Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: Non Insulin Requiring Autoimmune Diabetes (NIRAD) 4.
OBJECTIVE
Zinc transporter 8 (ZnT8) is an islet beta-cell secretory granule membrane protein recently identified as an autoantibody antigen in type 1 diabetes. The aim of this study was to determine the prevalence and role of antibodies to ZnT8 (ZnT8As) in adult-onset diabetes.


METHODS
ZnT8As were measured by a radioimmunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH(2)-terminal proteins in 193 patients with adult-onset autoimmune diabetes having antibodies to either GAD (GADAs) or IA-2 (IA-2As) and in 1,056 antibody-negative patients with type 2 diabetes from the Non Insulin Requiring Autoimmune Diabetes (NIRAD) study.


RESULTS
ZnT8As-COOH were detected in 18.6% patients with autoimmune diabetes and 1.4% with type 2 diabetes. ZnT8As-NH(2) were rare. ZnT8As were associated with younger age and a high GADA titer. The use of GADAs, IA-2As, and ZnT8As in combination allowed a stratification of clinical phenotype, with younger age of onset of diabetes and characteristics of more severe insulin deficiency (higher fasting glucose and A1C, lower BMI, total cholesterol, and triglycerides) in patients with all three markers, with progressive attenuation in patients with two, one, and no antibodies (all P(trend) < 0.001). Autoantibody titers, association with high-risk HLA genotypes, and prevalence of thyroid peroxidase antibodies followed the same trend (all P < 0.001).


CONCLUSIONS
ZnT8As are detectable in a proportion of patients with adult-onset autoimmune diabetes and seem to be a valuable marker to differentiate clinical phenotypes.
Lampasona
Vito
V
Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy.
Petrone
Antonio
A
Tiberti
Claudio
C
Capizzi
Marco
M
Spoletini
Marialuisa
M
di Pietro
Sergio
S
Songini
Marco
M
Bonicchio
Sara
S
Giorgino
Francesco
F
Bonifacio
Ezio
E
Bosi
Emanuele
E
Buzzetti
Raffaella
R
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015531:Radioimmunoprecipitation Assay; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D027682:Cation Transport Proteins; C096322:ICA512 autoantibody; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8