Effect of cinepazide combined with mecobalamine on nerve conduction velocity, vibration perception threshold and serum indexes in patients with diabetic peripheral neuropathy

Objective:To analyze the effect of cinepazide combined with mecobalamine on nerve conduction velocity, vibration perception threshold and serum indexes in patients with diabetic peripheral neuropathy. Methods:90 patients with diabetic peripheral neuropathy treated in our hospital between March 2013 and March 2016 were selected and divided into observation group and control group (n=45) according to random number table, control group received mecobalamine treatment alone and observation group accepted the cinepazide combined with mecobalamine therapy. Differences in nerve conduction velocity, vibration perception threshold as well as serum oxidative stress indexes and nerve injury marker molecules were compared between two groups of patients 2 weeks after treatment. Results:2 weeks after treatment, median nerve, ulnar nerve and peroneal nerve sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) levels of observation group were higher than those of control group (P<0.05) while both lower extremities vibration perception threshold (VPT) levels were lower than those of control group (P<0.05). Serum homocysteine (HCY), advanced glycosylation end products (AGEs), malondialdehyde (MDA), neuron-specific enolase (NSE), high mobility group B1 (HMGB1) and S100βcontent of observation group were lower than those of control group (P<0.05) while reduced glutathione (GSH), superoxide dismutase (SOD), myelin basic protein (MBP) and brain-derived neurotrophic factor (BDNF) content were higher than those of control group (P<0.05). Conclusions:Cinepazide combined with mecobalamine can reduce the nerve injury degree, improve nerve conduction and vibration perception and alleviate the oxidative stress degree in patients with diabetic peripheral neuropathy.

Influence ofα-Lipoic acid adjuvant therapy on sugar metabolism,peripheral nerve conduction velocity and oxidative stress in patients with diabetic peripheral neuropathy

Objective: To explore the influence of α-Lipoic acid adjuvant therapy on glucose metabolism, peripheral nerve conduction velocity and oxidative stress in patients with diabetic peripheral neuropathy. Methods: A total of 92 cases of patients with diabetic peripheral neuropathy were divided into observation group and control group according to the odd and even admission number, 46 cases in each group. All patients were given the conventional treatment, on this basis, patients in control group were given orally Pancreatic Kinionoge, patients in observation group were given α-Lipoic acid intravenous injection. They were treated for 14 d. The following indicators were observed in two groups before and after treatment: glucose metabolic index: fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG) and glycosylated hemoglobin (HbA1c);peripheral nerve conduction velocity, median nerve, sensory nerve conduction velocity of nervus peroneus communis (MCV) and motor nerve conduction velocity (SCV), ankle arm index (ABI) and inner diameter of lower limb artery (femoral artery, dorsalis pedis artery, popliteal artery), oxidative stress indicators: superoxide dismutase (SOD) and malondialdehyde (MDA). Results: Compared with before treatment, the FBG, 2hPBG, HbA1c level in two groups after treatment were significantly reduced, but the difference of intergroup after treatment was no statistical significance;MCV and SCV of median nerve and nervus peroneus communis was increased significantly than control group after treatment, moreover MCV and SCV of median nerve and nervus peroneus communis in observation group were higher than control group after treatment, the difference was significant. After treatment, ABI and femoral artery, dorsalis pedis arteries, popliteal artery inner diameter in two groups were increased significantly, moreover after treatment the above level in observation group was obviously higher than control group, there was significant difference. After treatment, the MDA in observation group were reduced significantly and SOD level increased significantly, difference was statistically significant compared with before treatment and control group after the treatment;The difference in control group compared between before treatment and after treatment had no statistical significance. Conclusion: Diabetic peripheral neuropathy treated adjuvantly by α-Lipoic acid can significantly improve lower limb blood supply, improve the peripheral nerve conduction velocity, reduce level of oxidative stress, the effect on glucose metabolism still need long course of observation.

Effects of pestle needle on nerve conduction velocity and inflammatory injury in patients with diabetic peripheral neuropathy

Background:Diabetic peripheral neuropathy(DPN)is one of the most common complications of diabetes mellitus.Impaired neurological function is one of the main characteristics of DPN and is strongly associated with the inflammatory response.Our previous studies have confirmed that pestle needle can improve the nerve function of patients with DPN.But the mechanism of pestle needle treatment of DPN is still unclear.Methods:A total of 70 DPN patients who met the inclusion criteria were randomly divided into two groups.Control group(CG)(n=35)received DPN conventional treatment and the pestle needle group(PNG)(n=35)received pestle needle therapy at Zhiyang(DU09)eight array,Mingmen(DU04)eight array and Heche Road(from Mingmen(DU04)to Changqiang(DU01)),Zusanli(ST36),Sanyinjiao(SP06),Taixi(KI03)and Yongquan(KI01).Patients in the PNG group were required to take this treatment for 4 weeks,5 times a week.Examination indexes were collected before and after treatment,respectively.Nerve function was examined using the Toronto clinical scoring system and nerve conduction velocity detection.Serum inflammatory factors were measured by enzyme linked immunosorbent assay.Results:The Toronto clinical scoring system was significantly reduced in the PNG compared with the CG after treatment.The sensory nerve conduction velocity and motor nerve conduction velocity of the right peroneal and median nerves were significantly faster in the PNG than those in the CG(P<0.05).After treatment,serum interleukin-1 beta,interleukin-6 and tumor necrosis factor-alpha levels decreased in both groups,and the improvement of PNG was better than CG(P<0.05).Conclusion:The pestle needle can significantly improve the symptoms and nerve conduction velocity of DPN,and its mechanism may be related to the reduction of inflammatory factors.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Autophagy-targeting modulation to promote peripheral nerve regeneration

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy:an analysis of 500 cases

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013：221 cases showed symptoms of peripheral neuropathy （symptomatic group） and 279 cases had no symptoms of peripheral impairment （asymptomatic group）. One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases （71.6%）, among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

Relationship between sonographically measured median nerve cross-sectional area and presence of peripheral neuropathy in diabetic subjects

BACKGROUND Neuropathy is a common complication of diabetes mellitus resulting from direct damage by hyperglycemia to the nerves and/or ischemia by microvascular injury to the endoneurial vessels which supply the nerves. Median nerve is one of the peripheral nerves commonly affected in diabetic neuropathy. The median nerve size has been studied in non-Nigerian diabetic populations. In attempt to contribute to existing literature, a study in a Nigerian population is needed.AIM To evaluate the cross-sectional area(CSA) of the median nerve using B-mode ultrasonography(USS) and the presence of peripheral neuropathy(PN) in a cohort of adult diabetic Nigerians.METHODS Demographic and anthropometric data of 85 adult diabetes mellitus(DM) and 85 age-and sex-matched apparently healthy control(HC) subjects were taken. A complete physical examination was performed on all study subjects to determine the presence of PN and modified Michigan Neuropathy Screening Instrument(MNSI) was used to grade its severity. Venous blood was taken from the study subjects for fasting lipid profile(FLP), fasting blood glucose(FBG) and glycated haemoglobin(HbA1 c) while their MN CSA was evaluated at a point 5 cm proximal to(5 cmCATL) and at the carpal tunnel(CATL) by high-resolution Bmode USS. Data was analysed using SPSS version 22.RESULTS The mean MN CSA was significantly thicker in DM subjects compared to the HC at 5 cmCATL(P < 0.01) and at the CATL(P < 0.01) on both sides. The presence of diabetic peripheral neuropathy(DPN) further increased the MN CSA at the CATL(P < 0.05) but not at 5 cmCATL(P > 0.05). However, the severity of DPN had no additional effect on MN CSA 5 cm proximal to and at the CATL. There was no significant association between MN CSA and duration of DM and glycemic control.CONCLUSION Thickening of the MN CSA at 5 cmCATL and CATL is seen in DM. Presence of DPN is associated with worse thickening of the MN CSA at the CATL but not at5 cmCATL. Severity of DPN, duration of DM, and glycemic control had no additional effect on the MN CSA.

Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 m L/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test（indicating an improved ability to maintain body position）, prolonged tail-flick latency and foot-licking time（indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds）, and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus.

Microsurgical decompression of the median nerves for treating diabetic peripheral neuropathy in the upper limbs: A 21-month follow-up

BACKGROUND： Peripheral nerve injured by abnormal glucose metabolism is compressed, which is an important etiological factor of diabetic peripheral neuropathy （DPN）. Microsurgical decompression of peripheral nerve maybe effectively releases the symptoms of DPN. OBJECTIVE： To investigate the curative effects of microsurgical decompression of median nerves for treatment of DPN in upper limbs. DESIGN： Case-follow up observation. SETTING： Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Health. PARTICIPANTS： Twelve patients with DPN in upper limbs （19 hands） who received treatment in the Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Public Health between March 2004 and July 2006 were involved in this experiment. The involved patients, 5 male and 7 female, were aged 44 to 77 years, with DPN course of 6 months to 16 years. They all met 1999 WHO diabetic diagnosis criteria. Both two hands had symptom in 7 patients, and only one hand had symptom in 5 patients. Informed consents of detected items were obtained from all the patients, who also received 21 months of follow-up treatment. METHODS： （1）Operation was carried out under the anesthetic status of brachial plexus. Under an operating microscope, transverse carpal ligament was exposed. Subsequently, transverse carpal ligament, forearm superficial fascia and palmar aponeurosis were fully liberated, and then part of them was cut off. Connective tissue around median nerve, superficial flexor muscle of fingers, radial flexor, palmaris longus and other flexor tendons were completely loosened. Finally, epineurium was opened with microinstrument for neurolysis. After tourniquet was loosened, and bipolar coagulator was used to stop bleeding, and the incision was closed. （2） In postoperative 21 months, the subjective symptom, two-point discrimination （The smallest distance of two normal points was 3 to 6 mm）, nerve conduction velocity and action potential amplitude （short abductor muscle of thumb end Lat 〈 4.5 ms; Motor nerve conduction velocity of forearm 〉 50 m/s）, etc. of all the patients were followed up. MAIN OUTCOME MEASURES＂ The objective evaluation and long-term follow up of curative effect of microsurgical decompression of median nerves for treatment of DPN in upper limbs. RESULTS： Twelve patients with DPN in upper limbs participated in the final analysis. （1） After operation, numbness and pain symptom releasing 100% were found in 19 hands of 12 patients with DPN. During follow up, numbness and recrudescent pain symptom were found in one hand （5%, 1/19）. （2）Postoperatively, index finger two point discrimination in 15 （94%, 15/16） hands recovered to normal. （3） nerve conduction velocity and action potential amplitude improved completely. （4） Two hands （2/19, 10% ）had poor healing at incision, and they late healed at postoperative 1 and 1.5 months, respectively. CONCLUSION： Long-term follow-up results show that microsurgical decompression is an effective method to treat DPN in upper limbs.

Abnormality of peripheral nerve conduction velocity associated with illness course, symptoms and fasting blood glucose in patients with type 2 diabetes mellitus

BACKGROUND: It has shown that abnormality of peripheral nerve conduction velocity during onset of diabetes mellitus is not related to age and sex, but to symptoms, illness course and level of fasting blood glucose. OBJECTIVE: To measure correlation of abnormality of peripheral nerve conduction velocity with various illness courses, symptoms and levels of fasting blood glucose of patients with type 2 diabetes mellitus. DESIGN: Case analysis. SETTING: Department of Neurology, Central People's Hospital of Huizhou. PARTICIPANTS: A total of 128 patients who were diagnosed as type 2 diabetes mellitus were selected from Central People's Hospital of Huizhou from September 2001 to October 2005. There were 75 males and 53 females aged 32-83 years and the illness course ranged from 1 month to 20 years. METHODS: All 128 patients with type 2 diabetes mellitus received neuro-electrophysiological study and their clinical data were retrospectively analyzed to measure peripheral nerve conduction velocity and fasting blood glucose so as to investigate the correlation of peripheral nerve conduction velocity with clinical symptoms, illness course and levels of fasting blood glucose. MAIN OUTCOME MEASURES: Correlation of peripheral nerve conduction velocity with clinical symptoms, illness course and levels of fasting blood glucose. RESULTS: All 128 patients with type 2 diabetes mellitus were involved in the final analysis. ① Among 128 patients, 114 patients had abnormality of peripheral nerve conduction velocity; 110 patients had clinical symptoms, including 102 patients having abnormality of peripheral nerve conduction velocity; 18 patients did not have clinical symptoms, including 12 patients having abnormality of peripheral nerve conduction velocity. There were significant differences between them (χ 2=8.275, P =0.04). ② Among 128 patients, illness course of 75 patients was equal to or less than 5 years, including 27 patients having abnormality of peripheral nerve conduction velocity; illness course of 53 patients was more than 5 years, including 35 patients having abnormality of peripheral nerve conduction velocity. There were significant differences between them (χ 2=11.469, P =0.003). ③ Among 128 patients, levels of fasting blood glucose of 75 patients was equal to or lower than 11 mmol/L, including 41 patients having abnormality of peripheral nerve conduction velocity; levels of fasting blood glucose of 53 patients was higher than 11 mmol/L, including 38 patients having abnormality of peripheral nerve conduction velocity. There were significant differences between them (χ 2=4.023, P =0.134). CONCLUSION: ① Abnormality of peripheral nerve conduction velocity of patients with type 2 diabetes mellitus is related to illness courses and clinical symptoms. The longer the illness course is, the severer the abnormality of peripheral nerve conduction velocity is. Abnormality of peripheral nerve conduction velocity always occurs on patients who have clinical symptoms. ② Abnormality of peripheral nerve conduction velocity is not related to levels of fasting blood glucose.

Expression of ceramide galactosy transferase in sciatic nerve of rats with diabetic peripheral neuropathy after electroacupuncture at Zusanli and Shenshu points

BACKGROUND： Ceramide galactosyltransferase （CGT） protein and mRNA expression defect can cause the abnormal morphology and slowing conduction velocity of peripheral nerve. Morphologic change and functional disorder of myelin sheath and axon appear when diabetic peripheral neuropathy （DPN） occurs. Whether electroacupuncture at Zusanfi（ST 36） and Shenshu（BL 32） points can enhance the expression of CGT protein and mRNA in the DPN tissue？ OBJECTIVE： To observe the effect of electroacupuncture at Zusanfi and Shenshu points on motor, sensory conduction velocity and CGT mRNA and its protein expression of sciatic nerve in rats with DPN. DESIGN： A randomized and controlled animal experiment SETTING ： Department of Neurology and Central Laboratory, Yueyang Hospital of Traditional Chinese ＆ Western Medicine, Shanghai University of Traditional Chinese Medicine. MATERIALS ： Totally 60 healthy male Wistar rats of clean grade, aged 4 month, with body mass of 200 to 220 g, were enrolled in this study. Streptozotocin （STZ, Sigma Company of USA, Batch No. S-0130）. METHODS： This study was carried out in the Animal Experimental Center and Central Laboratory, Yueyang Hospital of Traditional Chinese ＆ Western Medicine during February 2005 to March 2006. （1） Fifteen rats were randomly chosen,serving as normal group.AU the other rats were intraperitoneally injected once with STZ to develop experimental diabetic rat models. If fasting blood glucose was ≥ 15 mmol/L,sensory nerve and motor nerve conduction velocity of sciatic nerve was obviously slowed, tail-swaying temperature threshold was increased and myelinated nerve fiber of sciatic nerve changed, DPN models were successful. The successful model rats were randomly assigned into 3 groups： model group, control group（electroacupuncture at non-meridian-non-acupoint）and electroacupuncture group [electroacupuncture at Zusan/i and Shenshu points], with 15 rats each. The rats in the normal group and model group were untouched. In the electroacupuncture group （electroacupuncture at Zusanfi and Shenshu points）, Shenshu point （double） and Zusanfi point （double） were chosen referencing to The Atlas of the Rat＇s Acupoints. G6805- Ⅱ electric acupuncture apparatus was used, and current intensity was controlled at 20 min/time, once every other day, 12 times within 24 days. In the control group, the tip of rat-tail was stimulated, and the concrete procedures were the same as in the electroacupuncture at Zusanfi and Shenshu points. （2） Motor nerve conduction velocity and sensory nerve conduction velocity of rats were detected with neuroelectrophysiology detector in the end of the treatment, and the expressions of CGT protein and mRNA of sciatic nerve were detected with immunohistochemical method and fluorescent quantitative PCR technique. MAIN OUTCOME MEASURES： （1） Motor and sensory nerve conduction velocity. （2） The expression of CGT protein and its mRNA. RESULTS： All the 60 rats entered the stage of result analysis. （1） Comparison of motor and sensory nerve conduction velocity of rats after electroacupuncture： Motor nerve conduction velocity of rats in the model group[（31.37±3.69） m/s], control group [（32.74±5.42） m/s] and electroacupuncture group [（41.30 ±1.15） m/s] was significantly lower than that in the normal group [（41.30±1.15） m/s, P 〈 0.01]; The sensory nerve conduction velocity of rats in the model group[（18.17±9.54） m/s], control group [（21.39±5.61） m/s]and electroacupuncture group [（35.81 ±4.59） m/s] was significantly lower than that in the normal group [（46.38± 6.32） m/s,P 〈 0.01]; The motor and sensory nerve conduction velocity of electroacupuncture group was significantly higher than that in the model group [（38.04±2.01） m/s vs. （32.74±5.42） m/s,（35.81±4.59） m/s vs. （21.39±5.61） m/s,P 〈 0.01]. （2） Comparison of the expression of CGT protein of sciatic nerve of rats： The number of CGT positive cells of sciatic nerve in model group, control group or electroacupuncture group was significantly smaller than that in normal group [（9 770.33±1 461.73）, （10 588.13±1119.52）, （27 518.27± 9 078.29）, （37 769.67±4 021.81）/μm^2,P 〈 0.01]; The number of CGT positive cells of the sciatic nerve in the electroacupuncture group was significantly larger than that in the model group and control group （P 〈 0.01）. The number of CGT positive cells of sciatic nerve was close between control group and electroacupuncture group （P 〉 0.05）. （3） Comparison of CGT mRNA expression of sciatic nerve of rats： Ct value of CGT mRNA of sciatic nerve of rats in the model group,control group and electroacupuncture group was significantly higher than that in the normal group （13.75±2.60,14.81±2.80,11.67±1.75,9.30±0.98, P 〈 0.01 ）; Ct value of CGT mRNA of sciatic nerve of rats in the electroacupuncture group was significantly lower than that in the model group and control group （P 〈 0.01）, and that was close between electroacupuncture group and control group （P 〉 0.05）. CONCLUSION ： Electroacupuncture at Zusanfi and Shenshu points can increase motor and sensory nerve conduction velocity of rats with DPN. It might be associated with up-regulating the expression of CGT mRNA and its protein.

A Meta analysis of characteristics of median nerve and sural nerve injury inpatients with diabetic peripheral neuropathy

Objective： A meta-analysis of randomized trials was performed to assess the injured degree of median nerve andsural nerve in patients with diabetic peripheral neuropathy （DPN）. Methods： we searched Pubmed Database, ChinaBiomedical Literature Database, VIP Database, ChinaNet for studies. Then evaluated these studies in order to findthe researches in line with the requirements of the study; Each relevant research was carefully read to extractrelevant data; The current perception threshold （CPT） value of median nerve and sural nerve were compared at2000Hz, 250Hz and 5Hz between patients with DPN and the normal control group. Results： Finally 10 articles thatmeet the standards were included, with 1054 cases in the patient group and 719 cases in the normal group. The CPTvalues of median nerve and sural nerve at 2000 Hz, 250 Hz and 5 Hz of patients group were higher than those ofnormal control group （P 〈0.05 for all）. Conclusion： Systematic reviews showed that the sensitivity of the mediannerve and sural nerve in DPN patients was generally reduced. Sensory nerve quantitative detector could detectnerve damage early, accurately and monitor the effect treatment in patients with DPN.

CLINICAL AND ELECTROPHYSIOLOGICAL OBSERVATIONS ON DIABETIC PERIPHERAL NEUROPATHYTREATED BY WARM NEEDLING AND MOXIBUSTION

Objective To observe clinical therapeutic effects of warm needling and moxibustion on diabetic peripheral neuropathy （DPN） and their influence on nerve conduction velocity. Methods Fifty two cases were randomly divided into a treatment group （n =26） and a control group （n =26）. In addition to basic treatment for lowering blood sugar in both groups, Pǐshū （BL 20）, Shènshū （BL 23）, Huántiào （GB 30）, Zùsānlǐ （ST 36）, Yánglíngquán （GB 34）, Sānyīnjiāo （SP 6）, Tàixī （KI 3）, Qǔchí （LI 11）, Wàiguān （TE 5） and Hégǔ （LI 4） were selected for warm needling and moxibustion in the treatment group. Methycobal was intramuscularly injected in the control group. Clinical symptoms and conduction velocities of the tibial nerve and common peroneal nerve were compared before and after treatment. Results Warm needling and moxibustion could alleviate such clinical symptoms as numbness of limbs, pain and hypoesthesia, and obviously improve the conduction velocities of both tibial and common peroneal nerves. Conclusion Warm needling and moxibustion exhibit good therapeutic effects on diabetic peripheral neuropathy.

Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy：a meta-analysis of 16 randomized controlled trials

OBJECTIVE：This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction（HGWWD） for treating diabetic peripheral neuropathy.DATA SOURCES：Six electronic databases,including the Cochrane Library,MEDLINE database,Chinese Biomedical Database,Chinese National Knowledge Infrastructure Database,Chinese Science and Technique Journals Database,and the Wanfang Database,were search ed on the internet for randomized controlled trials published up until 1 December 2015.The search terms included ＂Chinese herbal medicine＂,＂diabetic peripheral neuropathy＂ and ＂randomized controlled trials＂ in Chinese and in English.DATA SELECTION：We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group,without restriction for the control group.We assessed literature quality in accordance with the Cochrane Review Handbook.A random or a fixed effects model was used to analyze outcomes using Rev Man 5.2 software.OUTCOME MEASURES：The primary outcomes were changes in symptoms and nerve conduction velocities.The secondary outcomeswere fasting blood glucose and hemorheological indexes.RESULTS：Sixteen randomized controlled trials,with a total of 1,173 patients,were included.Meta-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment（i.e.,control group）（risk ratio = 0.36,95% confidence interval（CI）：0.29–0.46,Z =8.33,P 〈 0.00001） Compared with the control group,there was an increase in median motor nerve conduction velocity（mean difference（MD） = 3.46,95%CI：1.88–5.04,Z = 4.30,P 〈 0.01） and median sensory nerve conduction velocity（MD = 3.30,95%CI：2.04–4.56,Z = 5.14,P 〈 0.01）.There was also an increase in peroneal motor nerve conduction velocity（MD = 3.22,95%CI：2.45–3.98,Z = 8.21,P 〈 0.01） and peroneal sensory nerve conduction velocity（MD = 3.05,95%CI：2.01–4.09,Z = 5.75,P 〈 0.01） in the treatment groups.No significant difference in fasting blood glucose was found between the treatment groups and the control groups（MD =-0.12,95%CI：-0.42–0.19,Z = 0.76,P = 0.45）.Plasma viscosity was significantly decreased after treatment（MD =-0.11,95%CI：-0.21 to-0.02,Z = 2.30,P = 0.02）.No significant difference in fibrinogen was detectable（MD =-0.53,95%CI：-1.28–0.22,Z = 1.38,P = 0.17）.Four trials reported that treatment groups experienced no adverse reactions.Adverse events were not mentioned in the other 12 trials.No trial reported the incidence of complications,quality of life outcomes,or health economics.CONCLUSION：HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities.Our study suggests that HGWWD may have significant therapeutic efficacy for the treatment of diabetic peripheral neuropathy.However,the methodological quality of the randomized controlled trials was generally low.Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.

Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway

Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.

Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials

OBJECTIVE： To evaluate the efficacy of α-lipoic acid（ALA） plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy（DPN）. DATA SOURCES： The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were（diabetic peripheral neuropathy or diabetic neuropathy or DPN） AND（α-lipoic acid or lipoic acid or thioctic acid） AND epalrestat. DATA SELECTION： All of the eligible studies met the following inclusion criteria：（1） Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.（2） The minimum duration of treatment was 2 weeks.（3） The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.（4） Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES： The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity（MNCV）, median sensory nerve conduction velocity（SNCV）, peroneal MNCV and peroneal SNCV.RESULTS： Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies（RR = 1.29, 95% CI： 1.21–1.38; RR = 1.43, 95% CI： 1.34–1.54, respectively）. ALA plus epalrestat combination therapy also significantly improved median MNCV（WMD = 5.41, 95% CI： 2.07–8.75）, median SNCV（WMD = 5.87, 95% CI： 1.52–10.22）, peroneal MNCV（WMD = 5.59, 95% CI： 2.70–8.47） and peroneal SNCV（WMD = 4.57, 95% CI： 2.46–6.68）.CONCLUSION： ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

Acupuncture in diabetic peripheral neuropathy-neurological outcomes of the randomized acupuncture in diabetic peripheral neuropathy trial

BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of diabetes mellitus and can lead to serious complications.Therapeutic strategies for pain control are available but there are few approaches that influence neurological deficits such as numbness.AIM To investigate the effectiveness of acupuncture on improving neurological deficits in patients suffering from type 2 DPN.METHODS The acupuncture in DPN(ACUDPN)study was a two-armed,randomized,controlled,parallel group,open,multicenter clinical trial.Patients were randomized in a 1:1 ratio into two groups:The acupuncture group received 12 acupuncture treatments over 8 wk,and the control group was on a waiting list during the first 16 wk,before it received the same treatment as the other group.Both groups received routine care.Outcome parameters were evaluated after 8,16 and 24 wk and included neurological scores,such as an 11-point numeric rating scale(NRS)11 for hypesthesia,neuropathic pain symptom inventory(NPSI),neuropathy deficit score(NDS),neuropathy symptom score(NSS);nerve conduction studies(NCS)were assessed with a handheld point-of-care device.RESULTSSixty-two participants were included.The NRS for numbness showed a difference of 2.3(P<0.001)in favor of theacupuncture group,the effect persisted until week 16 with a difference of 2.2(P<0.001)between groups and 1.8points at week 24 compared to baseline.The NPSI was improved in the acupuncture group by 12.6 points(P<0.001)at week 8,the NSS score at week 8 with a difference of 1.3(P<0.001);the NDS and the TNSc score improvedfor the acupuncture group in week 8,with a difference of 2.0 points(P<0.001)compared to the control group.Effects were persistent in week 16 with a difference of 1.8 points(P<0.05).The NCS showed no meaningfulchanges.In both groups only minor side effects were reported.CONCLUSION Study results suggest that acupuncture may be beneficial in type 2 diabetic DPN and seems to lead to a reductionin neurological deficits.No serious adverse events were recorded and the adherence to treatment was high.Confirmatory randomized sham-controlled clinical studies with adequate patient numbers are needed to confirmthe results.

Effects of selenium on electrophysiological changes associated with diabetic peripheral neuropathy

Our previous study has demonstrated that sodium selenite prevents oxidative stress, suggesting that selenium can improve diabetic peripheral neuropathy. Results from this study demonstrated that diabetes mellitus resulted in significant increased time to peak, as well as rheobase and chronaxie values. In addition, maximum depolarization, area under compound action potential, kinetics, and conduction velocities of fast and slow nerve fiber groups were decreased. Sodium selenite exhibited positive effects on alterations of diabetes mellitus-induced conduction velocity distribution. This neuroprotective effect was primarily observed in the area under compound action potential and compound action potential kinetic waveforms, as well as rheobase and chronaxie. Results from this study showed that selenium supplementation blocked the diabetes mellitus-induced shift of actively contributing nerve fibers, and restored levels towards age-matched control group values. Chronic selenate supplementation for experimental diabetic peripheral neuropathy exhibited protective effects in measured electrophysiological parameters.

Angiogenin gene polymorphism A risk factor for diabetic peripheral neuropathy in the northern Chinese Han population?

Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se- quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus （129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa- tients） and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.