Autoantibodies (A) against Neuropeptide Y (NPY), was reported in 9% newly diagnosed type 1 diabetes (T1D) patients. A single nucleotide polymorphism (SNP) at rs16139 (T1128C) within the NPY‐gene identified an amino acid substitution from leucine (L) to proline (P) (L7P) associated with both glucose tolerance and type 2 diabetes. We aimed to determine: (i) the influence of autoantibodies to leucine neuropeptide Y (NPY‐LA) and autoantibodies to proline neuropeptide Y (NPY‐PA) on the diagnostic sensitivity of type 1 diabetes (T1D), (ii) the association of NPYA with major islet autoantibodies, and (iii) the association of NPYA with HLA‐DQ genotypes in newly diagnosed T1D patients.

Serum from the HLA‐DQ typed T1D patients (n = 673; median age 10 yr) from Skåne, Sweden, were analyzed for autoantibodies against NPY‐L and NPY‐P in a radioligand binding assay, and against glutamic acid decarboxylase 65 (GAD65), insulin, insulinoma associated protein‐2 (IA‐2), and zinc transporter 8 (ZnT8) in addition to islet cell antibodies (ICA). A total of 1006 subjects (median age 9 yr) were used as controls.

A total of 9.2% (n = 62) of the T1D patients were positive for NPY‐LA (p < 0.001) and 7.6% (n = 51) for NPY‐PA (p < 0.001) compared to 1.1% (n = 11) in controls. The NPY‐LA and NPY‐PA appeared together (κ = 0.63; p < 0.001) and the median levels correlated (R² = 0.603; p < 0.001). T1D patients diagnosed after 10 yr of age were at an increased risk for NPYA at diagnosis [odds ratio (OR = 2.46; 95% CI 1.46–4.16; p = 0.001)] adjusted for age at diagnosis, gender, autoantibody positivity, and HLA.

NPY is a minor autoantigen in children with newly diagnosed T1D. Therefore, NPY autoantibodies may be investigated in T1D autoimmunity.