Abstract |
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, Belgian Diabetes Registry |
Journal | Clinical and experimental immunology
(Clin Exp Immunol)
Vol. 171
Issue 1
Pg. 82-90
(Jan 2013)
ISSN: 1365-2249 [Electronic] England |
PMID | 23199327
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Copyright | © 2012 British Society for Immunology. |
Chemical References |
- Autoantibodies
- Blood Glucose
- Cation Transport Proteins
- Insulin
- SLC30A8 protein, human
- Zinc Transporter 8
- PTPRN protein, human
- Receptor-Like Protein Tyrosine Phosphatases, Class 8
- Glutamate Decarboxylase
- glutamate decarboxylase 2
|
Topics |
- 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
- Zinc Transporter 8
|