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

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

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalPediatric Diabetes
Volume13
Issue number6
Pages (from-to)454-62
ISSN1399-543X
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

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zinc-binding protein
Glutamine
Tryptophan
Meals
Alleles

Keywords

  • Adolescent
  • Age Factors
  • Amino Acid Substitution
  • Arginine
  • Autoantibodies
  • C-Peptide
  • Cation Transport Proteins
  • Child
  • Child, Preschool
  • Denmark
  • Diabetes Mellitus, Type 1
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Infant
  • Male
  • Mutant Proteins
  • Up-Regulation

Cite this

Andersen, Marie Louise M ; Vaziri-Sani, Fariba ; Delli, Ahmed ; Pörksen, Sven ; Jacobssen, Emma ; Thomsen, Jane ; Svensson, Jannet ; Steen Petersen, Jacob ; 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. In: Pediatric Diabetes. 2012 ; Vol. 13, No. 6. pp. 454-62.
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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 = "Adolescent, Age Factors, Amino Acid Substitution, Arginine, Autoantibodies, C-Peptide, Cation Transport Proteins, Child, Child, Preschool, Denmark, Diabetes Mellitus, Type 1, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Infant, Male, Mutant Proteins, Up-Regulation",
author = "Andersen, {Marie Louise M} and Fariba Vaziri-Sani and Ahmed Delli and Sven P{\"o}rksen and Emma Jacobssen and Jane Thomsen and Jannet Svensson and {Steen Petersen}, Jacob and Lars Hansen and {\AA}ke Lernmark and Mortensen, {Henrik B} and Nielsen, {Lotte B}",
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language = "English",
volume = "13",
pages = "454--62",
journal = "Pediatric Diabetes",
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Andersen, MLM, Vaziri-Sani, F, Delli, A, Pörksen, S, Jacobssen, E, Thomsen, J, Svensson, J, Steen Petersen, J, 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, no. 6, pp. 454-62. https://doi.org/10.1111/j.1399-5448.2012.00857.x

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; Pörksen, Sven; Jacobssen, Emma; Thomsen, Jane; Svensson, Jannet; Steen Petersen, Jacob; Hansen, Lars; Lernmark, Åke; Mortensen, Henrik B; Nielsen, Lotte B.

In: Pediatric Diabetes, Vol. 13, No. 6, 09.2012, p. 454-62.

Research output: Contribution to journalJournal articleResearchpeer-review

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 - Pörksen, Sven

AU - Jacobssen, Emma

AU - Thomsen, Jane

AU - Svensson, Jannet

AU - Steen Petersen, Jacob

AU - Hansen, Lars

AU - Lernmark, Åke

AU - Mortensen, Henrik B

AU - Nielsen, Lotte B

N1 - © 2012 John Wiley & Sons A/S.

PY - 2012/9

Y1 - 2012/9

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 - Adolescent

KW - Age Factors

KW - Amino Acid Substitution

KW - Arginine

KW - Autoantibodies

KW - C-Peptide

KW - Cation Transport Proteins

KW - Child

KW - Child, Preschool

KW - Denmark

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Infant

KW - Male

KW - Mutant Proteins

KW - Up-Regulation

U2 - 10.1111/j.1399-5448.2012.00857.x

DO - 10.1111/j.1399-5448.2012.00857.x

M3 - Journal article

VL - 13

SP - 454

EP - 462

JO - Pediatric Diabetes

JF - Pediatric Diabetes

SN - 1399-543X

IS - 6

ER -