Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

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.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine

Diabetic peripheral neuropathy(DPN)is one of the strongest risk factors for diabetic foot ulcers(neuropathic ulcerations)and the existing ulcers may further deteriorate due to the damage to sensory neurons.Moreover,the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time.DPN is associated with gut microbiota dysbiosis.Traditional Chinese medicine(TCM)compounds such as Shenqi Dihuang Decoction,Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota.The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut microbiota.

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease progression.The pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not address.Furthermore,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest effect.Acupuncture is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain syndromes.In their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment cessation.Although previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are required.Overall,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

Systematic investigation of Radix Salviae for treating diabetic peripheral neuropathy disease based on network Pharmacology

BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.

Clinical Efficacy of Pentoxifylline Combined with Thioctic Acid in the Treatment of Painful Diabetic Peripheral Neuropathy

Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022 were selected and randomly grouped,with pentoxifylline+thioctic acid treatment in Group A and thioctic acid treatment in Group B,and the treatment efficacy was compared.Results:The treatment efficacy in Group A was higher than that of Group B,P<0.05;the points of each symptom of PDPN in Group A were lower than that of Group B,P<0.05;the C-reactive protein and electromyography indexes of PDPN patients in Group A were better than that of Group B,P<0.05.Conclusion:PDPN patients treated with pentoxifylline+thioctic acid can optimize nerve function,inhibit inflammation progression,and reduce PDPN symptoms,which is an efficient and feasible treatment option.

Association of comorbidities with increasing severity of peripheral neuropathy in diabetes mellitus

AIM: To analyze a large population of patients with diabetes and peripheral neuropathy(PN) to determine other meaningful comorbid etiologies for PN.METHODS: Peripheral Neuropathy is a common complication of type 1 and 2 diabetes mellitus;however,other potential causes for PN may be co-existing in patients with diabetes.A prospective cohort study was performed to assess patients with diabetes and PN.We compared patients having PN due solely to diabetes with patients possessing co-existing comorbidities,performing clinical(Toronto Clinical Scoring System and the Utah Early Neuropathy Scale),laboratory and electrophysiological assessments in all patients.RESULTS: Patients with either type 1 or 2 diabetes mellitus and co-existing comorbidities did not have more severe clinical or electrophysiological PN phenotypes overall.However,in patients with type 1 diabetes,presence of a lipid disorder was associated with greater PN severity.In type 2 diabetes patients,both a lipid disorder and cobalamin deficiency were associated with greater PN severity.There was no additive effect upon PN severity with presence of three or more comorbid etiologies.CONCLUSION: The presence of specific,and not general,comorbidities in patients with type 1 or 2 diabetes corresponds with greater PN severity.

Factors Associated with Peripheral Neuropathy in Type 2 Diabetes： Subclinical versus Confirmed Neuropathy

This study determined the prevalence of diabetic peripheral neuropathy(DPN) and subclinical DPN(s DPN) in patients with type 2 diabetes mellitus(T2DM) using nerve conduction study(NCS) as a diagnostic tool. We also investigated the factors associated with the development of s DPN and compared factors between the sD PN and confirmed DPN(cDPN). This cross-sectional study involved 240 T2DM patients who were successively admitted to the endocrinology wards of Wuhan Union Hospital over the period of January to December 2014. Data on the medical history, physical and laboratory examinations were collected. DPN was diagnosed using NCS. One-way ANOVA with least significant difference(LSD) analysis or chi-square tests was used to compare parameters among DNP-free, s DPN and c DPN patients. Independent factors associated with s DPN were determined using logistic regression. The results showed that 50.8% of the participants had DPN, and among them, 17.1% had sDPN. sDPN showed significant independent associations with age, height, HbA1c, presence of atherosclerosis and diabetic retinopathy. Patients with DPN differed significantly from those without DPN with respect to age, duration of disease(DOD), HbA1c, presence of atherosclerosis, diabetic retinopathy, nephropathy and hypertension. Patients with cDPN, relative to those with sDPN, had significantly longer DOD and higher prevalence of peripheral artery disease(PAD) and coronary artery disease(CAD). Our study suggests that a significant number of T2DM patients are affected by s DPN, and the development of this condition is associated with advanced age, tall stature, poor glycaemic control, presence of diabetic retinopathy and atherosclerosis. On the other hand, patients with cDPN tend to have a longer DOD and are more likely to suffer from PAD and CAD.

Validation of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy

Objective:This study aims to evaluate the reliability and validity of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy(PDPN).Methods:One hundred patients with PDPN and 70 patients with non-neuropathic pain were recruited from five grade III general hospitals in Guangzhou.Pain was assessed using the Leeds Assessment of Neuropathic Symptoms and Signs(LANSS),Douleur Neuropathique 4 questionnaire(DN4),and Brief Pain Inventory for Painful Diabetic Peripheral Neuropathy(BPI-DPN).Reliability was evaluated by internal consistency of the Cronbach's a coefficient and Guttman split-half.Construct validity was analyzed by factor analysis and Spearman correlation coefficients.Sensitivity and specificity were also assessed.Results:The Cronbach's a coefficients of the LANSS,DN4,and BPI-DPN were 0.735,0.750,and 0.898,respectively.The Guttman split-half coefficients of the LANSS,DN4,and BPIDPN were 0.660,0.726,and 0.849,respectively.The cumulative contributions of the LANSS,DN4,and BPI-DPN to the total variance were 61.945%,57.010%,and 66.056%,respectively.The items of the LANSS,DN4,and BPI-DPN presented high factorial loads,ranging from 0.387 to 0.841,0.137 to 0.948,and 0.487 to 0.953,respectively.The LANSS and DN4 exhibited sensitivities of 58.0%and 82.7%,respectively,and specificity of 97.1%.Conclusions:The LANSS or DN4 can be used to detect neuropathic pain in Chinese patients with PDPN.The BPI-DPN can be employed to monitor the effectiveness of pain intervention.

HLA class Ⅱ alleles and risk for peripheral neuropathy in type 2 diabetes patients

The potential impact of human leukocyte antigen （HLA） genotype variations on development of diabetic peripheral neuropathy （DPN） is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes （T2D） patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index （BMI） and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers （PCR-SSP） method. T2D patients with DPN showed higher frequencies of HLA-DRB1＊10 and DRB1＊12 alleles compared to control group （P = 0.04）. HLA-DQB1＊02 allele and HLA-DRB1＊07-DQB1＊02 haplotype were associated with a decreased risk for developing DPN in T2D patients （P = 0.02 and P = 0.05 respectively）. Also, patients with severe neuropathy showed higher frequencies of DRB1＊07 （P = 0.003） and DQB1＊02 （P = 0.02） alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB 1 and DQB 1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1＊02 allele and HLA-DRB1＊07-DQB1＊02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.

Peripheral Neuropathy and Vasculopathy;Frequency and Associated Risk Factors in Newly Diagnosed Treatment Naive Type 2 Diabetes

Background: The prevalence of diabetes in Pakistan is 11.45%. The reported prevalence of diabetic foot ulceration in Pakistan is between 4% and 10%, with the amputation rate of 8% - 21%. Peripheral neuropathy and vasculopathy are main underlying cause of diabetic foot ulcers. Methodology: It was a cross-sectional non-interventional cohort study where all newly diagnosed treatment na&#239;ve type 2 diabetic patients were enrolled. Peripheral neuropathy and vasculopathy were detected by Michigan neuropathy screening instrument (MNSI) and ankle brachial index (ABI) respectively. Risk factors for peripheral neuropathy and vasculopathy were determined by univariate and multivariate logistic regression analysis. Statistical significance was considered with P value of Result: Fifty seven patients (37.7%) had early neuropathy with MNSI score of 3.3 ± 0.4. Thirty seven patients (20.6%) had vasculopathy with ABI score of 0.76 ± 0.11. Age (Odd ratio 1.07 (1.02 - 1.11), p 0.003), duration of symptoms (Odd ratio 1.11 95% CI: 1.05 - 1.17, p ≤ 0.001), high HbA1C % (Odd ratio 1.94 95% CI: 1.54 - 2.45, P ≤ 0.001), albumin creatinine ratio (Odd ratio 1.01, 95% CI: 1.00 - 1.01, P ≤ 0.001 ) and cholesterol level (Odd ratio 1.01 95% CI: 1.01 - 1.02, p = 0.001) were found as risk factors for early neuropathy and vasculopathy. Conclusion: Peripheral neuropathy and vasculopathy are frequently reported complications among newly diagnosed treatment na&#239;ve patients of type 2 DM. Age, duration of symptoms prior to diagnosis, metabolic parameters like raised HbA1C, hyperlipidemia and spot random albumin creatinine ratio are found to be risk factors for both peripheral neuropathy and vasculopathy.

Diabetes Mellitus and Diabetic Peripheral Neuropathy

Diabetes mellitus (DM) is considered a major public health problem because of its high prevalence and progressive increase of incidence. DM chronic complications are major causes of morbidity and mortality, among which diabetic neuropathy (DN) stands out, affecting 30% - 50% of DM patients. An appropriate medical approach, involving anamnesis and thorough clinical examination, is extremely important for the early diagnosis of DN and, therefore, to the prevention of its complications, including the amputation of limbs. Despite of the importance of DN prevention and treatment, in order to provide improved quality of life and longevity to DM patients, current therapeutic options are very limited with respect to both symptom control and as effective disease therapies. Intensive glucose control is extremely important in order to prevent and avoid the progression of DN, as demonstrated in two large multicenter studies involving patients with type 1 DM, the DCCT (Diabetes Control and Complications Trial) and the EDIC (Epidemiology of Diabetes Interventions and Complications).

Effects of α-zinc sulfate combined with yiqiyangyinghuoxue therapy on related factors in patients with type 2 diabetes peripheral neuropathy

Objective: To study the effects of -zinc sulfate combined with yiqiyangyinghuoxue therapy on related factors in patients with type 2 diabetes peripheral neuropathy. Methods: A total of 90 patients with type 2 diabetes peripheral neuropathy in our hospital from September 2015 to September 2018 were enrolled in this study. The subjects were divided into the control group (n=45) and the treatment group (n=45) randomly. The control group were treated with -zinc sulfate, the treatment group were treated with -zinc sulfate combined with yiqiyangyinghuoxue therapy, the two groups were treated for 3 months. The serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before treatment. After treatment, the serum NSE, UA, Hcy, hs-CRP, HMGB1, CysC, TGF-β1, ESM-1 and plasma ET, TNF of the two groups were significantly lower than before treatment, the serum BDNF, 25-(OH)D3, NO of the two groups were significantly higher than before treatment, and that of the treatment group after treatment were significantly better than the control group. Conclusion: α-zinc sulfate combined with yiqiyangyinghuoxue therapy on patients with type 2 diabetes peripheral neuropathy has a good efficacy, can improve the neuropathy and vascular endothelial damage, improve related factors, and it was worthy clinical application.

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.

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.

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.

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.

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.

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.