title: Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced β-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes.
abstract: OBJECTIVE
  This study assessed the relationship between autoantibodies against zinc transporter 8 (ZnT8A) and disease characteristics at diagnosis of type 1 diabetes and during the first 2 years.
  
  
  METHODS
  Children, younger than 15 years of age (n = 723) who were newly diagnosed with diabetes, were analyzed for ZnT8A, other diabetes-associated autoantibodies, HLA DR-DQ alleles, and metabolic status, which was monitored by pH, plasma glucose, and occurrence of ketoacidosis at diagnosis and through follow-up of C-peptide concentrations, exogenous insulin dose, and glycosylated hemoglobin for 2 years after the diagnosis.
  
  
  RESULTS
  ZnT8A positivity was detected in 530 children (73%). Positivity for ZnT8A was associated with older age (median 8.9 vs. 8.2 years, P = 0.002) and more frequent ketoacidosis (24% vs. 15%, P = 0.013). Children carrying the HLA DR3 allele were less often ZnT8A positive (66% vs. 77%, P = 0.002) than others. ZnT8A-positive children had lower serum C-peptide concentrations (P = 0.008) and higher insulin doses (P = 0.012) over time than their ZnT8A-negative peers.
  
  
  CONCLUSIONS
  Positivity for ZnT8A at diagnosis seems to reflect a more aggressive disease process before and after diagnosis.
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Matilda
authors.initials: M
authors.lastname: Juusola
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Parkkola
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Siljander
authors.affiliation: Immunogenetics Laboratory, University of Turku, Turku, Finland Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Hans K
authors.initials: HK
authors.lastname: Åkerblom
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland Folkhälsan Research Center, University of Helsinki, Helsinki, Finland Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland mikael.knip@helsinki.fi.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
mesh_terms: D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D027682:Cation Transport Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics; D005260:Female; D005387:Finland; D015803:HLA-DR3 Antigen / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000166:cytology; D008297:Male; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D027682:Cation Transport Proteins; D015803:HLA-DR3 Antigen; D007328:Insulin; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8