痛性糖尿病神经病变的诊断与治疗

痛性糖尿病神经病变(PDN)是糖尿病的常见并发症之一,以自发痛、痛觉过敏和触诱发痛为特征,严重影响糖尿病患者的生活质量.目前PDN的诊断主要基于对临床表现、辅助检查,以及一系列诊断、筛查PDN的评分量表的综合分析.PDN的治疗涉及多个层面,以症状控制为主.基于治疗PDN的药物疗效不佳且有不良反应的影响,目前PDN的治疗效果仍不乐观.早发现、早诊断、早治疗是提高患者生活质量的关键,在临床上有重要意义.     

Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy

Aims/hypothesis The largely unsatisfactory results reported for the pharmacological treatment of diabetic neuropathy has spurred the search for alternative therapies. The aim of this study was to evaluate the efficacy of frequency-modulated electromagnetic neural stimulation (FREMS) as a novel treatment for painful diabetic neuropathy.Methods Patients (n=31) with painful neuropathy associated with decreased nerve conduction velocity (<40 m/s) and increased vibration perception threshold (>25 V) were enrolled in a randomised, double-blind, crossover study designed to compare the effects of FREMS with those of placebo. Each patient received two series of ten treatments of either FREMS or placebo in random sequence, with each series lasting no more than 3 weeks. The primary efficacy end point was the change in pain measured by a visual analogue scale (VAS).Results FREMS induced a significant reduction in daytime and night-time VAS pain score (all p<0.02). Furthermore, FREMS induced a significant increase in sensory tactile perception, as assessed by monofilament; a decrease in foot vibration perception threshold, as measured by a biothesiometer; and an increase in motor nerve conduction velocity (all p<0.01). No significant changes were observed after placebo. Comparison of measurements at the 4-month follow-up with those at baseline revealed that a significant benefit persisted for all measures that showed an improvement at the end of treatment, with an additional improvement in quality of life evaluated by the Short Form-36 questionnaire (all p<0.05). No significant side effects were recorded during the study.Conclusions/interpretation FREMS is a safe and effective therapy for neuropathic pain in patients with diabetes and is able to modify some parameters of peripheral nerve function.     

Prevalence and risk factors for diabetic peripheral neuropathy,neuropathic pain and foot ulceration in the Arabian Gulf region

Aims/IntroductionThis study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN), painful DPN and diabetic foot ulceration (DFU) in patients with type 2 diabetes in secondary healthcare in Qatar, Kuwait and the Kingdom of Saudi Arabia.Materials and MethodsAdults aged 18–85 years with type 2 diabetes were randomly enrolled from secondary healthcare, and underwent clinical and metabolic assessment. DPN was evaluated using vibration perception threshold and neuropathic symptoms and painful Diabetic Peripheral Neuropathy was evaluated using the Douleur Neuropathique 4 questionnaire.ResultsA total of 3,021 individuals were recruited between June 2017 and May 2019. The prevalence of DPN was 33.3%, of whom 52.2% were at risk of DFU and 53.6% were undiagnosed. The prevalence of painful DPN was 43.3%, of whom 54.3% were undiagnosed. DFU was present in 2.9%. The adjusted odds ratios for DPN and painful DPN were higher with increasing diabetes duration, obesity, poor glycemic control and hyperlipidemia, and lower with greater physical activity. The adjusted odds ratio for DFU was higher with the presence of DPN, severe loss of vibration perception, hypertension and vitamin D deficiency.ConclusionsThis is the largest study to date from the Middle East showing a high prevalence of undiagnosed DPN, painful DPN and those at risk of DFU in patients with type 2 diabetes, and identifies their respective risk factors.     

血压控制不佳是痛性糖尿病周围神经病变的危险因素:前瞻性队列研究

目的通过前瞻性研究设计明确血压控制不佳是否为痛性糖尿病周围神经病变(DPN)发病的危险因素。方法本研究为前瞻性研究。自2014年起从上海5家社区卫生中心纳入年龄≥18岁未诊断DPN的患者。记录所有患者在基线纳入和随访结束时的基本资料、实验室检查和密西根神经病变筛查量表检查结果,并在随访结束时接受神经病理性疼痛问卷评估和神经传导功能检查。根据痛性DPN标准,将患者分为非DPN组、痛性DPN组和无痛性DPN组。比较非DPN组、痛性DPN组和无痛性DPN组患者基线及随访时临床资料,分析痛性DPN组和无痛性DPN组患者基线(收缩压、舒张压)、随访(收缩压、舒张压)以及随访和基线时血压差值的差异,并采用χ²检验比较血压控制不佳组(≥130/80 mmHg,1 mmHg=0.133 kPa)和血压控制良好组(<130/80 mmHg)痛性DPN发生率的差异,采用多因素logistic回归模型进一步分析血压控制不佳与痛性DPN之间的关系。结果最终纳入315例T2DM患者,随访(5.06±1.14)年,将患者分为非DPN组152例、痛性DPN组74例和无痛性DPN组89例。与非DPN组患者相比,痛性DPN组和无痛性DPN组患者基线的年龄、腰围和空腹血糖明显升高,差异有统计学意义(P<0.05);痛性DPN组患者基线时的糖尿病病程、收缩压和舒张压明显高于非DPN组患者(P<0.05)。痛性DPN组患者随访时的收缩压(P=0.030)和舒张压(P=0.007)明显高于无痛性DPN组,差异有统计学意义(P<0.05)。基线血压控制不佳组患者132例,血压控制良好组患者30例,基线血压控制不佳组痛性DPN的发生率49.24%(65/132)高于基线血压控制良好组26.67%(8/30),差异有统计学意义(P=0.025)。校正体重指数、糖化血红蛋白、年龄、性别、吸烟、饮酒、T2DM病程、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、服用血管紧张素转化酶抑制剂、其他降压药及二甲双胍后,血压控制不佳仍然与痛性DPN相关(OR=17.921,95%CI为1.497~214.593)。结论血压控制不佳为T2DM患者痛性DPN的危险因素。     

去甲肾上腺素及其受体在痛性糖尿病神经病变中的作用

去甲肾上腺素(NE)作为中枢神经系统和交感神经系统中广泛分布的一种单胺类神经递质,其在疼痛方面的调节作用不容忽视.NE及其受体系统与痛性糖尿病神经病变的发生密切相关,外周NE递质受体系统主要起促痛作用,中枢NE递质受体系统则主要起镇痛作用,有关NE及其受体系统的研究对痛性糖尿病神经病变的防治有重要意义.     

Prevalence and clinical implications of painful diabetic peripheral neuropathy in type 2 diabetes: Results from a nationwide hospital-based study of diabetic neuropathy in Korea

Aims

To determine the prevalence and risk factors for painful diabetic peripheral neuropathy (PDPN) and evaluate sleep impairment and quality of life in patients with PDPN.

Methods

Data from the Korean Diabetes Association Neuropathy Study Group were used to evaluate 3999 patients with type 2 diabetes. PDPN was diagnosed using visual analogue scales (VAS) and medical history. The patients were asked to answer the Brief Pain Inventory-Short Form (BPI-SF), Medical Outcomes Study Sleep (MOS-Sleep) Scale, EuroQol (EQ-5D), and VAS.

Results

Among the patients with diabetic peripheral neuropathy (n = 1338), 577 (43.1%) were diagnosed with PDPN (14.4% of all patients with type 2 diabetes). PDPN was independently associated with age, female gender, fasting plasma glucose, hypertension, and previous cerebrovascular events. All pain severity and interference measures were higher in patients with PDPN than in non-PDPN patients, and patients with PDPN reported more impaired sleep and lower EQ-5D and VAS scores.

Conclusions

The prevalence of PDPN in Koreans was comparable to that in Western populations. PDPN may impair sleep and quality of life compared with non-PDPN, and physicians should carefully consider pain symptoms in patients with diabetic peripheral neuropathy.     

Blood flow patterns in painful diabetic neuropathy

Summary Peripheral blood flow is known to be qualitatively increased in diabetic patients with neuropathy. We have measured the actual blood flow in the feet of diabetic patients with neuropathy using non-invasive mercury strain gauge plethysmography and Doppler sonogram techniques and shown that it is increased on average five times above normal at an ambient temperature of 20 °–22 °C. Moreover, reduction of this high flow by sympathetic arousal stimuli proved possible in those with severe painful neuropathy contrasting strongly with failure to reverse it in those with severe non-painful sensory neuropathy. Reduction of blood flow was associated with reduction in neuropathic pain. We studied 22 diabetic patients with severe sensory neuropathy and eight with painful neuropathy. High resting foot blood flows were demonstrated in both groups with neuropathy. The big toe flow in those with severe sensory neuropathy was 29.3±9.2 ml · min^–1 · 100 ml^–1 (mean±SD) and in the painful neuropathy group, 25.9±7.5, compared with 5.2±2.4ml · min^–1 · 100ml^–1 in the non-diabetic control subjects (p<0.001). High foot skin temperatures were also recorded in the groups with neuropathy, reflecting the high blood flow. The subjects with painful neuropathy retained the ability to constrict peripheral blood vessels in response to arousal stimuli, and reduce peripheral flow on average by 32% compared with the patients with sensory neuropathy who responded on average by only 10%. The demonstration of a peripheral sympathetic defect, responsible for the high blood flow and the potential reversal of such flow in painful neuropathy may be important in our further understanding of the aetiology of such pain and its treatment.     

痛性糖尿病周围神经病变的临床治疗进展

痛性糖尿病周围神经病变(PDPN)是一种常见的较难治疗的糖尿病并发症,疼痛症状常导致患者抑郁和生活质量下降.治疗主要是针对潜在疾病,要控制好血糖,防止神经病变进展.缓解疼痛是治疗糖尿病周围神经病变(DPN)的重点与难点.目前疗法主要包括药物和物理治疗.药物主要有抗氧化剂、神经营养因子、抗抑郁药、抗癫痫药、抗心律失常药、麻醉类镇痛药及中药等.新一代药物不良反应较少,为治疗PDPN提供了新的选择.本文就其治疗的进展及机制作一综述.     

糖尿病痛性周围神经病的临床及电生理特点分析

目的探讨糖尿病痛性周围神经病（PDPN）的临床和电生理特点。方法严格入选32例PDPN患者,病程〉1年,疼痛视觉模拟评分〉4,未伴有其他内科系统合并症,进行视觉模拟评分（VAS）并记录疼痛性质。电生理检测包括：常规神经传导速度（NCV）、定量感觉检测（温度觉）（QST-t）。结果PDPN往往有客观的感觉异常,但神经系统体征不典型,NCV检测可正常,而QST—t可有异常表现,本组NCV检测13例正常,其中11例QST-t异常;本组NCV异常率为59．4％,QST异常率为87．5％,QST＋NCV异常率为93．7％。VAS与QST的上下肢热痛觉（HP）呈正相关（t=0．595、P=0．009;t=0．784、P=0．004）,与胫神经的感觉神经传导速度（SCV）呈负相关（t=-0．554;P=0．032）;与其它电生理各项参数不相关,与空腹血糖、糖化血红蛋白、病程及疼痛病程不相关。结论PDPN以小纤维受累为主,QST可为早期PDPN提供客观的临床依据;疼痛程度与C类纤维及下肢胫神经感觉纤维病变有一定的相关性。     

硫辛酸联合普瑞巴林治疗痛性糖尿病神经病变的临床疗效观察

目的探讨硫辛酸联合普瑞巴林治疗痛性糖尿病神经病变的临床疗效。方法将84例痛性糖尿病神经病变患者随机分为对照组和观察组各42例,对照组给予硫辛酸治疗,观察组给予硫辛酸联合普瑞巴林治疗,均治疗4周,观察两组患者治疗前后疼痛程度、神经传导速度变化及不良反应发生情况。结果观察组患者治疗后疼痛视觉模拟评分(VAS)降低幅度明显优于对照组(P0.01)。两组患者治疗后神经传导速度均较前增快,组间比较差异无统计学意义(P0.05)。观察组显效5例,有效35例,无效2例。对照组显效3例,有效31例,无效8例。观察组疗效优于对照组(Z=1.88,P0.05),但两组不良反应发生率比较差异无统计学意义(P0.05),均无严重不良反应发生。结论硫辛酸联合普瑞巴林治疗痛性糖尿病神经病变能更好地缓解疼痛,提高治疗效果,临床应用安全有效。     

Glycaemic control for painful diabetic peripheral neuropathy is more than fasting plasma glucose and glycated haemoglobin

BackgroundThe relationship between postprandial hyperglycaemia and diabetic peripheral neuropathy (DPN), whether painful or painless, has yet to be determined. Thus, the aim of this study was to investigate the relationship in patients with type 2 diabetes (T2D).MethodsThis cross-sectional study was conducted in adults with T2D between January and October 2013. Blood samples were collected after overnight fasting every 3 months prior to enrolment. For this study, increased postprandial glycaemic exposure was defined as high glycated haemoglobin (HbA_1c) and near-normal mean fasting plasma glucose (FPG) levels. Both painless and painful DPN were evaluated using two validated tools, the Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique 4 (DN4) questionnaire.ResultsThis study included 1040 participants with mean FPG levels < 140 mg/dL, 535 of which were < 126 mg/dL. Of these patients, 200/1040 (19.2%) and 105/535 (19.6%) had DPN. Multivariate analysis demonstrated that higher HbA_1c levels (≥ 7%) did not increase risk of painless DPN, but did significantly increase risk of painful DPN in T2D patients with FPG < 140 mg/dL and < 126 mg/dL, with corresponding odds ratios of 2.49 and 3.77 (95% confidence intervals: 1.09–5.71 and 1.20–11.79), respectively, after adjusting for demographic factors, diabetes-related variables and comorbidities.ConclusionThis study is the first to reveal that increased postprandial glycaemic exposure, as assessed by high HbA1c and near-normal FPG levels, is associated with an increased risk of painful DPN in adults with T2D.     

Variability of fasting plasma glucose and the risk of painful diabetic peripheral neuropathy in patients with type 2 diabetes

Aim

The relationship between glycaemic variability and painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetes (T2D) is unclear. The aim of this study was to investigate whether variations in fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), were associated with the risk of PDPN in patients with T2D.

Heart rate‐corrected QT interval: A novel diagnostic biomarker for diabetic peripheral neuropathy

Aims/IntroductionTo explore the relationship between heart rate‐corrected QT (QTc) interval and diabetic peripheral neuropathy (DPN), and whether QTc interval has diagnostic utility for DPN beyond nerve conduction velocity.Materials and MethodsA total of 965 patients with diabetes, including 473 patients with DPN and 492 patients without DPN, underwent standard 12‐lead electrocardiography and detailed assessments of peripheral neuropathy.ResultsPatients with DPN had longer QTc intervals than those without. Among participants, from the first to fourth quartile of QTc interval, the proportion of patients with DPN appreciably increased and the nerve conduction velocity obviously decreased (P for trend <0.001). The univariate and multivariate analyses showed that prolonged QTc interval was closely associated with increased risk of DPN (univariable odds ratio 1.112, 95% confidence interval 1.097–1.127, P < 0.001; multivariable odds ratio 1.118, 95% confidence interval 1.099–1.137, P < 0.001). Receiver operating characteristic analysis for the diagnosis of DPN showed a greater area under the curve for QTc interval of 0.894 than the median nerve motor conduction velocity of 0.691, median nerve sensory conduction velocity of 0.664 and peroneal nerve motor conduction velocity of 0.692. The optimal cut‐off point of QTc interval for DPN was 428.5 ms with sensitivity of 0.715 and specificity of 0.920 (P < 0.001). The combination of QTc interval and nerve conduction testing increased the area under the curve for the diagnosis of DPN (from 0.736 to 0.916; P < 0.001).ConclusionsQTc interval with 428.5 ms has more reliable diagnostic utility for DPN than nerve conduction velocity, and prolonged QTc interval is closely associated with an increased risk of DPN.     

Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus

Aims

To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese.

综合分析法诊断糖尿病周围神经病变对其临床特点和发病危险因素的影响

目的:通过临床和仪器等检查,综合分析诊断糖尿病周围神经病变,探讨其临床特点与发病相关危险因素的变化。方法:筛选434例2型糖尿病患者,收集其一般临床数据,如病史、身高、体重、血压、空腹血糖(FPG)、餐后2h血糖(PPG)、空腹血浆胰岛素(FIns)水平和血脂指标等,结合神经传导速度(NCV)、定量感觉检查(QST)(包括温度觉、振动觉、触觉和痛觉)结果,将其分为有或非糖尿病神经病变组,统计分析神经病变发病情况以及与这些指标的关系。结果:入选糖尿病患者的NCV检查异常率为52.3%,QST异常为62.9%,综合分析结果异常为63.6%,随着年龄和糖尿病病程的增长,神经病变的发生率增加;神经病变组的年龄、糖尿病病程、糖尿病家族史、吸烟史、饮酒史、身高、体重指数、收缩压、PPG、FIns水平、尿微量蛋白、血肌酐(Scr)等数据明显高于非神经病变组,并与神经病变发病相关(P<0.05),这些指标中年龄、身高、糖尿病病程、PPG、FIns水平、Scr是神经病变发病的危险因素(P<0.05)。结论:结合临床和仪器检查综合分析诊断糖尿病神经病变符合疾病的实际特点,最大限度地减少漏诊;分析后的发病相关危险因素与其他诊断方法相似。     

加巴喷丁治疗糖尿病性神经痛的研究进展

糖尿病性神经痛是神经病理性疼痛的一个主要类型,患病人数多,治疗困难.加巴喷丁是一种新型的抗癫痫药物,目前被广泛应用十治疗糖尿病性神经痛,其镇痛机制尚未完全明确,对电压门控钙通道α2δ-1亚单位的调节作用可能是其主要作用机制.加巴喷丁治疗糖尿病神经性疼痛效果明确,不良反应轻微,是治疗糖尿病性神经痛较为理想的药物.     

糖尿病周围神经病变的诊断方法

糖尿病周围神经病变( DPN)难以治愈,不仅影响患者生活质量,还易造成其足部疼痛、溃疡、截肢等不良后果.现有的DPN诊断方法或对早期病变灵敏度低,如临床评分方法、单丝检测;或为侵入性检查,如皮肤活检、神经活检,亟需灵敏、简单、有效且安全的方法.一些新的诊断技术如泌汗功能检测、足底压力测定、角膜共聚焦显微镜等也已在临床上开始应用.