Abstract：
OBJECTIVE: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).
METHODS: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini-Hochberg procedure.
RESULTS: Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB-H = 0.044) and PDGFRα (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB-H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB-H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB-H>0.05).
CONCLUSIONS: This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.
METHODS: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini-Hochberg procedure.
RESULTS: Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB-H = 0.044) and PDGFRα (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB-H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB-H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB-H>0.05).
CONCLUSIONS: This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.
摘要：
目的：本研究的目的是评估神经生物标志物与远端感觉运动多神经病（DSPN）之间的关联。
方法：横断面分析基于基于人群的KORAF4调查的1032名61-82岁参与者，其中177名患者在基线时患有DSPN。2型糖尿病患病率为20%。前瞻性分析使用505名基线无DSPN参与者的数据，在KORAFF4调查之前，其中125人开发了DSPN。基于密歇根神经病变筛查仪器的检查部分定义了DSPN。使用邻近延伸测定技术测量神经生物标志物的血清水平。使用具有稳健误差方差的泊松回归来估计88个生物标志物与流行或事件DSPN之间的关联,并且表示为每1-SD增加的风险比(RR)和95%CI。使用Benjamini-Hochberg程序对多个混杂因素和多个测试的结果进行了调整。
结果：更高的CTSC血清水平（组织蛋白酶C;RR[95％CI]1.23（1.08;1.39），pB-H=0.044)和PDGFRα(血小板衍生生长因子受体A;RR[95%CI]1.21(1.08;1.35),pB-H=0.044）与总研究样本中普遍存在的DSPN相关。CDH3,JAM-B,莱恩,在糖尿病亚组中，RGMA和SCARA5与DSPN呈正相关，而GCP5在无糖尿病人群中与DSPN呈正相关（所有pB-H均为交互作用<0.05）。没有一个生物标志物显示与事件DSPN相关(所有pB-H>0.05)。
结论：这项研究确定了神经生物标志物与普遍的DSPN之间的多种新关联，这可能归因于这些蛋白质在神经炎症中的功能，神经发育和髓鞘形成。
方法：横断面分析基于基于人群的KORAF4调查的1032名61-82岁参与者，其中177名患者在基线时患有DSPN。2型糖尿病患病率为20%。前瞻性分析使用505名基线无DSPN参与者的数据，在KORAFF4调查之前，其中125人开发了DSPN。基于密歇根神经病变筛查仪器的检查部分定义了DSPN。使用邻近延伸测定技术测量神经生物标志物的血清水平。使用具有稳健误差方差的泊松回归来估计88个生物标志物与流行或事件DSPN之间的关联,并且表示为每1-SD增加的风险比(RR)和95%CI。使用Benjamini-Hochberg程序对多个混杂因素和多个测试的结果进行了调整。
结果：更高的CTSC血清水平（组织蛋白酶C;RR[95％CI]1.23（1.08;1.39），pB-H=0.044)和PDGFRα(血小板衍生生长因子受体A;RR[95%CI]1.21(1.08;1.35),pB-H=0.044）与总研究样本中普遍存在的DSPN相关。CDH3,JAM-B,莱恩,在糖尿病亚组中，RGMA和SCARA5与DSPN呈正相关，而GCP5在无糖尿病人群中与DSPN呈正相关（所有pB-H均为交互作用<0.05）。没有一个生物标志物显示与事件DSPN相关(所有pB-H>0.05)。
结论：这项研究确定了神经生物标志物与普遍的DSPN之间的多种新关联，这可能归因于这些蛋白质在神经炎症中的功能，神经发育和髓鞘形成。
