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.
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.


OBJECTIVE
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.


METHODS
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 of Paediatrics, Herlev University Hospital, Herlev, Denmark. ml.max.andersen@dadlnet.dk
Marie Louise M
ML
Andersen
Fariba
F
Vaziri-Sani
Ahmed
A
Delli
Sven
S
Pörksen
Emma
E
Jacobssen
Jane
J
Thomsen
Jannet
J
Svensson
Jacob
J
Steen Petersen
Lars
L
Hansen
Ake
A
Lernmark
Henrik B
HB
Mortensen
Lotte B
LB
Nielsen
D000293:Adolescent; D000367:Age Factors; D019943:Amino Acid Substitution / Q000276:immunology / Q000502:physiology; D001120:Arginine / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics; D002096:C-Peptide / Q000097:blood*; D027682:Cation Transport Proteins / Q000235:genetics* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D050505:Mutant Proteins / Q000276:immunology; D015854:Up-Regulation; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D002096:C-Peptide; D027682:Cation Transport Proteins; D050505:Mutant Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D001120:Arginine