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 ( ZnT 8) was recently identified as a common autoantigen in type 1 diabetes ( T 1 D ) and inclusion of ZnT 8 autoantibodies ( ZnT 8 A b) was found to increase the diagnostic specificity of T 1 D . Objectives The main aims were to determine whether ZnT 8 A b vary during follow‐up 1 year after diagnosis, and to relate the reactivity of three types of ZnT 8 A b to the residual stimulated C‐peptide levels during the first year after diagnosis. Subjects A total of 129 newly diagnosed T 1 D patients <15 years was followed prospectively 1, 3, 6, and 12 months after diagnosis. Methods Hemoglobin A1c, meal‐stimulated C ‐peptide, ZnT 8 A b, and other pancreatic autoantibodies were measured at each visit. Patients were genotyped for the rs13266634 variant at the SLC 30 A 8 gene and HLA ‐ DQ alleles. Results The levels of all ZnT 8 A b [ ZnT 8 A rg (arginine), ZnT 8 T rp (tryptophan), ZnT 8 G ln (glutamine)] tended to decrease during disease progression. A twofold higher level of ZnT 8 A rg and ZnT 8 G ln 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 SLC 30 A 8 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 A rg variant of the ZnT 8 autoantibodies are associated with higher levels of stimulated C ‐peptide after diagnosis of T 1 D and during follow‐up. Carriers of the TT genotype of the SLC 30 A 8 gene predict lower stimulated C ‐peptide levels 12 months after diagnosis.