Document Detail


Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients.
MedLine Citation:
PMID:  23199327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA(+) , GADA(+) , IA-2A(+) and/or ZnT8A(+) relatives (6·1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0-9, 10-19 and 20-39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age-independent in IA-2A(+) and/or ZnT8A(+) relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10-39 years), screening for IA-2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for ≥ 2 antibodies among IAA, GADA, IA-2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA-2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost-effective to select participants for intervention trials than conventional screening.
Authors:
F K Gorus; E V Balti; I Vermeulen; S Demeester; A Van Dalem; O Costa; H Dorchy; S Tenoutasse; T Mouraux; C De Block; P Gillard; K Decochez; J M Wenzlau; J C Hutton; D G Pipeleers; I Weets;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-02-19     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  82-90     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Autoantibodies / blood*,  economics
Belgium
Blood Glucose / immunology
Cation Transport Proteins / immunology*
Child
Child, Preschool
Diabetes Mellitus, Type 1 / blood,  immunology*
Disease Progression*
Family
Female
Glutamate Decarboxylase / immunology
Humans
Insulin / immunology
Male
Prediabetic State / blood*,  immunology
Receptor-Like Protein Tyrosine Phosphatases, Class 8 / immunology*
Registries
Risk
Grant Support
ID/Acronym/Agency:
P30-DK-57516/DK/NIDDK NIH HHS; R01 DK052068/DK/NIDDK NIH HHS; R01-DK-052068/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Blood Glucose; 0/Cation Transport Proteins; 0/Insulin; 0/SLC30A8 protein, human; EC 3.1.3.48/PTPRN protein, human; EC 3.1.3.48/Receptor-Like Protein Tyrosine Phosphatases, Class 8; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 2
Comments/Corrections

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