Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

The neurotransmitter Neuropeptide Y (NPY) was previously reported as a minor autoantigen in newly diagnosed type 1 diabetes (T1D) patients. The single nucleotide polymorphism at rs16139 (T1128C, L7P) in the NPY gene was associated with an increased risk for the development of type 2 diabetes (T2D). We aimed to develop a radiobinding assay for NPY-L (Leucine) and NPY-P (Proline) autoantibodies (A) to study the levels and the association with other islet autoantibodies and neuropathy.

Autoantibodies against NPY-L, NPY-P, ZnT8, GAD65 and IA-2 were studied in T1D (n=48) and T2D (n=26) patients with duration up to 42 and 31years. A subgroup of T1D (n=32) patients re-examined, 5-8years after first visit, was tested for peripheral (Z-score) and autonomic neuropathy (E/I ratio).

NPY-LA and NPY-PA were detected in 23% and 19% in T1D (p<0.001), and 12% and 23% in T2D patients (p<0.001) compared to 2.5% controls (n=398). The levels of NPYA declined during follow-up in the T1D patients (p<0.001). The neuropathy was not related to the NPYA or the other islet autoantibodies.

Regardless of the absence of an association between NPYA and neuropathy, NPY may contribute to the pathogenesis of T1D and T2D as a minor autoantigen.