High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes.
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.
Buzzetti
Raffaella
R
Department of Clinical Sciences, La Sapienza University, Rome, Italy. raffaella.buzzetti@uniroma1.it
Di Pietro
Sergio
S
Giaccari
Andrea
A
Petrone
Antonio
A
Locatelli
Mattia
M
Suraci
Concetta
C
Capizzi
Marco
M
Arpi
Maria Luisa
ML
Bazzigaluppi
Elena
E
Dotta
Francesco
F
Bosi
Emanuele
E
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
D001323:Autoantibodies; D007328:Insulin; D005968:Glutamate Decarboxylase