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J Clin Endocrinol Metab. 2017 Aug 1;102(8):2881-2886. doi: 10.1210/jc.2017-00569.

Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives.

Author information

1
Diabetes Research Institute, San Raffaele Hospital and San Raffaele Vita Salute University, Milan 20132, Italy.
2
Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida 33620.
3
Department of Pediatric Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania 15224.
4
Translational Immunology Program, Benaroya Research Institute, Seattle, Washington 98101.
5
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado 80045.
6
Division of Endocrinology, University of Miami, Miami, Florida 33136.
7
School of Clinical Sciences, University of Bristol, Bristol BS2 8DZ, United Kingdom.

Abstract

Context:

Islet autoantibodies are markers of type 1 diabetes, and an increase in number of autoantibodies detected during the preclinical phase predicts progression to overt disease.

Objective:

To refine the effect of age in relation to islet antibody type on 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 who were positive for a single autoantibody, followed prospectively in the TrialNet Pathway to Prevention. Antibodies to glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated antigen 2, and zinc transporter 8 and islet cell antibodies were tested every 6 to 12 months. The primary outcome was confirmed development of multiple autoantibodies. Age was categorized as <8 years, 8 to 11 years, 12 to 17 years, and ≥18 years, and optimal age breakpoints were identified by recursive partitioning analysis.

Results:

After median follow-up of 2 years, 141 relatives had developed at least one 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, whereas relatives with IAA showed a sharp decrease above age 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, whereas immune responses initially directed at glutamic acid decarboxylase can mature over a longer period. These differences have important implications for monitoring these patients and for designing prevention trials.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00097292.

PMID:
28531305
PMCID:
PMC5546870
DOI:
10.1210/jc.2017-00569
[Indexed for MEDLINE]
Free PMC Article

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