Objective:

To identify new biomarkers of diabetic distal symmetrical polyneuropathy (DDSP) with conduction slowing.

Background:

DDSP is associated with conduction slowing more than would be expected solely from large fiber axon loss.

Design/Methods:

We collected serum samples from 10 persons- 5 healthy controls (HC) and 5 patients with DDSP with conduction slowing (DNCS). The samples were processed and labeled by TMT and then were analyzed by nano LC-MS/MS on an Orbitrap Fusion Lumos Mass Spectrometer using the MS2 method. The protein extracts were run through LC-MS/MS on Oribtrap Velos MS instrument for subsequent data analysis. The MS/MS spectra were searched against the UniProt human database using the Sequest search engine on Proteome Discoverer (V2.4) platform. The relative protein abundance was calculated based on spectrum counting.

Results:

The DDSP patients’ average Overall Neuropathy Limitations Scale (ONLS), Rasch-Built Overall Disability Scale (R-ODS), Total Neuropathy Score, and HBA1C were 2.8, 32.4, 18.8, and 7.75% respectively. A total of 1,226 protein groups were identified of which 95 proteins were found significantly changed in the ratio of DNCS/HC. The ratio of DNCS/HC protein was significantly increased in 53 proteins (ratio>1, P<0.05) and decreased in 42 proteins (ratio<1, P<0.05)

Conclusions:

Proteomics analysis is a useful, high-throughput method for screening biomarkers that indicated impairment in nerve conduction in DDSP. Future studies will include DDSP without conduction slowing, diabetic patients without neuropathy and CIDP patients. The goal is to identify specific biomarkers for early diagnosis and prognosis of DDSP including DDSP with conduction slowing consistent with demyelination