Abnormalities of foot pressure in early diabetic neuropathy

Dynamic foot pressure has been studied in 44 diabetic subjects of mean age 52 years with no clinical evidence of neuropathy and in an age and sex matched non-diabetic control group. Vibration perception threshold (VPT), sensory (SCV), and motor conduction velocities (MCV) were also measured in the diabetic subjects. Sixteen diabetic subjects (Group A) had abnormally high pressures under the metatarsal heads (greater than 10 kg/cm2), whereas the remaining 28 diabetic subjects had normal results (Group B). The ratio of toe to metatarsal head loading (normal 0.112) was significantly reduced in Group A (0.077) compared to Group B (0.127: p less than 0.05). VPT and sural nerve SCV were also significantly abnormal in Group A subjects compared with Group B (p less than 0.005 and p less than 0.02, respectively), though there were no differences in MCV. A significant inverse correlation was obtained between toe loading and VPT. It is concluded that abnormalities of foot pressure occur in early sensory neuropathy and may precede clinical abnormalities. Assessment of the toe-loading ratio may provide a sensitive measure of motor dysfunction in early diabetic neuropathy.     

Hidden dangers revealed by misdiagnosed diabetic neuropathy: A comparison of simple clinical tests for the screening of vibration perception threshold at primary care level

Aim

Diabetic peripheral neuropathy is an important complication and contributes to the morbidity of diabetes mellitus. Evidence indicates early detection of diabetic peripheral neuropathy results in fewer foot ulcers and amputations. The aim of this study was to compare different screening modalities in the detection of diabetic peripheral neuropathy in a primary care setting.

The potential of transdermal nitric oxide treatment for diabetic peripheral neuropathy and diabetic foot ulcers

The Center for Disease Control (CDC) estimates that 29 million Americans have diabetes, and 70% of diabetic patients develop diabetic peripheral neuropathy [1,2]. Up to 27% of the direct medical cost of diabetes may be attributed to DPN [3]. A 2013 article from the American Diabetes Association reported a $176 billion direct medical cost of diabetes in 2012 [4]. DPN patients often suffer from shooting and burning pain in their distal limbs and a severe loss of sensation. Diabetic foot ulcers, infections, and amputations may follow. Currently available treatments: tricyclic antidepressants, anticonvulsants such as gabapentin and pregabalin, serotonin and norepinephrine reuptake inhibitor, duloxetine, topical 5% lidocaine (applied to the most painful area) can manage painful symptoms but do not address the underlying pathologies of DPN and diabetic wound ulcers. A combination of pain-reducing medications can provide relief when individual medications fail, and opioids such as tramadol and oxycodone may be administered with these medications to reduce pain [5]. Due to the prevalence of diabetes, DPN, and diabetic foot ulcers, and because of the lack of available effective treatments to directly address the pathology contributing to these conditions, novel treatments are being sought. Our hypothesis is that a deficiency of nitric oxide synthase in diabetic patients leads to a lack of vascularization of the peripheral nerves, which causes DPN; and this could be treated with vasodilators such as nitric oxide. In this paper, the mechanisms of DPN are reviewed and analyzed to elucidate the potential of a transdermal nitric oxide application for the treatment of DPN and diabetic wound ulcers by increasing vasodilation.     

2型糖尿病患者听觉阈值与周围神经病变的关系分析

目的 通过比较无糖尿病的人群和2型糖尿病患者的纯音听阈值、振动觉阈值(VPT),了解2型糖尿病患者周围神经病变(DPN)与耳聋的关系.方法 测定173例研究对象的VPT及纯音听阈值,2型糖尿病患者同时测定感觉神经传导速度(SCV)和运动神经传导速度(MCV),将其分为对照组35例,无糖尿病神经病变组74例,糖尿病伴神经病变组64例.比较3组的基本情况、感音神经性耳聋(SNHL)发生率、纯音听阈值和VPT值,分析听阈值和神经传导速度的关系.结果 伴神经病变的糖尿病组SNHL发生率为29.69%,明显高于无糖尿病神经病变组(17.57%)和对照组(17.14%),且3组的年龄、糖尿病病程、HbA1c、糖化血清蛋白(GA)、空腹血糖、餐后2 h血糖、VPT和听阈值之间有显著性差异(均P＜0.05).不同VPT亚组的听阈值之间也存在明显差异(均P＜0.05).正中神经传导速度与1.00、2.00、4.00、8.00kHz听阈值呈明显负相关,logistic回归分析显示,年龄(回归系数=0.088,P＜0.01)是SNHL的独立危险因素,正中神经MCV(回归系数=-0.135,P=0.046)是影响SNHL的重要因素.结论 糖尿病患者易影响中高频听力,DPN患者常同时合并听力受损,年龄、正中神经MCV是影响SNHL的主要危险因素.

Abstract：

Objective In order to investigate the relationship between hearing loss and diabetic peripheral neuropathy( DPN ) via comparing the pure tone thresholds and vibration perception threshold(VPT) in type 2 diabetic patients and control person without diabetes. Methods 173 subjects including 138 type 2 diabetic patients(DM)and 35 non-diabetes controls were examined for VPT and hearing threshold. Nerve conducting velocity ( NCV )including sensory nerve conducting velocity( SCV )and motorial nerve conducting velocity( MCV )of diabetic patients were determined. The participants were divided into three groups: control group (n = 35 ), DM group without peripheral neuropathy( non-PN group, n = 74 ), and DM group complicated with peripheral neuropathy (PN group,n = 64 ). The clinical characteristics, biochemical parameters , the incidence of sensorineural hearing loss ( SNHL),pure tone threshold, and VPT were compared among three groups. At last, the relationship between hearing thresholds and NCV were analyzed. Results The incidence of hearing impairment of sensorineural type was 29.69% in PN group, which was significantly higher than that of non-PN group( 17.57% )and control group( 17. 14% ). There was significant differences in age, duration of diabetes, glycolated hemoglobin (HbA1c), glycolated serum albumin ( GA), Fasting blood glucose( FPG), 2h postprandial blood glucose( PPG), VPT, and hearing threshold among the three groups( all P＜0. 05 ). The value of hearing threshold increased significantly( all P＜0. 05 ) in 3 VPT subgroups with VPT≤ 15 V, VPT 16-25 V, and VPT ＞25 V. The Spearman correlation analysis showed median NCV was negatively correlated with hearing threshold on 1.00, 2.00, 4. 00, and 8. 00 kHz ( All P ＜ 0. 05 ). The logistic regression analysis indicated that the age( regression coefficient =0. 088, P＜0. 01 ) was the independent risk factor of SNHL, median nerve MCV ( regression coefficient = -0. 135, P = 0. 046 ) was the important influencing factor of SNHL. Conclusion Diabetic patients are more likely to suffer from impaired middle-frequency and high-frequency hearing, DPN in patients is often complicated with hearing impairment. Age and median nerve MCV were major risk factors of SNHL in diabetic patients.     

欧米诺汗印法对糖尿病周围神经病变的早期诊断意义初探

目的评估泌汗神经功能检测在诊断2型糖尿病(T2DM)患者早期周围神经病变中的价值。方法分别采用DNS评分法和欧米诺汗印法(新型诊断膏贴,Neuropad)对218例T2DM患者进行外周神经病变评估及泌汗神经功能检测,计算欧米诺汗印法、10g单纤丝、振动觉、温度觉及针刺痛觉的单项检查相对于DNS评分法对周围神经病变诊断的灵敏度和特异度。结果糖尿病周围神经病变组欧米诺汗印法变色时间为19·1±8·1min,显著高于糖尿病无神经病变组的8·3±1·8min和对照组的3·9±0·8min(P<0·01);欧米诺汗印法测得的周围神经病变发病率为61·9%略高于DNS测得的57·8%。相对于DNS评分法,欧米诺汗印法诊断周围神经病变的敏感度为92·8%,特异度为82·2%阳性预告值82·6%;单项的10g单纤丝、振动觉、足背部温度觉及痛觉测试的灵敏度分别为69·0%、33·3%、67·4%和57·1%,特异度分别为81·5%、90·2%、80·4%和84·8%。欧米诺汗印法变色时间与DNS评分呈显著正相关(r=0·46,P<0·01),优于其他4种单项检查。结论欧米诺汗印法是一种简易、有重要参考价值的检测方法,其对糖尿病患者足部泌汗功能的检测有助于糖尿病周围神经病变的早期筛查。     

维生素D缺乏与糖尿病周围神经病变

糖尿病周围神经病变（DPN）患者中普遍存在维生素D缺乏的现象.1,25（OH）2D3作为维生素D的活性形式,通过与细胞内的维生素D受体（VDR）结合发挥生物学作用.已有研究证明DPN与维生素D缺乏之间具有相关性.维生素D缺乏导致DPN的机制尚不完全清楚,但有资料证实维生素D缺乏可导致神经系统发育障碍、神经损伤及神经变性性疾病,减弱抗炎作用,促进动脉粥样硬化发展,损害胰岛β细胞功能及上调基质金属蛋白酶水平,进一步导致DPN的发生和发展.     

震动感觉阈值检查在糖尿病神经病变诊断中的应用

震动感觉阈值检查（VPT）用于诊断糖尿病神经病变简便、无创、重复性好、患者顺应性好。其敏感性优于其他依赖临床症状、体征的方法和尼龙单丝检查。本文介绍VPT及其与其他临床常用诊断糖尿病神经病变方法的比较，简述了VPT检查时需要注意的问题，如年龄、探头的压力、检查者的经验和患者对于检查的理解等。     

The Neuropad test: a visual indicator test for human diabetic neuropathy

Aims/hypothesis The commercially available Neuropad test was developed as a simple visual indicator test to evaluate diabetic neuropathy. It uses a colour change to define the integrity of skin sympathetic cholinergic innervation. We compared the results of Neuropad assessment in the foot with established measures of somatic and autonomic neuropathy. Methods Fifty-seven diabetic patients underwent Neuropad assessment, quantitative sensory and autonomic function testing, and evaluation of intra-epidermal nerve fibre density in foot skin biopsies. Results Neuropad responses correlated with the neuropathy disability score (r _s = 0.450, p < 0.001), neuropathic symptom score (r _s = 0.288, p = 0.03), cold detection threshold (r _s = 0.394, p = 0.003), heat-as-pain perception threshold visual analogue score 0.5 (r _s = 0.279, p = 0.043) and deep-breathing heart rate variability (r _s = −0.525, p < 0.001). Intra-epidermal nerve fibre density (fibres/mm) compared with age- and sex-matched control subjects (11.06 ± 0.82) was non-significantly reduced (7.37 ± 0.93) in diabetic patients with a normal Neuropad response and significantly reduced in patients with a patchy (5.01 ± 0.93) or absent (5.02 ± 0.77) response (p = 0.02). The sensitivity of an abnormal Neuropad response in detecting clinical neuropathy (neuropathy disability score ≥5) was 85% (negative predictive value 71%) and the specificity was 45% (positive predictive value 69%). Conclusions/interpretation The Neuropad test may be a simple indicator for screening patients with diabetic neuropathy.     

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.     

2型糖尿病患者振动觉阈值检测及影响因素

目的 探讨振动觉阈值检测对2型糖尿病患者下肢神经病变的诊断意义及其影响因素.方法 测定2008年8月至2009年4月在我院内分泌代谢科门诊就诊的1018例2型糖尿病患者振动觉阈值,根据振动觉阈值风险度将其分为低风险组(<15 V)484例、中风险组(15～25 V)302例、高风险组(>25 V)232例.比较患者下肢神经病变症状、基本情况和血糖控制指标,分析其影响因素.采用卡方检验、t检验、单因素方差分析等进行统计学分析.结果 低风险组、中风险组、高风险组分别占47.54%、29.67%、22.79%,中风险组、高风险组有神经病变症状者所占比例明显高于低风险组(分别为61.26%、65.52%、39.26%).各组年龄、糖尿病病程、收缩压、糖化血红蛋白及糖化血清蛋白差异有统计学意义(均P<0.05),男性振动觉阈值明显高于女性(P<0.01).振动觉阈值与年龄、性别、糖尿病病程、收缩压、糖化血红蛋白、糖化血清蛋白、空腹血糖呈正相关(P<0.05).多元回归分析显示年龄(P=0.000)、糖化血红蛋白(P=0.046)及糖化血清蛋白(P=0.030)是振动觉阈值的独立影响因素.结论 采用振动觉阈值检测筛查门诊2型糖尿病患者糖尿病周围神经病变的患病率为22.79%,年龄、糖化血红蛋白、糖化血清蛋白是振动觉阈值的独立影响因素.     

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.     

糖尿病周围神经病变检查方法的研究现状

糖尿病周围神经病变是糖尿病最常见的并发症之一,目前其检查方法有很多,包括常用于判断糖尿病神经病变的严重性及监测其发展过程的诊断方法,如神经传导功能检查及定量感觉检查等.还有一些形态学及物理学检查方法,如神经活检、皮肤活检、角膜神经的共聚焦显微镜检查等.目前多用于基础实验窜研究,其临床的实用性有待进一步研究.     

Usefulness of the vibration perception thresholds measurement as a diagnostic method for diabetic peripheral neuropathy: Results from the Rio de Janeiro type 2 diabetes cohort study

Aims

To investigate the associated factors with the vibration threshold perception (VPT) in patients with type 2 diabetes and to assess whether it is useful for detection of diabetic peripheral neuropathy (DPN).

Thermoregulatory sudomotor dysfunction and diabetic neuropathy develop in parallel in at-risk feet

Aims To establish the longitudinal relationship of foot complications to neuropathy based on a 4-year follow-up of diabetic patients stratified by sudomotor dysfunctions. Methods One hundred and nineteen Type 2 diabetic patients and 36 non-diabetic subjects were initially registered in the prospective cohort study. Plantar skin temperature and sympathetic skin response (SSR) were used to monitor sympathetic mediated thermoregulation and sudomotor function. Peripheral somatic and central autonomic functions were studied using clinical, nerve conduction and cardiovascular reflex tests. At enrolment, the diabetic patients were classified into one of three groups by the progressive stages of sudomotor dysfunction: SSR+ (SSR present; 49 patients), SSR− (SSR absent; 41 patients) and at-risk group (SSR absent but with cracked skin involving partial thickness of the dermis; 29 patients). Results The at-risk group had 13.4 times (95% confidence interval 1.4–125.7) higher plantar ulceration rates than the other two patient groups during the 4 years. Skin temperature elevation occurred in parallel with development of foot sweating problems. There were no significant differences between the three patient groups in the ratios of abnormal heart rate variation, orthostatic test and clinical neuropathy score at follow-up. After 4 years of follow-up, nerve conduction abnormalities were more frequent in the at-risk and SSR− groups than in the SSR+ group. Conclusions Early deterioration of small sympathetic fibres could not be quantified accurately by the clinical, somatic and autonomic tests. Assessing skin integrity and sudomotor function in at-risk individuals identifies early peripheral sympathetic neuropathy, even if the patients have no overt clinical symptoms.     

Evaluation of thermal and vibration sensation in diabetic neuropathy

Summary Sensory evaluation of diabetic neuropathy was undertaken by a new technique for assessment of thermal sensitivity. The method is simple and reproducible, and the mean normal value of the lateral border of the foot was 6.0 °C (3.6–9.8 °C, 95% confidence limits). Four groups of patients with diabetic neuropathy were examined: 22 with neuropathic ulcers and/or Charcot joints (groups 1 and 2); all showed severe abnormalities (range 10.8->30 °C), frequently more than three times the upper limit of normal. In contrast thermal sensitivity in 15 patients with painful neuropathy (group 4) varied from normal to grossly abnormal (range 3.9->30 °C) confirming this form of neuropathy as a distinct entity. The majority of those 10 patients with autonomic neuropathy alone (group 3) had abnormal thermal sensitivity (range 6.4->30 °C). Comparison of thermal sensitivity (a small fibre modality) with vibration perception threshold (a large fibre modality) showed that thermal sensitivity is sometimes selectively affected, especially in those with painful neuropathy, suggesting that the small fibres are more vulnerable in diabetes. Frequent involvement of the hands confirms the stocking and glove distribution of diabetic neuropathy. We conclude that impairment of thermal sensivity is the rule in symptomatic diabetic neuropathy and its assessment provides a simple quantitive measurement suitable for long-term studies of its natural history.     

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.     

糖尿病周围神经病变的检查方法及其诊断效率

糖尿病周围神经病变是糖尿病最常见的并发症之一,目前糖尿病周围神经病变的检查方法有很多,包括常用于评估和量化糖尿病神经病变症状严重程度的临床评分方法,如神经病变残疾评分(NDS)、密西根神经病变筛查量表(MNSI)评分等;筛查方法如单丝检查、音叉检查等;常用于判断糖尿病神经病变的严重性及监测其发展过程的诊断方法,如神经传导功能检查及定量感觉检查等;还有一些形态学的检查,如神经活检、皮肤活检等,目前多用于基础实验室研究,其临床的实用性有待进一步研究。     

Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review

Introduction

Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients.

黄芩甙治疗糖尿病周围神经病变的初步观察

目的观察黄芩甙对醛糖还原酶（AR）活性的抑制作用及其对糖尿病神经病变的疗效。方法74例糖尿病患者随机分为黄芩甙治疗组和对照组,治疗组每天服黄芩甙3g。结果黄芩甙治疗后患者红细胞AR活性显著降低（1．29±0．64U／gHbvs2．42±0．85U／gHb,P＜0．01）;黄芩甙缓解神经病变症状总有效率为583％,明显高于对照组（3．3％,P＜0．01）;治疗后黄芩甙组神经传导速度趋于稳定,部分项目略有改善,而对照组则呈进行性恶化趋势,两组腓总神经、胫神经传导速度有显著性差异,分别为31．4±6．1m／svs269±5．3m／s（P＜0．05）和31．8±5．2m／svs26．5±4．8m／s（P＜0．05）,黄芩甙组的腓总神经、医神经末端潜伏期明显绍短,分别为5．00±0．64m／svs5．60±0．56m／s（P＜0．05）和5．10±0．58m／svs5．60±0．57m／s（P＜0．05）,正中神经和尺神经的感觉神经动作电位波幅也显著提高（P＜0．05）。未见明显不良反应及肝肾毒性。结论黄芩甙在体内具有明显的AR活性抑制作用,可有效的缓解糖尿病周围神经病变的临床症状,改善其神经传导速度,从而有助于防止糖尿病神经病变的发生与发展。