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。     

C肽变化与糖尿病周围神经病变的关系

目的探讨C肽变化与糖尿病周围神经病变（DPN）的关系。方法检测120例2型糖尿病（T2DM）患者的空腹血糖、餐后2h血糖、糖化血红蛋白、空腹C肽（FC—P）、餐后2hC肽（2hC—P）、尿微量白蛋白及神经传导速度（NCN）。根据患者有无DPN分为DPN组及非DPN组,按病程分为〈5a组、5-10a组、〉10a组,比较各组C肽水平。结果DPN组2hC—P明显低于非DPN组,且不同病程组两两比较均有统计学差异（P均〈0．05）。与正常者比较,DPN组运动、感觉纤维异常者的NCV及2hC—P均明显降低（P〈0．05或〈0．01）。结论2hC—P水平与T2DM患者的DPN密切相关。     

Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine (Tegretol®): Double blind crossover trial

Summary A double blind crossover study with placebo and carbamazepine was done in 30 diabetic patients who presented diverse clinical types of peripheral diabetic neuropathy. The active drug offered symptomatic relief of all sensory manifestations in 28 cases. No effort was made to assess the action of carbamazepine upon motor or visceral manifestations of neuropathy. There were two complete failures. Untoward effects were frequent but usually mild and transient; two patients presented a rash that required discontinuation of the drug.

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Symptomatische Behandlung der peripheren diabetischen Neuropathie mit Carbamazepin (Tegretol): Doppel-Blind-Austausch-Untersuchung

Zusammenfassung An 30 Diabetikern, die unterschiedliche Formen einer peripheren diabetischen Neuropathie aufwiesen, wurde eine Doppel-Blind-Austausch-Untersuchung mit Carbamazepin und einem Plazebo-Präparat durchgeführt. Bei 28 der Patienten führt die aktive Droge zu einer symptomatischen Besserung sämtlicher Symptome von Seiten des sensiblen Nevensystems. Die Wirkung von Carbamazepin auf die motorischen und visceralen Erscheinungsformen der Neuropathie wurde nicht geprüft. Es traten zwei komplette Therapie-Versager auf. Nebenwirkungen waren häufig festzustellen; sie waren jedoch gewöhnlich leicht und klangen schnell ab. Bei zwei Patienten zwang das Auftreten eines Exanthems zum Absetzen des Präparates.

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Traitement symptomatique de la neuropathie diabétique périphérique avec la carbamazépine (Tégrétol^®): Essaidouble aveugle en cross over

Résumé Une étude de cross over double aveugle avec placebo et carbamazépine a été effectuée chez 30 patients diabétiques présentant divers types cliniques de neuropathie diabétique périphérique. La drogue active apportait un soulagement symptomatique de toutes les manifestations sensorielles dans 28 cas. Aucun effort n'a été fait pour évaluer l'action de la carbamazépine sur les manifestations motrices ou viscérales de la neuropathie. Il y eut deux échecs complets. Les effets secondaires étaient fréquents, mais en général légers et temporaires. Deux patients présentèrent une éruption qui nécessita l'arrêt du traitement.

     

Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis,assessment and management

Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co‐morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti‐depressants, the selective serotonin and noradrenaline re‐uptake inhibitors, anti‐convulsants, opiates, membrane stabilizers, the anti‐oxidant alpha‐lipoic acid and topical agents including capsaicin. Current first‐line therapies for painful DPN include tricyclic anti‐depressants, the serotonin and noradrenaline re‐uptake inhibitor duloxetine and the anti‐convulsants pregabalin and gabapentin. When prescribing any of these agents, other co‐morbidities and costs must be taken into account. Second‐line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone‐controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long‐term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non‐pharmacological approaches. Copyright © 2011 John Wiley & Sons, Ltd.     

Inhibitory effect of troglitazone on diabetic neuropathy in streptozotocin-induced diabetic rats

Summary Free-radical scavengers and inhibitors of tumour necrosis factor-α (TNF-α) such as N-acetylcysteine and pentoxifylline have been shown to inhibit the development of peripheral neuropathy in streptozotocin(STZ)-induced diabetic rats. In this study we examined the effect of troglitazone, an anti-diabetic thiazolidinedione, on diabetic neuropathy, since it also is a free-radical scavenger and a TNF-α inhibitor. Rats were fed powder chow mixed with troglitazone at 0.5 % and 0.125 % ad libitum. Although blood glucose concentrations were remarkably higher and body weight lower in diabetic than in nondiabetic rats, troglitazone had no effect on these throughout the 24-week experiment. Serum lipoperoxide concentrations, tibial nerve lipoperoxide content and serum TNF-α activity induced by lipopolysaccharide was increased in diabetic rats, but inhibited in troglitazone-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve slowed in diabetic rats, compared with that in nondiabetic rats. On the other hand, the slowed MNCV was (p < 0.05–0.01) inhibited after weeks 12 and 16 of the experiment in diabetic rats treated with high and low doses of troglitazone, respectively. Morphometric analysis showed that troglitazone suppressed the decrease of the myelinated fibre area (p < 0.05), axon/myelin ratio (p < 0.01) and fascicular area (p < 0.05) and suppressed the increase of myelinated fibre density (p < 0.001) in diabetic rats. These results indicate that troglitazone has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats irrespective of blood glucose concentrations. [Diabetologia (1998) 41: 1321–1326] Received: 16 March 1998 and in revised form: 8 June 1998     

2型糖尿病周围神经病变与尿微量白蛋白排泄率相互关系研究

目的了解糖尿病周围神经病变(DPN)有关的危险因素。方法2004-012004-06对白求恩国际和平医院的2型糖尿病(DM)患者214例,按有无合并周围神经病变进行分组,对相关因素年龄、性别、体重指数、腰臀比、病程、血压、血糖、尿白蛋白排泄率、血脂等进行单因素及Logistic多因素回归分析。结果Logistic多因素回归分析显示DPN与尿微量白蛋白排泄率(UAER)、空腹血糖(FBG)密切相关。结论在众多与DPN相关因素中UAER、FBG是两个相对独立危险因素,积极控制相关危险因素,可延缓DPN的发生发展。     

The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy

Summary Cross-sectional studies have shown plasma cell adhesion molecules (CAMs) to be increased in patients with diabetes-related complications. In the first prospective study of CAMs, we have shown that plasma CAMs may be a predictor of the development of diabetic neuropathy. We followed up 28 diabetic patients (13 neuropathic) over a 5 year period, starting from 1991. All patients had peroneal nerve conduction velocity (PNCV), vibration perception threshold and plasma CAMs measured at baseline and follow-up. We found P-selectin and intercellular adhesion molecule –1 (ICAM-1) to be increased at baseline in patients with neuropathy compared to non-neuropathic patients. P-selectin and E-selectin were also found to be significantly higher at baseline in patients who at follow-up showed deterioration in PNCV of more than 3 m/s (p < 0.05; p = 0.01; respectively). P-selectin and ICAM-1 strongly correlated with PNCV. Univariate and multivariate regression analyses showed a significant inverse association between increasing log P-selectin, log E-selectin and log ICAM-1 with decreasing PNCV, and remained significant even after adjustment for glycaemic control. P-selectin and E-selectin, odds ratios of 8.8 (95 %CI: 1.1–68.8; p = 0.038) and 12.5 (95 % CI: 1.2–132.1; p = 0.036), respectively, were significantly associated with the risk of deterioration of PNCV after 5 years. This study suggests that plasma cell adhesion molecules may play an important role in the development and progression of peripheral neuropathy in diabetes mellitus. [Diabetologia (1998) 41: 330–336] Received: 15 July 1997 and in revised form: 13 October 1997     

糖尿病周围神经病变生物学标志物的临床研究进展

糖尿病周围神经病变（DPN）是糖尿病最常见的慢性并发症之一,可导致足部溃疡、坏疽,甚至截肢,对患者的生活质量造成极大影响。DPN的发病机制复杂。近年来,针对DPN发病各个环节的生物学标志物的研究取得了一定进展。本文以DPN的病理生理改变及发病机制为出发点,主要从神经组织损伤、内皮功能紊乱、氧化应激和炎症4个方面综述DPN的潜在生物学标志物。     

Ganglioside treatment in diabetic peripheral neuropathy: A multicenter trial

Summary Ganglioside treatment was evaluated with a multicenter, randomized, double-blind, controlled, cross-overvs placebo trial in 140 insulin-treated diabetic subjects with peripheral neuropathy. The patients entered the study when they showed an impairment in at least two of the electroneurographic parameters, and were assigned to two protocols according to the presence and severity of their neurological symptoms. Ninety-seven diabetic subjects with no or mild symptoms were assigned to protocol I, whereas 43 symptomatic patients were assigned to protocol II. The treatment periods lasted 6 weeks with an intermediate washout period of 4 weeks. The treatment consisted in the daily i.m. administration of 20 mg gangliosides or of placebo. Electroneurographic parameters were recorded at the beginning and at the end of each treatment period, whereas clinical and metabolic data (mean daily plasma glucose, glycosuria and glycosylated hemoglobin) were evaluated every three weeks in protocol I and every two weeks in protocol II. No change in the metabolic parameters was observed throughout the trial period. However, the treatment induced a statistically significant improvement of paresthesias (protocol II) and of some electrophysiological parameters; in particular, ganglioside treatment improved MCV of peroneal nerve (p<0.03) in patients of protocol I, MCV of ulnar nerve (p<0.002) and SCV of median nerve (p<0.06) in patients of protocol II. Furthermore, 22 subjects of protocol II showed a ‘drug preference’ while 10 preferred placebo and 9 had no preference. In conclusion, ganglioside treatment seems to have a positive effect on diabetic peripheral neuropathy, improving both some symptoms and some electrophysiological parameters.     

Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat

Summary It has been shown that parameters of oxidative stress are increased in experimental diabetic neuropathy. The glutathione redox system is one of the intracellular scavenger systems for neutralizing free oxygen radicals. In this investigation we studied the effect of glutathione-treatment on the development of diabetic neuropathy in streptozotocin-induced diabetic rats by measuring sensory and motor nerve conduction velocities. The total study period was 10 weeks. Four groups of rats were studied: Group 1 consisted of non-diabetic, age-matched control rats; Group 2, of diabetic rats treated with placebo from week 0 to 10; Group 3, of diabetic rats treated with 200 mg glutathione/kg body weight i. v. two times per week from weeks 0 to 10; and Group 4, of diabetic rats treated with placebo from weeks 0 to 4 and as Group 3 from weeks 4 to 10. The sensory and motor nerve conduction velocity of rats treated prophylactically with glutathione (Group 3) were significantly different from those of rats treated with placebo (Group 2) or with glutathione administered at a later time point (Group 4). Complete restoration of sensory and motor nerve conduction velocity was not reached. There was a significant improvement in motor nerve conduction velocity from weeks 4 to 6 (p<0.005), but not in sensory nerve conduction velocity in the delayed treatment group (Group 4). In conclusion, treatment with glutathione, a free radical scavenger, is partially effective in the prevention of diabetic neuropathy in streptozotocin-induced diabetic rats, but is of limited value when the neuropathy is already present.     

鼠神经生长因子联合电子温针治疗糖尿病周围神经病变的疗效观察

目的观察鼠神经生长因子联合电子温针治疗糖尿病周围神经病变(Diabetic perineuropathy,DPN)的临床疗效。方法 50例DPN患者随机分为A、B 2组,A组为鼠源性神经生长因子+电子温针治疗组,B组为单纯甲钴胺治疗组,观察两组治疗前后的临床疗效、运动神经传导速度(MNCV)、感觉神经传导速度(SNCV)的改善情况、多伦多临床评分系统(Toronto clinical scoring system,TCSS)的评分情况及不良反应发生情况。结果 A组总有效率为88.00%,高于B组52.00%,差异具有统计学意义(P0.01);2组治疗前后MNCV、SNCV较治疗前均改善,差异有统计学意义(P0.05);治疗后A组改善情况优于B组,差异有统计学意义(P0.05);2组治疗前后TCSS评分均明显降低,差异有统计学意义(P0.01),治疗后A组改善情况优于B组,差异有统计学意义(P0.05)。结论鼠神经生长因子联合电子温针治疗DPN变疗效确切,是治疗DPN的一种较好的方法,值得在临床上推广应用。     

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.     

C-peptide improves neuropathy in type 1 diabetic BB/Wor-rats

BACKGROUND: The spontaneously diabetic BB/Wor-rat is a close model of human type 1 diabetes and develops diabetic polyneuropathy (DPN) similar to that seen in type 1 patients. Here we examine the therapeutic effects of C-peptide, delivered as continuous infusion or once daily subcutaneous injections on established DPN. METHODS: Diabetic rats were treated from four to seven months duration of diabetes with full continuous replacement dose of rat C-peptide via (a) osmopumps (OS), (b) full replacement dose (HSC) or (c) one-third of full replacement dose (LSC) by once daily injections. RESULTS: Diabetic rats treated with OS showed improvements in motor nerve conduction velocity (p < 0.001), sural nerve myelinated fibre number (p < 0.005), size (p < 0.05), axonal area (p < 0.001), regeneration (p < 0.001) and overall neuropathy score (p < 0.001). The progressive decline in sensory nerve conduction velocity was fully prevented. The frequencies of Wallerian degeneration were decreased (p < 0.005). HSC-treated rats showed prevention of further progression of DPN (p < 0.001), whereas LSC-treated rats showed a milder progression of DPN (p < 0.001) compared to untreated rats as assessed by neuropathy score. CONCLUSION: We conclude that (1) C-peptide is effective in the treatment of established DPN, (2) its effect is dose-dependent and (3) replacement by continuous infusion is the most effective administration of C-peptide.     

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.     

Ethnic differences in plantar pressures in diabetic patients with peripheral neuropathy

Aims To compare plantar foot pressures between Caucasian and Hispanic diabetic patients with peripheral neuropathy (PN) without a history of foot ulceration and between Caucasian and Hispanic non-diabetic individuals. Methods Forty-four Hispanic diabetic patients with PN (HDPN), 35 Caucasian diabetic patients with PN (CDPN), 41 non-diabetic Hispanic subjects and 33 non-diabetic Caucasian subjects participated. Total and regional peak plantar pressures (PPs) and pressure time integrals (PTIs) were assessed using the EMED-SF-4 plantar pressure system. Results Hispanic diabetic patients with PN had significantly lower peak PP than Caucasian diabetic patients with PN in the entire foot (552.4 ± 227.9 vs. 810.1 ± 274.6 kPa; P < 0.001), forefoot (464.1 ± 222.6 vs. 699.6 ± 323.1 kPa; P < 0.001), hindfoot (296.3.4 + 101.8 vs. 398.1 + 178.3 kPa; P < 0.01) and at the fifth metatarsal head (MTH5; 204.3 ± 143.2 vs. 388.2 ± 273.9 kPa; P < 0.001). The PTI in the entire foot, forefoot and MTH5 were also lower in HDPN than in CDPN. The ethnic differences between the diabetic groups with PN for the entire foot, forefoot and MTH5 remained significant after adjusting for the effect of age, gender, weight and duration of diabetes. There were no significant differences in peak PP and PTI among non-diabetic individuals, except for a lower peak PP at the MTH5 in Hispanic compared with Caucasian subjects. Conclusions Despite a well-known higher incidence of foot complications in diabetic Hispanic subjects, dynamic plantar pressures are lower in Hispanic diabetic patients with PN when compared with their Caucasian counterparts, suggesting that differences in other risk factors exist between these two ethnic groups.     

2型糖尿病踝肱指数与周围神经病变的关系：427例临床分析

目的探讨2型糖尿病患者踝肱指数与糖尿病周围神经病变（DPN）之间的关系。方法对427例2型糖尿病患者采用多普勒血流探测仪测定踝肱指数（ABI）,并依据ABI分为,周围动脉病变（PAD）组（ABI〈0．9）和非PAD组（ABI≥0．9）,同时检测所有患者胫后感觉神经传导速度（NCV）、潜伏期、振幅,进行组间比较,并对上述指标进行线性相关分析及多元线性回归。结果ABI〈0．9者115例,占26．9％,与非PAD组比较,PAD组周围NCV明显下降【左NCV：（30±8）VS（32±7）m／s,右NCV：（29±6）VS（33±7）m／s,P〈0．01],潜伏期延长[左潜伏期：（8．2±2．0）VS（7．4±1．4）ms,右潜伏期：（8．3±1．7）w（7．4±1．3）ms,P〈0．01],振幅下降[左振幅：（10±12）vs（15±16）mV,右振幅：（9±7）vs（14±13）mV,P〈0．011;相关分析显示,踝肱指数与潜伏期呈负相关、与振幅呈正相关;在调整年龄、病程、体质量指数（BMI）、收缩压、总胆固醇、低密度脂蛋白胆固醇（LDL．C）、血肌酐、NCV和振幅,多元逐步回归提示,ABI与年龄、LDL．C、NCV、BMI相关。结论2型糖尿病患者中,PAD可能是DPN的重要危险因素或影响因素。     

老年糖尿病周围神经病变的相关危险因素研究

目的探讨老年糖尿病周围神经病变(diabetic peripheral neuropathy,DNP)的相关危险因素。方法将89例老年糖尿病患者按是否合并周围神经病变分为病变组与对照组,观察2组体质量指数(BMI)、腰臀比(WHR)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC),高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及末梢神经功能、下肢血管超声等指标并进行比较分析。结果病变组WHR、LDL-C、下肢血管损伤程度均较对照组升高(P<0.05),神经传导速度、HDL-C较对照组降低(P<0.05),多元回归分析提示DNP与HbA1c、LDL-C、TG、血管病变负相关,与HDL-C正相关。结论DNP的发生与血糖、血脂及血管病变有关。