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Diabetologia. 2013 Jul;56(7):1615-22. doi: 10.1007/s00125-013-2896-y. Epub 2013 Mar 29.

Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet autoantibody-positive children.

Author information

1
Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany. peter.achenbach@helmholtz-muenchen.de

Abstract

AIMS/HYPOTHESIS:

Islet autoantibody-positive children progress to type 1 diabetes at variable rates. In our study, we asked whether characteristic autoantibody and/or gene profiles could be defined for phenotypes showing extreme progression.

METHODS:

Autoantibodies to insulin (IAA), GAD (GADA), insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) were measured in follow-up sera, and genotyping for type 1 diabetes susceptibility genes (HLA-DR/HLA-DQ, INS variable number of tandem repeats [VNTR] and single nucleotide polymorphisms at PTPN22, PTPN2, ERBB3, IL2, SH2B3, CTLA4, IFIH1, KIAA0350 [also known as CLEC16A], CD25, IL18RAP, IL10, COBL) was performed on the DNA samples of children born to a parent with type 1 diabetes and prospectively followed from birth for up to 22 years.

RESULTS:

Of the 1,650 children followed, 23 developed multiple autoantibodies and progressed to diabetes within 3 years (rapid progressors), while 24 children developed multiple autoantibodies and remained non-diabetic for more than 10 years from seroconversion (slow progressors). Rapid and slow progressors were similar with respect to HLA-DR/HLA-DQ genotypes, development of IAA, GADA and ZnT8A, and progression to multiple autoantibodies. In contrast, IA-2A development was considerably delayed in the slow progressors. Furthermore, both groups were effectively distinguished by the combined presence or absence of type 1 diabetes susceptibility alleles of non-HLA genes, most notably IL2, CD25, INS VNTR, IL18RAP, IL10, IFIH1 and PTPN22, and discrimination was improved among children carrying high-risk HLA-DR/HLA-DQ genotypes.

CONCLUSIONS/INTERPRETATION:

Our data suggest that genotypes of non-HLA type 1 diabetes susceptibility genes influence the likelihood or rate of diabetes progression among children with multiple islet autoantibodies.

PMID:
23539116
DOI:
10.1007/s00125-013-2896-y
[Indexed for MEDLINE]

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