Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
Danish Pain Research Center, Aarhus University, Aarhus, Denmark.
Brain. 2021 Jul 28;144(6):1632-1645. doi: 10.1093/brain/awab079.
Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in 30-40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycaemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc., which lead to the best therapeutic outcomes.
周围神经病变是 1 型和 2 型糖尿病最常见的并发症之一。多达一半的糖尿病患者在疾病过程中会出现神经病变，其中 30-40%的病例伴有神经性疼痛。糖尿病引起的周围神经损伤可表现为进行性远端对称性多发性神经病、自主神经病、神经根神经病和单神经病。最常见的糖尿病性神经病是远端对称性多发性神经病，我们将其简称为 DN，其特征是远端感觉或运动功能丧失呈手套和袜子样分布。DN 或其疼痛性对应物，即疼痛性 DN，与死亡率和发病率增加有关；因此，早期识别和预防措施至关重要。然而，诊断 DN 或疼痛性 DN 并不容易，特别是在早期和轻度神经病变的患者中，目前还没有单一的既定诊断金标准。在研究中，最常见的诊断方法是一个分层系统，该系统结合了症状、体征和一系列确认性测试。长期前瞻性研究的普遍缺乏限制了新形态计量学和神经生理学技术的敏感性和特异性的评估。因此，在研究和临床实践中筛查 DN 和疼痛性 DN 的最佳范例仍然不确定。在此，我们从临床和研究角度审查诊断挑战及其对管理 DN 患者的影响。除了改善血糖控制外，目前还没有针对 DN 的既定治疗方法，而对于疼痛性 DN ，仅可进行对症治疗。目前，只有不到三分之一的疼痛性 DN 患者通过现有药物治疗获得足够的疼痛缓解。DN 和疼痛性 DN 患者更精确和独特的感觉特征可能有助于确定对一种治疗方法有反应的患者与另一种治疗方法有反应的患者。详细的感觉特征将通过匹配到新的或已建立的 DN 发病机制，为有疼痛性 DN 的患者亚组提供量身定制的治疗，并改善临床试验分层，从而为患者亚组提供量身定制的治疗。需要进行大型随机临床试验，以确定导致最佳治疗效果的干预措施，如药理学、物理、认知、教育等。
