2 research outputs found
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.
RESEARCH DESIGN AND 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