title: Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies.
abstract: OBJECTIVE
  We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A).
  
  
  METHODS
  For this analysis, 2,256 relatives positive for at least one BAA, of whom 142 developed diabetes, were tested for ZnT8A, ICA, and HLA genotype followed by biannual oral glucose tolerance tests. ZnT8A were also tested in 911 randomly chosen antibody-negative relatives.
  
  
  RESULTS
  ZnT8A were associated with the other BAA (548 of 2,256 [24.3%] BAA(+) vs. 8 of 911 [0.8%] BAA(-), P < 0.001) and BAA number (177 of 1,683 [10.5%] single-, 221 of 384 [57.6%] double-, and 150 of 189 [79.4%] triple-BAA positivity, P < 0.001). The 4-year diabetes risk was higher in single BAA(+) relatives with ZnT8A than ZnT8A(-) relatives (31 vs. 7%, P < 0.001). In multivariable analysis, age ≤ 20 years (hazard ratio 2.13, P = 0.03), IA-2A (2.15, P = 0.005), IAA (1.73, P = 0.01), ICA (2.37, P = 0.002), and ZnT8A (1.87, P = 0.03) independently predicted diabetes, whereas HLA type (high and moderate vs. low risk) and GAD65A did not (P = 0.81 and 0.86, respectively).
  
  
  CONCLUSIONS
  In relatives with one standard BAA, ZnT8A identified a subset at higher diabetes risk. ZnT8A predicted diabetes independently of ICA, the standard BAA, age, and HLA type. ZnT8A should be included in type 1 diabetes prediction and prevention studies.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, Colorado, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: David C
authors.initials: DC
authors.lastname: Boulware
authors.forename: Craig A
authors.initials: CA
authors.lastname: Beam
authors.forename: John C
authors.initials: JC
authors.lastname: Hutton
authors.forename: Janet M
authors.initials: JM
authors.lastname: Wenzlau
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Bingley
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.forename: Jay M
authors.initials: JM
authors.lastname: Sosenko
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Mahon
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D027682:Cation Transport Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D005190:Family; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8