Ke Lin,1,* Xiaocui Wang,2,* Tao Gu,3,* Keduo Feng,1 Wang Zeng,1 Liu Yang1 

1Department of Neurology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China; 2Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China; 3Department of Radiology, Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ke Lin; Liu Yang, Department of Neurology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China, Email ayalinke@126.com; 510586640@qq.com

Aim: To assess the plasma concentrations of the novel hepatokine fetuin-B in individuals with type 2 diabetes with or without diabetic peripheral neuropathy (DPN), and to evaluate the relationship among fetuin-B levels, nervous function, and metabolic parameters.
Methods: A total of 333 participants were recruited and divided into three groups: DPN, painful DPN (pDPN), and non-DPN. Metabolic parameters, peripheral neuropathy-associated indices, and general biochemical parameters were also measured.
Results: Compared with the non-DPN group, general parameters, including age, SBP, BUN, Cr, and ALT, were significantly higher in the DPN and pDPN groups, and FPG, HbA1c, TC, TG, LDL, BUN, Cr, and UA levels were higher in the pDPN group. The neuropathy symptom score (NSS), neuropathy disability score (NDS), and Douleur Neuropathique en 4 Questions (DN4) were highest in the pDPN group, followed by the DPN group, and lowest in the non-DPN group. Moreover, fetuin B levels showed the same trends as peripheral neuropathy indices. Additionally, oxidative stress markers showed a decrease in total antioxidant capacity (TAC) and an increase in malondialdehyde (MDA) across all groups, with the most pronounced changes observed in pDPN patients. Bivariate correlation analysis showed that fetuin B levels were positively correlated with FPG, TC, LDL, NSS, NDS, DN4, and MDA levels, and negatively associated with TAC after adjusting for age and sex. Furthermore, nerve conduction velocity, including MLT, MRT, SRS, and SLT, showed decreasing trends among tertiles of fetuin B levels.
Conclusion: The current study suggests that circulating fetuin-B levels may be associated with the progression of pDPN and highlights the effects of hepatokine-mediated liver-to-peripheral nervous system crosstalk in DPN.

Keywords: diabetes, diabetic peripheral neuropathy, fetuin-B, glucose, lipids