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.

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.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment 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.

Advances in cardiovascular-related biomarkers to predict diabetic peripheral neuropathy

Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety.Notably,more than half of patients with DPN can be asymptomatic,which tends to delay early detection.Furthermore,the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration,gangrene and nontraumatic amputation,which decreases quality of life.Thus,it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention.It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes.The pathogenesis of both disorders involves vascular endothelial dysfunction.Emerging evidence indicates that traditional and novel cardiovascularrelated biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction.Additionally,beyond traditional cardiovascular-related biomarkers,novel cardiovascular-related biomarkers have been linked to diabetes and its complications.In this review,we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN,such as cardiac troponin T,B-type natriuretic peptide,Creactive protein,myeloperoxidase,and homocysteine,and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.

Peripheral Neuropathy and Associated Factors in Diabetics at the CNHU-HKM of Cotonou in 2021

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. The main objective of the study was to determine the prevalence of diabetic peripheral neuropathy and associated factors in diabetics in the University Clinic of Endocrinology Metabolism Nutrition of the CNHU-HKM, Cotonou, Benin 2021. This was a cross-sectional, analytical study that ran from 23 September to 23 December 2021. Admitted diabetic patients seen in consultation during the study period were included. The DN4 tool was used as the basis for data collection. Data analysis was performed using R software version 3.6.1. Multivariate analysis was used to identify factors associated with DPN. Out of 155 diabetics, 54 patients had diabetic peripheral neuropathy, a prevalence of 34.8%. The average age of our patients was 56.8 years and 56.8% were female. Of the patients, 54.7% had unbalanced diabetes. An association between DPN and gender (p = 0.022), occupation (p = 0.004), education (p = 0.011), hypertension (p = 0.017), smoking (p = 0.031), diabetic imbalance (p = 0.001), diabetic retinopathy (p = 0.020) and dyslipidaemia (p = 0.015) was observed. DPN was also associated with erectile dysfunction in men (p = 0.001). Conclusion: Diabetic peripheral neuropathy is common (34.8). Its occurrence is indicative of the presence of associated factors.

Diabetic neuropathy results in vasomotor dysfunction of medium sized peripheral arteries

BACKGROUND The effect of the sympathetic nervous system on peripheral arteries causes vasoconstriction when smooth muscle cells in the walls of blood vessels contract,which leads to narrowing of arteries and reduction of the blood flow.AIM To compare sympathetic vasomotor activation of the brachial arteries in healthy subjects and patients with painful diabetic neuropathy;and therefore,to assess whether there is significant vasomotor dysfunction of medium sized arteries in diabetic neuropathy.METHODS The study included 41 diabetic neuropathy patients and 41 healthy controls.Baseline diameter and flow rate of the brachial arteries were measured.Then,using a bipolar stimulus electrode,a 10 mA,1 Hz electrical stimulus was administered to the median nerve at the wrist level for 5 s.The brachial artery diameter and blood flow rate were re-measured after stimulation.RESULTS In the control group,the median flow rate was 70.0 mL/min prior to stimulation and 35.0 mL/min after stimulation,with a statistically significant decrease(P<0.001),which is consistent with sympathetic nervous system functioning(vasoconstriction).In the diabetic neuropathy group,median flow rate before the stimulation was 35.0 mL/min.After stimulation,the median flow rate was 77.0 mL/min;thus,no significant decrease in the flow rate was detected.In the control group,the median brachial artery diameter,which was 3.6 mm prior to stimulation,decreased to 3.4 mm after stimulation,and this decrease was also statistically significant(P=0.046).In the diabetic neuropathy group,the median brachial artery diameter increased from 3.4 mm to 3.6 mm following nerve stimulation.Once again,no narrowing was observed.CONCLUSION Our research suggests that diabetic neuropathy results in significant vasomotor dysfunction of medium sized peripheral arteries.Physiological vasoconstriction in response to sympathetic activation is impaired in diabetic neuropathy.

The active mechanism of the Sheng Yang San Huo decoction on diabetic peripheral neuropathy on network pharmacology

Objectives:To discuss the mechanism of Sheng Yang San Huo decoction on diabetic peripheral neuropathy using the network pharmacology method.Methods:The BATMAN-TCM database,TCM-ID database,Chinese Natural Product Chemical Composition Database,and TCMIP database were employed to screen the chemical active ingredients of each herb in Sheng Yang San Huo decoction based on the“Libinsky Drug Rules”.SwissTargetPrediction was used to screen effective action targets for each herb in the prescription.Additionally,Cytoscape 3.7.0 was utilized to construct a“drug-target”network.GeneCards,OMIM,and MaLaCards databases were utilized to gather targets related to diabetic peripheral neuropathy.VENNY 2.1 online platform was employed to match drug and disease targets,draw a Venn diagram,and construct a“drug-active compounds-common target”network using Cytoscape 3.7.0.gene ontology biological process analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the targets were conducted using the DAVID 6.8 database.Enrichment analysis results were visualized using the OmicShareTool online platform.Molecular docking was performed using CB-Dock2.Results:Following screening,a total of 217 active compounds and 132 potential targets were identified in Sheng Yang San Huo decoction.The effects are primarily enriched in pathways such as Lipid and Atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,and the IL-17 signaling pathway.The binding energy of the key active ingredients to the core protein targets of DPN was favorable.Conclusion:The study reveals the characteristics of multiple targets and pathways of Sheng Yang San Huo decoction,providing new insights for the clinical application of this prescription.

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.

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.

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 butyphthalide combined with antioxidant therapy on neurotrophic status and cellular oxidative damage in patients with cerebral infarction complicated by diabetic peripheral neuropathy

Objective:To study the effects of butyphthalide combined with antioxidant therapy on neurotrophic status and cellular oxidative damage in patients with cerebral infarction complicated by diabetic peripheral neuropathy.Methods: The patients with cerebral infarction complicated by diabetic peripheral neuropathy admitted to our hospital between January 2017 and December 2017 were selected and randomly divided into the control group receiving conventional therapy and the observation group receiving butyphthalide combined with antioxidant therapy. The contents of cytokines and oxidative damage markers in serum were measured before treatment and 4 weeks after treatment.Results: Serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I), vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF) and total antioxidant capacity (T-AOC) levels of both groups significantly increased whereas macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), chemokine ligand 16 (CXCL16), activated leukocyte cell adhesion molecule (ALCAM), platelet endothelial cell adhesion molecule-1 (PECAM-1), malondialdehyde (MDA), 8-iso-prostaglandin F2 (8-iso-PGF2 ) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels significantly decreased after treatment, and serum BDNF, IGF-I, VEGF, PD-ECGF and T-AOC levels of the observation group after treatment were significantly higher than those of the control group whereas MIF, TNF-α, CXCL16, ALCAM, PECAM-1, MDA, 8-iso-PGF2 and 8-OHdG levels were significantly lower than those of the control group.Conclusion: Butyphthalide combined with antioxidant treatment of cerebral infarction complicated by diabetic peripheral neuropathy can improve the neurotrophic status and alleviate the cellular oxidative damage.

Unique Traditional Chinese Medicine Therapy for Painful Diabetic Peripheral Neuropathy

Painful diabetic peripheral neuropathy is one of the common chronic complications of diabetes."Pain"is the most typical symptom in patients,which seriously affects their quality of life.Traditional Chinese medicine(TCM)treatment of the disease includes oral administration of Chinese medicine,TCM fumigation and acupuncture,etc.,which can significantly reduce the pain of patients and reduce the frequency of disease.Chinese decoctions regulate the imbalance of yin and yang in the human body through syndrome differentiation,so as to achieve the balance of yin and yang,which will then eliminate the disease.Chinese medicine fumigation make the medicine seep into the body from the skin to exert the medical effects,and nourish and dredge the meridians.There is no pain if the meridians are smooth flowing,there will be pain if the meridians are blocked,fumigation can be used alone or assisted by other treatment methods to enhance the efficacy.The characteristics of acupuncture are rapid painrelief,economic and convenient,and can quickly relieve pain for patients with low tolerance.

Effect of ultrashort wave therapy combined with antioxidant and neurotrophy therapy on nerve conduction function and serum cytokines in patients with diabetic peripheral neuropathy

Objective: To study the effect of ultrashort wave therapy combined with antioxidant and neurotrophy therapy on nerve conduction function and serum cytokines in patients with diabetic peripheral neuropathy. Methods: A total of 128 patients who were diagnosed with DPN in South District of Guang'anmen Hospital of China Academy of Chinese Medical Sciences between May 2014 and February 2017 were selected as the research subjects and randomly divided into electrotherapy + drug group and routine drug group;the nerve conduction velocity as well as serum levels of nerve cytokines and inflammatory cytokines were measured before treatment and 8 weeks after treatment. Results: Median nerve and common peroneal nerve MNCV, median nerve and superficial peroneal nerve SNCV as well as serum CNTF, BDNF, SDF-1α, IGF-1, CAT and HO-1 levels of both groups 8 weeks after treatment were significantly higher than those before treatment while serum ICAM-1, TNF-α, IL-6, ET-1, MDA and 8-OHdG levels were significantly lower than those before treatment;median nerve and common peroneal nerve MNCV, median nerve and superficial peroneal nerve SNCV as well as serum CNTF, BDNF, SDF-1α, IGF-1, CAT and HO-1 levels of electrotherapy + drug group 8 weeks after treatment were significantly higher than those of routine drug group while serum ICAM-1, TNF-α, IL-6, ET-1, MDA and 8-OHdG levels were significantly lower than those of routine drug group. Conclusion: Ultrashort wave therapy combined with antioxidant and neurotrophy therapy for DPN can improve the nerve conduction function and neurotrophic state, and also inhibit the inflammatory response and oxidative stress response.

Treatment of Peripheral Neuropathy: Combination Therapy Using LED Light, Extracorporeal Shockwave Therapy, Platelet Rich Plasma, and an Oral Dietary Supplement

Objectives: Peripheral neuropathy (PN) is a significant contributor to disability in the elderly. It is also one of the most prevalent complications of type 2 diabetes, prediabetes and metabolic syndrome. PN is commonly associated with pain, numbness, tingling, burning, and cramping in the feet and legs. Current treatment options are limited to controlling pain, seizures and use of antidepressant medications. These treatments have undesirable side effects and don’t stop PN progression. Here we utilized a combination of individual-specific modalities to improve local circulation and relieve PN symptoms. Methods: We conducted an open-label, multicenter pilot trial with 34 subjects (19 males and 15 females ranging from 40 - 85 years of age). All of the participants were diagnosed with peripheral neuropathy and had bilateral symptoms in their feet, and many reported the same symptoms (pain, numbness, tingling, burning, and cramping) in their lower legs. The duration of symptoms ranged from four months to over six years. On Day 0, subjects were given a 90-day supply of the oral supplement with dosing instructions and a LED light therapy device. They also received three platelet-rich plasma (PRP) injections in their lower extremities. Subjects also received an extracorporeal shockwave therapy (ESWT) treatment for each foot and subsequently twice per week for the first six weeks, then once weekly for the duration of the study. Subjects filled out the Brief Pain Index (BPI) at weekly intervals. On Day 90, subjects completed the Patient Global Impression of Change (PGIC) survey. Results: There were significant responses to pain, as evidenced by BPI scores at weeks 8, 9, 10 and 11 (p = 0.02, 0.01, 0.02, and 0.003, respectively). Analysis of the final day PGIC survey showed a favorable outcome for 73% of participants (p = 0.003), with the majority reporting Very Much Improved. Conclusions: By utilizing a multi-modality treatment protocol that includes PRP, LED light therapy, ESWT and an oral dietary supplement, we observed significant reductions in BPI scores. Quality of life and their overall impression of change (PGIC) were significantly improved, and there were no significant side effects.

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.