title: 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.
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.affiliation: Diabetes Research Center, Brussels Free University, Brussels, Belgium.
authors.forename: F K
authors.initials: FK
authors.lastname: Gorus
authors.forename: E V
authors.initials: EV
authors.lastname: Balti
authors.forename: I
authors.initials: I
authors.lastname: Vermeulen
authors.forename: S
authors.initials: S
authors.lastname: Demeester
authors.forename: A
authors.initials: A
authors.lastname: Van Dalem
authors.forename: O
authors.initials: O
authors.lastname: Costa
authors.forename: H
authors.initials: H
authors.lastname: Dorchy
authors.forename: S
authors.initials: S
authors.lastname: Tenoutasse
authors.forename: T
authors.initials: T
authors.lastname: Mouraux
authors.forename: C
authors.initials: C
authors.lastname: De Block
authors.forename: P
authors.initials: P
authors.lastname: Gillard
authors.forename: K
authors.initials: K
authors.lastname: Decochez
authors.forename: J M
authors.initials: JM
authors.lastname: Wenzlau
authors.forename: J C
authors.initials: JC
authors.lastname: Hutton
authors.forename: D G
authors.initials: DG
authors.lastname: Pipeleers
authors.forename: I
authors.initials: I
authors.lastname: Weets
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood* / Q000191:economics; D001530:Belgium; D001786:Blood Glucose / Q000276:immunology; D027682:Cation Transport Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D018450:Disease Progression; D005190:Family; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D008297:Male; D011236:Prediabetic State / Q000097:blood* / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology*; D012042:Registries; D012306:Risk; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D027682:Cation Transport Proteins; D007328:Insulin; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2