HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buzzetti, R. Search for Related Content PubMed PubMed Citation Articles by Buzzetti, R. Social Bookmarking                What's this?

High Titer of Autoantibodies to GAD Identifies a Specific Phenotype of Adult-Onset Autoimmune Diabetes

¹ Department of Clinical Sciences, "La Sapienza" University, Rome, Italy
² Diabetes Unit Instituto Nazionale Riposo e Cura Anziani (INRCA), Rome, Italy
³ Endocrinology, Catholic University, Rome, Italy
⁴ Bambino Gesù Hospital, Rome, Italy
⁵ Sandro Pertini Hospital, Rome, Italy
⁶ Endocrinology, Garibaldi di Nesima Hospital, Catania University, Catania, Italy
⁷ General Medicine, Diabetes and Endocrinology, San Raffaele Vita-Salute University, Milan, Italy
⁸ Department of Internal Medicine, Siena University, Siena, Italy

Address correspondence and reprint requests to Prof. Raffaella Buzzetti, MD, Azienda Policlinico Umberto I, Viale del Policlinico 155, 00161 Roma, Italy. E-mail: raffaella.buzzetti{at}uniroma1.it

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.

Abbreviations: GADA, GAD antibody • IA-2A, IA-2 antibody • ICA, islet cell antibody • NIRAD, Non Insulin Requiring Autoimmune Diabetes • TPO, thyroid peroxidase • U, arbitrary units

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Maruyama, S. Oak, A. Shimada, and C. S. Hampe GAD65 Autoantibody Responses in Japanese Latent Autoimmune Diabetes in Adult Patients Diabetes Care, August 1, 2008; 31(8): 1602 - 1607. [Abstract] [Full Text] [PDF]

				H Davies, S. Mannan, S Brophy, and R Williams Routine glutamic acid decarboxylase autoantibody (GADA) testing: patients' perspective Fam. Pract., June 1, 2008; 25(3): 176 - 180. [Abstract] [Full Text] [PDF]

				C. Tiberti, C. Giordano, M. Locatelli, E. Bosi, G. F. Bottazzo, R. Buzzetti, D. Cucinotta, A. Galluzzo, A. Falorni, and F. Dotta Identification of Tyrosine Phosphatase 2(256-760) Construct as a New, Sensitive Marker for the Detection of Islet Autoimmunity in Type 2 Diabetic Patients: The Non-Insulin Requiring Autoimmune Diabetes (NIRAD) Study 2 Diabetes, May 1, 2008; 57(5): 1276 - 1283. [Abstract] [Full Text] [PDF]

				A. Petrone, C. Suraci, M. Capizzi, A. Giaccari, E. Bosi, C. Tiberti, E. Cossu, P. Pozzilli, A. Falorni, R. Buzzetti, et al. The Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Is Associated With High GAD Antibody Titer in Latent Autoimmune Diabetes in Adults: Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study 3 Diabetes Care, March 1, 2008; 31(3): 534 - 538. [Abstract] [Full Text] [PDF]

				S. Brophy, K. Yderstraede, D. Mauricio, S. Hunter, M. Hawa, P. Pozzilli, G. Schernthaner, N. Schoot, R. Buzzetti, H. Davies, et al. Time to Insulin Initiation Cannot Be Used in Defining Latent Autoimmune Diabetes in Adults Diabetes Care, March 1, 2008; 31(3): 439 - 441. [Abstract] [Full Text] [PDF]

				T. Kobayashi, S. Tanaka, A. Shimada, and T. Maruyama High Titer of Autoantibodies to GAD Identifies a Specific Phenotype of Adult-Onset Autoimmune Diabetes: Response to Buzzetti et al. Diabetes Care, November 1, 2007; 30(11): e126 - e126. [Full Text] [PDF]

				R. Buzzetti, A. Petrone, M. Capizzi, E. Bosi, and for the Non Insulin Requiring Autoimmune Diabetes High Titer of Autoantibodies to GAD Identifies a Specific Phenotype of Adult-Onset Autoimmune Diabetes: Response to Kobayashi et al. Diabetes Care, November 1, 2007; 30(11): e127 - e127. [Full Text] [PDF]