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Åke Lernmark

Principal investigator

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Association between autoantibodies to the Arginine variant of the Zinc transporter 8 (ZnT8) and stimulated C-peptide levels in Danish children and adolescents with newly diagnosed type 1 diabetes

Author

  • Marie Louise M. Andersen
  • Fariba Vaziri Sani
  • Ahmed Delli
  • Sven Porksen
  • Emma Jacobssen
  • Jane Thomsen
  • Jannet Svensson
  • Jacob Steen Petersen
  • Lars Hansen
  • Åke Lernmark
  • Henrik B. Mortensen
  • Lotte B. Nielsen

Summary, in English

Background The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D. Objectives The main aims were to determine whether ZnT8Ab vary during follow-up 1 year after diagnosis, and to relate the reactivity of three types of ZnT8Ab to the residual stimulated C-peptide levels during the first year after diagnosis. Subjects A total of 129 newly diagnosed T1D patients <15 years was followed prospectively 1, 3, 6, and 12 months after diagnosis. Methods Hemoglobin A1c, meal-stimulated C-peptide, ZnT8Ab, and other pancreatic autoantibodies were measured at each visit. Patients were genotyped for the rs13266634 variant at the SLC30A8 gene and HLA-DQ alleles. Results The levels of all ZnT8Ab [ZnT8Arg (arginine), ZnT8Trp (tryptophan), ZnT8Gln (glutamine)] tended to decrease during disease progression. A twofold higher level of ZnT8Arg and ZnT8Gln was associated with 4.6%/5.2% (p = 0.02), 5.3%/8.2% (p = 0.02) and 8.9%/9.7% (p = 0.004) higher concentrations of stimulated C-peptide 3, 6, and 12 months after diagnosis. The TT genotype carriers of the SLC30A8 gene had 45.8% (p = 0.01) and 60.1% (p = 0.002) lower stimulated C-peptide 6 and 12 months after diagnosis compared to the CC and the CT genotype carriers in a recessive model. Conclusions The levels of the Arg variant of the ZnT8 autoantibodies are associated with higher levels of stimulated C-peptide after diagnosis of T1D and during follow-up. Carriers of the TT genotype of the SLC30A8 gene predict lower stimulated C-peptide levels 12 months after diagnosis.

Department/s

  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2012

Language

English

Pages

454-462

Publication/Series

Pediatric Diabetes

Volume

13

Issue

6

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Endocrinology and Diabetes

Keywords

  • residual beta-cell function
  • stimulated C-peptide
  • SLC30A8
  • type 1
  • diabetes
  • ZnT8 autoantibodies

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1399-543X