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Title
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IA-2 autoantibodies predict impending type I diabetes in siblings of patients
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Author
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Institution/Organisation
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Belgian Diabetes Registry
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Abstract
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| Aims/hypothesis. Multiple islet autoantibody positivity is currently believed to best predict progression to Type I (insulin-dependent) diabetes mellitus. We compared its predictive value with that of positivity for a particular type of islet autoantibody, directed against the IA-2 antigen. Methods. Autoantibodies against islet cell cytoplasm (ICA), insulin (IAA), GAD (GADA) and IA-2 (IA-2A) were measured at initial sampling in 1724 non-diabetic siblings (median age [range]: 16 [0-39] years) of Type I diabetic patients with a median follow-up of 50 months. Results. On initial sampling 11% of siblings were positive for one antibody type or more and 2.1% for three of more types. During follow-up, 27 antibody-positive siblings developed diabetes. Using survival analysis, the risk for clinical onset within 5 years was 34% in subjects positive for three or more types compared with 13% in those with one type or more. Progression to diabetes amounted to 12% within 5 years among siblings positive for IAA, 20% for ICA, 19% for GADA but 59% for IA-2A (p<0.001 vs absence of the respective antibody). IA-2A were detected in 1.7% of all siblings and in 56% of the prediabetic subjects on first sampling. Initial positivity for two or three antibody markers was associated with a higher progression rate in IA-2A positive as compared to IA-2A negative siblings (p=0.001). In absence of IA-2A initial positivity for another antibody (IAA, ICA or GADA) conferred a low (<10% within 5 years) risk of diabetes compared to subjects lacking this antibody. Conclusions/interpretation. In siblings of Type I diabetic patients, IA-2A positivity is a more direct predictor of impending clinical onset than multiple antibody positivity per se. Assessment of IA-2A status allows us to select subjects with homogeneously high risk of diabetes for participation in prevention trials. |
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Language
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English
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Source (journal)
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Diabetologia / European Association for the Study of Diabetes. - Berlin, 1965, currens
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Publication
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Berlin
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2002
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ISSN
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0012-186X
[print]
1432-0428
[online]
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DOI
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10.1007/S00125-002-0949-8
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Volume/pages
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45
:12
(2002)
, p. 1658-1666
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ISI
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000180041600006
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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