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

I: Pediatric Diabetes, Vol. 13, Nr. 6, 2012, s. 454-462.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Andersen, MLM, Vaziri Sani, F, Delli, A, Porksen, S, Jacobssen, E, Thomsen, J, Svensson, J, Petersen, JS, Hansen, L, Lernmark, Å, Mortensen, HB & Nielsen, LB 2012, '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', Pediatric Diabetes, vol. 13, nr. 6, s. 454-462. https://doi.org/10.1111/j.1399-5448.2012.00857.x

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Andersen, Marie Louise M. ; Vaziri Sani, Fariba ; Delli, Ahmed ; Porksen, Sven ; Jacobssen, Emma ; Thomsen, Jane ; Svensson, Jannet ; Petersen, Jacob Steen ; Hansen, Lars ; Lernmark, Åke ; Mortensen, Henrik B. ; Nielsen, Lotte B. / 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. I: Pediatric Diabetes. 2012 ; Vol. 13, Nr. 6. s. 454-462.

RIS

TY - JOUR

T1 - 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

AU - Andersen, Marie Louise M.

AU - Vaziri Sani, Fariba

AU - Delli, Ahmed

AU - Porksen, Sven

AU - Jacobssen, Emma

AU - Thomsen, Jane

AU - Svensson, Jannet

AU - Petersen, Jacob Steen

AU - Hansen, Lars

AU - Lernmark, Åke

AU - Mortensen, Henrik B.

AU - Nielsen, Lotte B.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - residual beta-cell function

KW - stimulated C-peptide

KW - SLC30A8

KW - type 1

KW - diabetes

KW - ZnT8 autoantibodies

U2 - 10.1111/j.1399-5448.2012.00857.x

DO - 10.1111/j.1399-5448.2012.00857.x

M3 - Article

VL - 13

SP - 454

EP - 462

JO - Pediatric Diabetes

T2 - Pediatric Diabetes

JF - Pediatric Diabetes

SN - 1399-543X

IS - 6

ER -