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

J Diabetes Complications. 2013 Nov-Dec;27(6):609-17. doi: 10.1016/j.jdiacomp.2013.06.007. Epub 2013 Jul 30.

Abstract

Aims: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: Autoimmunity; Long-term diabetes; Minor autoantigen; NPY autoantibodies; Neuropathy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Neuropathies / blood*
  • Diabetic Neuropathies / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropeptide Y / immunology*
  • Young Adult

Substances

  • Autoantibodies
  • Neuropeptide Y