Xingyun Hu,1,* Jie Peng,2,* Qingxian Li,3 Yuying Chen,4 Yingjuan Zeng,5 Peishan Li,4 Chuan Yang4 

1Department of General Practice, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Endocrinology, Shenzhen Longhua District Central Hospital, Shenzhen, People’s Republic of China; 4Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Department of Endocrinology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Peishan Li; Chuan Yang, Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yanjiang West Road No. 107, Guangzhou, 510120, People’s Republic of China, Email lipsh26@mail2.sysu.edu.cn; yangch@mail.sysu.edu.cn

Purpose: The role of FAM134B in neurological diseases has received significant attention; however, its role in diabetic peripheral neuropathy (DPN) remains unexplored. This study investigated the association between plasma FAM134B levels and DPN while assessing its diagnostic value.
Methods: The study included 128 inpatients with type 2 diabetes divided into DPN (n = 68) and non-DPN (n = 60) groups. FAM134B expression was determined via qRT-PCR analysis of plasma FAM134B mRNA level. All clinical data were retrieved from the Hospital Information System. SPSS and R were used for statistical analyses.
Results: Plasma FAM134B mRNA levels were significantly higher in the DPN than in the non-DPN group (p < 0.001). Increased FAM134B mRNA levels were strongly linked to increased odds of DPN, with the highest quartile showing a significant risk elevation (Odds Ratio [OR] = 21.42, 95% Confidence Interval: 4.86– 96.46, p < 0.001). Restricted cubic spline analysis confirmed a non-linear relationship, thereby identifying a critical threshold of FAM134B mRNA levels at 2.53, above which the risk sharply increased (adjusted OR = 3.11, p = 0.006). Subgroup analysis showed consistent associations across most subgroups, with a notable difference in males (p = 0.038). The diagnostic performance was moderate (Area Under the Curve [AUC] = 0.756). While adding FAM134B mRNA to the model did not dramatically improve the AUC, it significantly enhanced reclassification metrics (Net Reclassification Improvement = 0.165, Integrated Discrimination Improvement = 0.095, p < 0.05), thereby highlighting its clinical value.
Conclusion: Increased FAM134B expression positively correlated with the odds of DPN, and may act as a promising target for diagnostic and therapeutic interventions.
Plain Language Summary: Diabetic peripheral neuropathy (DPN) is a common diabetic complication without effective treatment to block or reverse its progression currently. FAM134B is thought to be closely linked with neurological disease in previous studies, potentially playing a pivotal role in DPN.Plasma FAM134B mRNA levels were significantly increased in individuals with DPN and markedly associated with increased odds of DPN. Different statistical models demonstrated that FAM134B had an excellent diagnostic predictive value for DPN.Our findings provide a theoretical foundation for the development of FAM134B as a potential target for diagnostic and therapeutic interventions of DPN.

Keywords: FAM134B, type 2 diabetes, diabetic peripheral neuropathy, clinical value