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Diabetologia. 2006 May;49(5):881-90. Epub 2006 Mar 3.

Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk.

Author information

1
Diabetes and Metabolism, Department of Clinical Science at North Bristol, University of Bristol, Southmead Hospital, UK. polly.bingley@bristol.ac.uk

Abstract

AIMS/HYPOTHESIS:

To examine the role of additional immune, genetic and metabolic risk markers in determining risk of diabetes in islet cell antibody (ICA)-positive individuals with a family history of type 1 diabetes recruited into the European Nicotinamide Diabetes Intervention Trial.

METHODS:

Five hundred and forty-nine first-degree relatives with confirmed ICA levels > or =20 Juvenile Diabetes Foundation units (mean age 15.9 years; interquartile range 10.4-33.7 years) were recruited from 20 countries. OGTTs and IVGTTs were performed at baseline, antibodies to glutamate decarboxylase (GADA), protein tyrosine phosphatase (IA-2A) and insulin (IAA) were determined by RIA, and HLA class II genotyping was performed by PCR of sequence-specific oligonucleotides.

RESULTS:

One hundred and fifty-nine participants developed diabetes within 5 years. Univariate analysis showed that the cumulative risk of development of diabetes within 5 years varied according to age, relationship to the proband, positivity for IAA, IA-2A and GADA, number and combination of islet antibodies, HLA class II genotype, baseline glucose tolerance, and first-phase insulin secretion, but not gender or incidence of childhood type 1 diabetes in the background population. Children aged < or =10 years had a 59% risk of diabetes within 5 years, compared with 11% in those > or =25 years (p<0.0001). Using multivariate analysis, independent determinants were age, first-phase insulin response, baseline glucose tolerance and number of additional antibody markers, but not antibody type or genotype. Individuals <25 years with two or more additional antibodies at baseline had a 62% risk of diabetes within 5 years and these combined criteria identified 81% of the cases in the whole cohort.

CONCLUSIONS/INTERPRETATION:

We suggest that screening and recruitment for future intervention trials should be limited to family members aged <25 years, and should be based on islet autoantibodies alone.

PMID:
16514546
DOI:
10.1007/s00125-006-0160-4
[Indexed for MEDLINE]

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