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 Frølund Thomsen; Jannet Svensson; Jacob Steen Petersen; Lars Hansen; Ake Lernmark; Henrik B Mortensen; Lotte B Nielsen

doi: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

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

19 Citations (Scopus)

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 language	English
Journal	Pediatric Diabetes
Volume	13
Issue number	6
Pages (from-to)	454-62
Number of pages	9
ISSN	1399-543X
DOIs	https://doi.org/10.1111/j.1399-5448.2012.00857.x
Publication status	Published - Sept 2012

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Andersen, M. L. M., Vaziri-Sani, F., Delli, A., Pörksen, S., Jacobssen, E., Thomsen, J. F., Svensson, J., Steen Petersen, J., Hansen, L., Lernmark, A., Mortensen, H. B., & Nielsen, L. B. (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, 13(6), 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 et al.

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

Research output: Contribution to journal › Journal article › Research › peer-review

Andersen, MLM, Vaziri-Sani, F, Delli, A, Pörksen, S, Jacobssen, E, Thomsen, JF, Svensson, J, Steen Petersen, J, Hansen, L, Lernmark, A, 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

@article{3c0f5d5d446b4942a2e6dbb2fe7e4ab8,

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.",

author = "Andersen, {Marie Louise M} and Fariba Vaziri-Sani and Ahmed Delli and Sven P{\"o}rksen and Emma Jacobssen and Thomsen, {Jane Fr{\o}lund} and Jannet Svensson and {Steen Petersen}, Jacob and Lars Hansen and Ake Lernmark and Mortensen, {Henrik B} and Nielsen, {Lotte B}",

note = "{\textcopyright} 2012 John Wiley & Sons A/S.",

year = "2012",

month = sep,

doi = "10.1111/j.1399-5448.2012.00857.x",

language = "English",

volume = "13",

pages = "454--62",

journal = "Pediatric Diabetes",

issn = "1399-543X",

publisher = "Wiley-Blackwell",

number = "6",

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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 Frølund

AU - Svensson, Jannet

AU - Steen Petersen, Jacob

AU - Hansen, Lars

AU - Lernmark, Ake

AU - Mortensen, Henrik B

AU - Nielsen, Lotte B

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.

U2 - 10.1111/j.1399-5448.2012.00857.x

DO - 10.1111/j.1399-5448.2012.00857.x

M3 - Journal article

C2 - 22686132

SN - 1399-543X

VL - 13

SP - 454

EP - 462

JO - Pediatric Diabetes

JF - Pediatric Diabetes

IS - 6

ER -

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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