Yagihashi Soroku
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Brain Nerve. 2011 Jun;63(6):571-82.
With the drastic increase in the number of patients with diabetes, management of neuropathy has become a critical concern because of its intractability and the socio-economic burden it poses. Epidemiological studies have shown that the levels of blood glucose and glycated hemoglobin, the duration of diabetes, and hypertension are important risk factors for the development of neuropathy. Although guidelines for the diagnosis and clinical staging of diabetic neuropathy have been proposed, only nerve conduction studies can provide a reliable diagnosis of the condition. Currently, evaluation of small fiber abnormalities has been given great emphasis, because they often appear early in the course of diabetic neuropathy. Quantitative analysis of epidermal innervation is globally performed for determining the indices of small fiber neuropathy, and recently, laser microscopic evaluation of corneal innervation was proposed as a surrogate technique for skin or nerve biopsy, to serve as a quantitative marker for neuropathy. The advantages of the latter technique are that it is non-invasive and allows for repeated observations. However, the validity of this new method requires further confirmation. Investigations on the pathogenesis of diabetic neuropathy are also increasing and diversifying, and new theories are emerging. The polyol pathway, glycation, and proinflammatory reactions are implicated in peripheral nerve injuries. Further, downstream signaling represented by alterations in protein kinase C, poly (ADP-ribose) polymerase, mitogen-activated protein kinases, and mobilization of transcription factors are likely to result in the neuropathic phenotype. Studies are underway to investigate a novel mechanism of diabetic neuropathy, with a view to developing a highly effective treatment that will restore nerve function and structure.
随着糖尿病患者数量的急剧增加，神经病变的管理已成为一个关键问题，因为其难治性以及所带来的社会经济负担。流行病学研究表明，血糖和糖化血红蛋白水平、糖尿病病程以及高血压是神经病变发生的重要危险因素。尽管已经提出了糖尿病神经病变的诊断和临床分期指南，但只有神经传导研究才能对该病症提供可靠的诊断。目前，对小纤维异常的评估受到了高度重视，因为它们常在糖尿病神经病变过程中早期出现。全球范围内都在进行表皮神经支配的定量分析以确定小纤维神经病变的指标，最近，有人提出角膜神经支配的激光显微镜评估可作为皮肤或神经活检的替代技术，作为神经病变的定量标志物。后一种技术的优点是它是非侵入性的，并且可以进行重复观察。然而，这种新方法的有效性需要进一步证实。关于糖尿病神经病变发病机制的研究也在增加且日益多样化，新理论不断涌现。多元醇途径、糖基化和促炎反应与周围神经损伤有关。此外，以蛋白激酶C、聚（ADP - 核糖）聚合酶、丝裂原活化蛋白激酶的改变以及转录因子的动员为代表的下游信号传导可能导致神经病变表型。目前正在进行研究以探究糖尿病神经病变的新机制，以期开发出一种能够恢复神经功能和结构的高效治疗方法。
