The relationship between neuron-specific enolase, high sensitivity C reactive protein, and diabetic peripheral neuropathy in Chinese patients with type 2 diabetes: A prospective nested case–control analysis

Abstract Background Diabetic peripheral neuropathy (DPN) involves a very complex pathogenesis, and there is no neuro-specific marker for risk prediction. Neuron-specific enolase (NSE), a key enzyme in glycolysis, has a broad spectrum neurotrophic and neuroprotective effect on neurons, and also cause injury and inflammatory response of peripheral nerves. The relationship between neuron-specific enolase, highly sensitive c-reactive protein (hsCRP), and diabetic peripheral neuropathy remains unclear. We aimed to investigate whether elevated serum NSE and hsCRP levels increased the risk of DPN in patients with type 2 diabetes. Materials and methods In this prospective nested case–control study, a total of 1072 eligible subjects with type 2 diabetes constituted the follow-up cohort. Demographic data and parameters including serum NSE and hsCRP were collected at baseline. Two neuropathy screening scales (MNSI and MDNS) were used to assess DPN during follow-up period. Nerve conduction studies were performed at the end of follow-up. Conditional logistic regression was used to inspect the risk factors of the incidence of DPN. Results During an average follow-up period of 5.1 years, 176 subjects developed DPN. Serum NSE and hsCRP levels at baseline were significantly higher in DPN group than in matched non-DPN groups ( p < 0.001). NSE was positively correlated with age and hsCRP ( p < 0.001). The amplitude of sensory nerve action potential and compound muscle action potential of the lower extremity nerves were significantly decreased in the high tertile of NSE. After adjustment for matching and confusing factor, conditional logistic regression showed the risk of DPN in the high tertile of NSE level was still 3.176 times higher than that in the low tertile of NSE level ( p < 0.001). Conclusion Elevated serum NSE levels predicted the high incidence of DPN in Chinese patients with type 2 diabetes for an average of 5.1 years, which may be associated with increased neuroinflammatory response caused by high NSE levels, but further studies are needed.