High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes

Raffaella Buzzetti, Sergio Di Pietro, Andrea Giaccari, Antonio Petrone, Mattia Locatelli, Concetta Suraci, Marco Capizzi, Maria Luisa Arpi, Elena Bazzigaluppi, Francesco Dotta, Emanuele Bosi

Research output: Contribution to journalArticle

Abstract

OBJECTIVE - The aim of the present study was to define heterogeneity of adult-onset autoimmune diabetes based on characterization of GAD antibodies (GADAs). RESEARCH DESIGN AND 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 (≤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.

Original languageEnglish
Pages (from-to)932-938
Number of pages7
JournalDiabetes Care
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Buzzetti, R., Di Pietro, S., Giaccari, A., Petrone, A., Locatelli, M., Suraci, C., Capizzi, M., Arpi, M. L., Bazzigaluppi, E., Dotta, F., & Bosi, E. (2007). High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. Diabetes Care, 30(4), 932-938. https://doi.org/10.2337/dc06-1696