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

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@article{8bce37b36e2c4e099dd44f8cc80a4652,
title = "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",
abstract = "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.",
keywords = "residual beta-cell function, stimulated C-peptide, SLC30A8, type 1, diabetes, ZnT8 autoantibodies",
author = "Andersen, {Marie Louise M.} and {Vaziri Sani}, Fariba and Ahmed Delli and Sven Porksen and Emma Jacobssen and Jane Thomsen and Jannet Svensson and Petersen, {Jacob Steen} and Lars Hansen and {\AA}ke Lernmark and Mortensen, {Henrik B.} and Nielsen, {Lotte B.}",
year = "2012",
doi = "10.1111/j.1399-5448.2012.00857.x",
language = "English",
volume = "13",
pages = "454--462",
journal = "Pediatric Diabetes",
issn = "1399-543X",
publisher = "Wiley-Blackwell",
number = "6",

}