotype significantly different from that of type 2 diabetes, including higher fasting glucose and A1C, lower BMI and uric acid, lower prevalence of metabolic syndrome and its components, and higher frequency of TPO antibodies. More interestingly, analysis of GADA titers showed a bimodal distribution that identified two subgroups of patients with high (>32 GADA arbitrary units) and low (< or =32 GADA arbitrary units) GADA titers. Compared with those with low GADA titers, patients with high GADA titers had more prominent traits of insulin deficiency and a profile of more severe autoimmunity resulting in higher A1C, lower BMI, a lower prevalence of metabolic syndrome and its components (P < 0.02 for all), a higher prevalence of IA-2As, TPO antibodies (P < 0.003 for both), and DRB1*03-DQB1*0201 (50 vs. 26.8%, P = 0.001), and a decreasing frequency of DQB1*0602 and DRB1*0403 (from type 2 to low and to high GADA titer autoimmune diabetes; P < 0.001 for trend for both comparisons).
  
  
  CONCLUSIONS
  GADA titers identify two subgroups of patients with adult-onset autoimmune diabetes having distinct clinical, autoimmune, and genetic features.
authors: Department of Clinical Sciences, La Sapienza University, Rome, Italy. raffaella.buzzetti@uniroma1.it
authors: Raffaella
authors: R
authors: Buzzetti
authors: Sergio
authors: S
authors: Di Pietro
authors: Andrea
authors: A
authors: Giaccari
authors: Antonio
authors: A
authors: Petrone
authors: Mattia
authors: M
authors: Locatelli
authors: Concetta
authors: C
authors: Suraci
authors: Marco
authors: M
authors: Capizzi
authors: Maria Luisa
authors: ML
authors: Arpi
authors: Elena
authors: E
authors: Bazzigaluppi
authors: Francesco
authors: F
authors: Dotta
authors: Emanuele
authors: E
authors: Bosi
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000172:deficiency; D007558:Italy; D010641:Phenotype
chemical_list: D001323:Autoantibodies; D007328:Insulin; D005968:Glutamate Decarboxylase