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

Diabetes Care. 2016 Jan;39(1):118-21. doi: 10.2337/dc15-1027. Epub 2015 Oct 30.

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.

Research design and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Autoantibodies / blood*
  • C-Peptide / blood
  • Cation Transport Proteins / immunology*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / genetics
  • Female
  • Finland
  • HLA-DR3 Antigen / genetics
  • Humans
  • Insulin / therapeutic use
  • Insulin-Secreting Cells / cytology
  • Male
  • Zinc Transporter 8

Substances

  • Autoantibodies
  • C-Peptide
  • Cation Transport Proteins
  • HLA-DR3 Antigen
  • Insulin
  • SLC30A8 protein, human
  • Zinc Transporter 8