Panou Theodoros, Gouveri Evanthia, Papazoglou Dimitrios, Papanas Nikolaos
Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Metabol Open. 2024 Nov 1;24:100328. doi: 10.1016/j.metop.2024.100328. eCollection 2024 Dec.
Diabetic neuropathy is one of the commonest complications of diabetes mellitus. Its most frequent form is diabetic peripheral neuropathy (DPN). Currently, there is no established and widely used biomarker for diagnosis and clinical staging of DPN. There is accumulating evidence that low-grade systemic inflammation is a key element in its pathogenesis. In this context, several clinical studies have so far identified potential biomarkers of DPN. These studies have enrolled both subjects with type 1 diabetes mellitus (T1DM) and subjects with type 2 diabetes mellitus (T2DM), including children with T1DM and elderly T2DM subjects. They have also evaluated participants with prediabetes. Potential biomarkers include a wide spectrum of cytokines, chemokines and immune receptors, notably interleukins (IL), mostly IL-1, IL-6 or IL-10, as well as mediators of the tumour necrosis factor-α (TNF-α) related pathway. Cell-ratios, such as neurtrophil-to-lymphocyte ratio (NLR), have yielded promising results as well. Other works have focused on adipokines and identified several signalling molecules (adiponectin, neuregulin 4, isthmin-1 and omentin) as promising biomarkers of DPN. Finally, epigenetic biomarkers have been investigated. Further experience is being gathered with the use of biomarkers in specific age groups and in the discrimination between painless and painful DPN. Prospective studies appear promising in monitoring of DPN progression, but experience is rather limited. Finally, certain cut-off values have been proposed for DPN screening, but these need confirmation. Future large-scale studies are now required to validate biomarkers and to investigate their potential clinical utility.
糖尿病神经病变是糖尿病最常见的并发症之一。其最常见的形式是糖尿病周围神经病变（DPN）。目前，尚无用于DPN诊断和临床分期的成熟且广泛应用的生物标志物。越来越多的证据表明，低度全身炎症是其发病机制的关键因素。在此背景下，多项临床研究已确定了DPN的潜在生物标志物。这些研究纳入了1型糖尿病（T1DM）患者和2型糖尿病（T2DM）患者，包括儿童T1DM患者和老年T2DM患者。他们还评估了糖尿病前期参与者。潜在生物标志物包括多种细胞因子、趋化因子和免疫受体，尤其是白细胞介素（IL），主要是IL-1、IL-6或IL-10，以及肿瘤坏死因子-α（TNF-α）相关途径的介质。细胞比率，如中性粒细胞与淋巴细胞比率（NLR），也取得了有前景的结果。其他研究则聚焦于脂肪因子，并确定了几种信号分子（脂联素、神经调节蛋白4、抑丝蛋白-1和网膜素）作为DPN的潜在生物标志物。最后，对表观遗传生物标志物进行了研究。在特定年龄组以及区分无痛性和疼痛性DPN方面使用生物标志物的经验正在不断积累。前瞻性研究在监测DPN进展方面似乎很有前景，但经验相当有限。最后，已提出了某些用于DPN筛查的临界值，但这些需要得到证实。现在需要未来的大规模研究来验证生物标志物并研究其潜在的临床应用价值。
