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Journal of Clinical Endocrinology & Metabolism, Vol 81, 4264-4267, Copyright © 1996 by Endocrine Society

ARTICLES

Antiislet autoantibodies usually develop sequentially rather than simultaneously

L Yu, M Rewers, R Gianani, E Kawasaki, Y Zhang, C Verge, P Chase, G Klingensmith, H Erlich, J Norris and GS Eisenbarth
Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver 80262, USA.

The goal of this study was to address whether antiislet autoantibodies appear sequentially or simultaneously before the onset of type I diabetes. We analyzed sequential serum samples from 155 siblings and offspring (aged < 7 yr) of patients with type I diabetes from the Denver Diabetes Autoimmunity Study in the Young study and from a separate group of first degree relatives (aged 2-40 yr) for autoantibodies reacting with three defined autoantigens: glutamic acid decarboxylase (GAD65), insulin, and ICA512/IA-2. The youngest age at which 1 of the 3 autoantibodies appeared was 1.1 yr, and the oldest was 60.9 yr. Of the total 26 autoantibody conversion events observed, in only 3 instances did more than 1 autoantibody appear simultaneously. Among individuals (n = 12) with sequential conversion to expression of multiple autoantibodies, anti-GAD65 autoantibodies or antiinsulin autoantibodies appeared first (4 expressed antiinsulin autoantibodies first, and 8 anti-GAD65 autoantibodies first). We conclude that antiislet autoantibodies usually appear sequentially and not simultaneously. This corroborates early suggestions that humoral autoimmunity to islets develops chronically in a process usually measured in months to years. As expression of multiple autoantibodies is associated with a high risk of progression to diabetes, and sequential appearance of autoantibodies can occur late in life, long term follow-up is necessary to fully delineate the relationship of diabetes risk to autoantibody expression.


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