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. 2010 Jan;33(1):104-8.
doi: 10.2337/dc08-2305. Epub 2009 Oct 6.

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

Vito Lampasona  1 , Antonio Petrone, Claudio Tiberti, Marco Capizzi, Marialuisa Spoletini, Sergio di Pietro, Marco Songini, Sara Bonicchio, Francesco Giorgino, Ezio Bonifacio, Emanuele Bosi, Raffaella Buzzetti; Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study Group
Affiliations

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

Vito Lampasona et al. Diabetes Care. 2010 Jan.

Abstract

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.

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Figures

Figure 1
Figure 1
ZnT8As directed against the COOH domain are more frequent in patients with high-titer GADA positivity. Filled symbols indicate IA-2A positivity also. Dotted line indicates the threshold for positivity.
Figure 2
Figure 2
Venn diagram of autoantibody combinations in autoantibody-positive patients with adult-onset diabetes.
See this image and copyright information in PMC

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