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

126 Citations (Scopus)

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

Fingerprint

Type 1 Diabetes Mellitus
Autoantibodies
Phenotype
Antibodies
Iodide Peroxidase
Insulin
HLA-DRB1 Chains
Uric Acid
Autoimmunity
Type 2 Diabetes Mellitus
Fasting
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Buzzetti, R., Di Pietro, S., Giaccari, A., Petrone, A., Locatelli, M., Suraci, C., ... 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

High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. / Buzzetti, Raffaella; Di Pietro, Sergio; Giaccari, Andrea; Petrone, Antonio; Locatelli, Mattia; Suraci, Concetta; Capizzi, Marco; Arpi, Maria Luisa; Bazzigaluppi, Elena; Dotta, Francesco; Bosi, Emanuele.

In: Diabetes Care, Vol. 30, No. 4, 04.2007, p. 932-938.

Research output: Contribution to journalArticle

Buzzetti, R, Di Pietro, S, Giaccari, A, Petrone, A, Locatelli, M, Suraci, C, Capizzi, M, Arpi, ML, Bazzigaluppi, E, Dotta, F & Bosi, E 2007, 'High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes', Diabetes Care, vol. 30, no. 4, pp. 932-938. https://doi.org/10.2337/dc06-1696
Buzzetti R, Di Pietro S, Giaccari A, Petrone A, Locatelli M, Suraci C et al. High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. Diabetes Care. 2007 Apr;30(4):932-938. https://doi.org/10.2337/dc06-1696
Buzzetti, Raffaella ; Di Pietro, Sergio ; Giaccari, Andrea ; Petrone, Antonio ; Locatelli, Mattia ; Suraci, Concetta ; Capizzi, Marco ; Arpi, Maria Luisa ; Bazzigaluppi, Elena ; Dotta, Francesco ; Bosi, Emanuele. / High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. In: Diabetes Care. 2007 ; Vol. 30, No. 4. pp. 932-938.
@article{3f1eba1f998a4eaeb8a0df26eef44f2d,
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). 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.",
author = "Raffaella Buzzetti and {Di Pietro}, Sergio and Andrea Giaccari and Antonio Petrone and Mattia Locatelli and Concetta Suraci and Marco Capizzi and Arpi, {Maria Luisa} and Elena Bazzigaluppi and Francesco Dotta and Emanuele Bosi",
year = "2007",
month = "4",
doi = "10.2337/dc06-1696",
language = "English",
volume = "30",
pages = "932--938",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "4",

}

TY - JOUR

T1 - High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes

AU - Buzzetti, Raffaella

AU - Di Pietro, Sergio

AU - Giaccari, Andrea

AU - Petrone, Antonio

AU - Locatelli, Mattia

AU - Suraci, Concetta

AU - Capizzi, Marco

AU - Arpi, Maria Luisa

AU - Bazzigaluppi, Elena

AU - Dotta, Francesco

AU - Bosi, Emanuele

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34147140060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147140060&partnerID=8YFLogxK

U2 - 10.2337/dc06-1696

DO - 10.2337/dc06-1696

M3 - Article

C2 - 17392553

AN - SCOPUS:34147140060

VL - 30

SP - 932

EP - 938

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 4

ER -