Impact of age and antibody type on progression from single to multiple autoantibodies in type 1 diabetes relatives.

Impact of age and antibody type on progression from single to multiple autoantibodies in type 1 diabetes relatives.

J Clin Endocrinol Metab. 2017 May 22;:

Authors: Bosi E, Boulware DC, Becker DJ, Buckner JH, Geyer S, Gottlieb PA, Henderson C, Kinderman A, Sosenko JM, Steck AK, Bingley PJ, Type 1 Diabetes TrialNet Study Group

Abstract
Context: Islet autoantibodies are markers of type 1 diabetes and an increase in number of autoantibodies detected during the preclinical phase is predictive of progression to overt disease.
Objective: To refine the impact of age in relation to islet antibody type on the progression from single to multiple autoantibodies in relatives of people with type 1 diabetes.
Research design and methods: We examined 994 relatives with normal glucose tolerance and positive for a single autoantibody, followed prospectively in the TrialNet Pathway to Prevention. Antibodies to GAD (GADA), insulin (IAA), IA-2 (IA-2A), zinc transporter 8 (ZnT8A) and ICA were tested every 6-12 months. The primary outcome was confirmed development of multiple autoantibodies. Age was categorized as <8yr; 8-11yr; 12-17yr; ≥18yr and optimal age breakpoints identified by recursive partitioning analysis.
Results: After median follow-up of 2 years, 141 relatives had developed ≥ 1 additional autoantibodies. Five-year risk was inversely related to age, but the pattern differed by antibody type: relatives with GADA showed a gradual decrease in risk over the four age groups, while relatives with IAA showed a sharp decrease above the age of 8 years. Recursive partitioning analysis identified age breakpoints at 14 years in relatives with GADA and at 4 years in relatives with IAA.
Conclusions: In relatives with IAA, spread of islet autoimmunity is largely limited to early childhood, while immune responses initially directed at GAD can mature over a longer period of time. These differences have important implications for monitoring these subjects and for designing prevention trials.

PMID: 28531305 [PubMed - as supplied by publisher]

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