PuSH - Publication Server of Helmholtz Zentrum München

Achenbach, P.* ; Bonifacio, E.* ; Williams, A.J.* ; Ziegler, A.-G.* ; Gale, E.A.* ; Bingley, P.J.*

Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives.

Diabetologia 51, 488-492 (2008)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
AIMS/HYPOTHESIS: The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2beta (IA2betaA) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. METHODS: Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2betaA. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. RESULTS: Of 212 ICA/IA2A-positive participants (median age 12.1 years; 57% male), 113 developed diabetes (5 year cumulative risk 56%), and 148 were also GADA-positive and IAA-positive (4Ab-positive). IA2betaA were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2betaA-positive 65 vs 39% in IA2betaA-negative, p=0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p=0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2betaA, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal FPIR, p<0.0001), and 95% in those with impaired glucose tolerance (IGT) (vs 66% in those with normal glucose tolerance, p<0.0001). The median time to diagnosis of 4Ab/IA2betaA-positive participants with a low FPIR was 1.5 years. Multivariate analysis confirmed IA2betaA status, antibody number, young age, FPIR and IGT as independent determinants of risk. CONCLUSIONS/INTERPRETATION: IA2betaA are associated with a very high risk of diabetes in ICA/IA2A-positive relatives. Testing for IA2A/IA2betaA compares favourably with the IVGTT in identifying a subgroup of autoantibody-positive relatives at increased risk. IA2betaA determination should be added to screening protocols of future intervention trials.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 51, Issue: 3, Pages: 488-492 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Diabetes and Obesity (IDO)
Institute of Pancreatic Islet Research (IPI)