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Autoantibodies to insulin, insulinoma-associated antigen-2, and zinc transporter 8 improve the prediction of early insulin requirement in adult-onset autoimmune diabetes


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Title: Autoantibodies to insulin, insulinoma-associated antigen-2, and zinc transporter 8 improve the prediction of early insulin requirement in adult-onset autoimmune diabetes
Authors: Kawasaki, Eiji / Nakamura, Kan / Kuriya, Genpei / Satoh, Tsuyoshi / Kuwahara, Hironaga / Kobayashi, Masakazu / Abiru, Norio / Yamasaki, Hironori / Eguchi, Katsumi
Issue Date: Feb-2010
Publisher: The Endocrine Society
Citation: Journal of Clinical Endocrinology & Metabolism, 95(2), pp.707-713; 2010
Abstract: Objective: The aim of this study was to indentify the predictive marker for early insulin requirement in adult-onset autoimmune diabetes in the Japanese populations.Design/Patients: We analyzed insulin autoantibodies (IAA), IA-2 autoantibodies (IA-2icA), and ZnT8 autoantibodies (ZnT8A) by radioimmunoassay in 47 Japanese patients with adult-onset autoimmune diabetes who were identified by native GAD autoantibody (nGADA) screening in ~3,000 non-insulin-requiring diabetes and in 302 nGADA-negative type 2 diabetes. Furthermore, GAD65 autoantibody-specific epitopes were also analyzed using GAD65/GAD67 chimeric constructs.Results: The prevalence of IAA, IA-2icA and ZnT8A in nGADA-positive patients was 26%, 15%, and 19%, respectively, which was significantly higher than that in nGADA-negative type 2 diabetes (2%, 2%, and 2%, P<0.0001). Among nGADA-positive patients, 38% had one or more of IAA, IA-2icA, or ZnT8A, and 15% had two or more of these autoantibodies, compared with none of the nGADA-negative patients (P<0.0001). Thirty-six % of nGADA-positive patients subsequently required insulin therapy, and high nGADA titer (log-rank P=0.003), middle epitope recognition of GAD65A (P=0.002), and the presence of one or more of IAA, IA-2icA, or ZnT8A (P=0.002) at diagnosis marked the risk for early requirement of insulin therapy. Multivariate logistic regression analysis showed the multiple islet autoantibodeis to be independently associated with the risk for insulin requirement (Odds ratio=13.77, 95%CI: 2.77-68.45, P=0.001).Conclusions: These results indicate that the determination of IAA, IA-2icA, and ZnT8A improves the prediction of a future insulin insufficiency in adult-onset autoimmune diabetes, which appears to be superior to GADA titer and GAD65A-specific epitopes.
Keywords: Autoantibodies / Epitope / Insulin / Japanese population / Prediction / Type 1 diabetes / Zinc transporter-8
URI: http://hdl.handle.net/10069/24667
ISSN: 0021972X / 19457197
DOI: 10.1210/jc.2009-1733
Rights: Copyright © 2010 by The Endocrine Society
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/24667

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