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.

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.

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.

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.

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.

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.

Balance training in the intervention of fall risk in elderly with diabetic peripheral neuropathy: A review

Diabetic peripheral neuropathy(DPN)was the most common complications of elderly diabetic,which could contribute to an increased risk of falling.Despite the increased prevalence of elderly diabetic,high risk of falls and serious consequences of falls in elderly with DPN,It is necessary to adopt means of reducing the risk of falls in elderly with DPN.Impaired balance in the elderly with DPN was the most important risk factor of increasing falls.This review will introduce the epidemiology of falls in elderly with DPN,analysis the reasons for high risk of falls in elderly with DPN,provide a review of the development of balance training in the intervention of fall risk in elderly with DPN and offer recommendations to medical personnels on how to provide an efficient balance training for elderly with DPN.

Prostaglandin E_1 in conjunction with high doses of vitamin B_(12) improves nerve conduction velocity of patients with diabetic peripheral neuropathy

BACKGROUND： Prostaglandin El improves diabetic peripheral neuropathy in symptoms and sensory threshold. Vitamin Bi and methyl-vitamin BI2 improve microcirculation to peripheral nerve tissue and promote neurotrophy. OBJECTIVE： To observe motor nerve and sensory nerve conduction velocity in patients with diabetic peripheral neuropathy, prior to and after treatment with prostaglandin El, vitamin B I and different doses of vitamin B 12. DESIGN, TIME AND SETTING： Randomized, controlled experiment, performed at the Department of Neurology, Beijing Hantian Central Hospital, between February 2002 and September 2007. PARTICIPANTS： A total of 122 patients with type 2 diabetic peripheral neuropathy; 73 males and 49 females were included. All patients met the diagnostic criteria of diabetes mellitus, as determined by the World Health Organization in 1999 and 2006, and also the diagnostic criteria of diabetic peripheral neuropathy. For each subject, conduction disorders in the median nerve and in the common peroneal nerve were observed using electromyogram. Also, after diet and drug treatment, the blood glucose level of subjects was observed to be at a satisfactory level for more than two weeks, and the symptoms of diabetic peripheral neuropathy were not alleviated. METHODS： All patients were randomly divided into the following three groups. A control group （n = 40）, in which, 100 mg vitamin B1 and 500 μg vitamin BI2 were intramuscularly injected. A vitamin B12 low-dose treated group （ n = 42）, in which 10 μ g prostaglandin E1 in 250 mL physiological saline was intravenously injected once a day and 100 mg vitamin BI and 500 11 g vitamin BI2 was intramuscularly injected once a day. Lastly, a vitamin B12 high-dose treated group （n = 40）, in which administration was the same as in the vitamin B12 low-dose treated group, except that 500 11 g vitamin BI2 was replaced by 1mg vitamin B12. Administration was performed for four weeks for each group. MAIN OUTCOME MEASURES： The motor nerve and sensory nerve conduction velocity of the median nerve and the common peroneal nerve were determined using an electromyogram electronic stimulator （Neuropack-11, Nihon Kohden, Japan）. RESULTS： The motor nerve and sensory nerve conduction velocities of the median nerve and the common peroneal nerve were significantly faster after treatment compared to before treatment in all 3 groups （P 〈 0.05q）.01）. Compared with the control group, the motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 low-dose treated group and in the vitamin B12 high-dose treated group （P 〈 0.01）. The motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 high-dose treated group compared to the vitamin B12 low-dose treated group （P 〈 0.05）. CONCLUSION： Prostaglandin E1, in conjunction with vitamin B12, can improve neural functional states and speed up peripheral motor nerve and sensory nerve conduction velocity in diabetic peripheral neuropathy. In addition, better effects are achieved using prostaglandin E1 in conjunction with high doses of vitamin B 12.

Effect of Large Dose Methylcobalamin on Diabetic Peripheral Neuropathy

The effects of large dose methylcobalamin injection on diabetic peripheral neuropathy in patients were observed to observe the subjective symptom of diabetic perpheral neuropathy （DPN） patients and detect the motor nerve conduction velocity （MCV） and sense nerve conduction velocity （SCV）. Fifteen patients were received large dose methylcobalamin injection for two weeks as treatment group, another eleven patients were received muscular injection VitB1 100mg/ d, VitB12 500ug/ d for two weeks as control group. After 2 weeks treatment the subjective symptoms and signs were significantly improved with a total effective rate of 82.9% in the treatment group however the effective rate only has 52.0% in the control group. The result has obvious difference in statistics nerve MCV in median common peroneal nerve, SCV in median and superficial peroneal nerve were improved significantly in the treatment group and no such changes were observed in the control group. So, large dose methylcobalamin is an effective and safe agent for treatment of diabetic peripheral neuropathy.

Association between serum Sestrin2 level and diabetic peripheral neuropathy in type 2 diabetic patients

BACKGROUND Diabetic peripheral neuropathy(DPN)is a chronic and serious microvascular complication of diabetes linked to redox imbalance.Sestrin2,a novel inducible stress protein,participates in glucose metabolic regulation and redox homeostasis.However,the association between serum Sestrin2 and DPN is unknown.AIM To explore the association between serum Sestrin2 and DPN in patients with type 2 diabetes mellitus(T2DM).METHODS A total of 96 T2DM patients and 39 healthy volunteers,matched by age and sex,participated in this cross-sectional study.Clinical features and metabolic indices were identified.Serum Sestrin2 was measured by ELISA.The association between Sestrin2 and DPN was studied.Correlation and logistic regression analyses were used to evaluate the associations of different metabolic indices with Sestrin2 and DPN.RESULTS The 96 patients with T2DM were divided into DPN(n=47)and patients without DPN(n=49).Serum Sestrin2 was significantly lower in healthy volunteers than in all T2DM patients combined[9.10(5.41-13.53)ng/mL vs 12.75(7.44-23.80)ng/mL,P<0.01].T2DM patients without DPN also had significantly higher levels of Sestrin2 than healthy volunteers[14.58(7.93-26.62)ng/mL vs 9.10(5.41-13.53)ng/mL,P<0.01].However,T2DM patients with DPN had lower circulating Sestrin2 levels compared to T2DM patients without DPN[9.86(6.72-21.71)ng/mL vs 14.58(7.93-26.62)ng/mL,respectively,P<0.01].Bivariate correlation analysis revealed that serum Sestrin2 was positively correlated with body mass index(r=0.672,P=0.000),hemoglobin A1c(HbA1c)(r=0.292,P=0.000),serum creatinine(r=0.206,P=0.016),triglycerides(r=0.731,P=0.000),and fasting glucose(r=0.202,P=0.040),and negatively associated with estimated glomerular filtration rate(r=-0.230,P=0.007).After adjustment for sex,age,HbA1c,and diabetes duration,multiple regression analysis revealed that Sestrin2 was independently correlated with body mass index and triglyceride levels(P=0.000).Logistic regression analyses indicated that Sestrin2,diabetes duration,and high-density lipoprotein were strongly associated with DPN(odds ratio=0.855,1.411,and 0.041,respectively).CONCLUSION Our results show Sestrin2 is decreased in T2DM patients with DNP.As lower Sestrin2 is independently associated with DPN,Sestrin2 may contribute to progression of DPN in T2DM patients.

Effect of mild moxibustion in improving the quality of life of patients with diabetic peripheral neuropathy

Objective:The objective of this study is to investigate the effect of mild moxibustion on quality of life of patients with type 2 diabetic peripheral neuropathy(DPN).Materials and Methods:Fifty‑five patients with type 2 DPN from October 2018 to July 2019 were recruited in the present study and randomly divided into two groups:27 cases in the control group and 28 cases in the intervention group.The control group received routine treatment of hypoglycemic,hypotensive,mecobalamin nutritional nerve,while the intervention group received mild moxibustion on the basis of the control group.The course of treatment for both groups was 10 weeks.The quality of life of the two groups was assessed using short form‑36 health survey and compared with t‑test at 0.05 significance level.Results:The total score of the short form‑36 in the intervention group was higher than the control group(P<0.05);the scores of bodily pain,physical functioning(PF),general health(GH),and mental health dimensions in the intervention group increased significantly compared with the control group(P<0.05);the scores of role physical,social functioning(SF),vitality,and role‑emotional(RE)dimensions showed no between‑group difference(P>0.05).Conclusion:Mild moxibustion can effectively improve the quality of life of patients with type 2 DPN,relieve patient pain symptoms,and improve PF and GH.

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.

Effector mechanism of Yunnan medicine “Yiqi Tongluo soup” in alleviating diabetic peripheral neuropathy by promoting autophagy

Objective:This study aimed to evaluate the effector mechanism of Yiqi Tongluo soup in alleviating diabetic peripheral neuropathy.Methods:Thirty male SD rats were divided into the control group,mode1 group,and Yiqi Tongluo group.Each group consists of 10 rats.Except for the normal group,a high-sugar and high-fat diet combined with streptozocin injection were administered to the groups to constnuct the type 2 diabetes mellitus model.Then,6.48 g/kg of Yiqi Tongluo soup was administered to the Yiqi Tongluo group every day by gavage.An equal volume of physiological saline was administered to the control and model groups every day by gavage.During the experiment,changes in blood glucose and nerve conduction velocity were monitored in all groups.After the experiment,hematoxylin and eosin and luxol fast blue staining were carried out,and morphological changes in the sciatic nerve and myelin sheath in all groups were observed.Western blot was used to observe changes in expression levels of autophagy related proteins,Beclin-1,LC3,and P62.Results:Blood glucose significantly increased,and nerve conduction velocity significantly decreased in the model group.Yiqi Tongluo soup significantly decreased blood glucose level while simultaneously increasing nerve conduction velocity.Hematoxylin and eosin and luxol fast blue myelin sheath staining results showed that Yiqi Tongluo soup could improve sciatic nerve disorder,irregular myelin sheath morphology,and demyelination in type 2 diabetes mellitus rats.Western blot results showed that Beclin-1 and LC3I/LC3I expression levels in the model group significantly decreased,while P62 level significantly increased.Compared with the model group,Beclin-1 and LC3II/LC3I expression levels significantly increased and P62 levels significantly decreased in the Yiqi Tongluo group.Conclusion:Yiqi Tongluo soup can inhibit diabetic peripheral neuropathy by increasing autophagy.

Efficacy evaluation of high-frequency ultrasound in the treatment of diabetic peripheral neuropathy with α-lipoic acid combined with traditional Chinese medicine package treatment

Objective:To use high-frequency ultrasound to evaluate the efficacy ofα-lipoic acid combined with traditional Chinese medicine in the treatment of diabetic peripheral neuropathy(DPN),so as to provide a basis for clinical medication and evaluation of therapeutic effect.Methods:From December 2018 to December 2019,110 patients with DPN who met the inclusion and exclusion criteria were divided into observation group and control group according to different treatment plans.The control group was treated withα-lipoic acid,and the observation group was treated withα-lipoic acid combined with traditional Chinese medicine encapsulation treatment,and used high-frequency ultrasound,nerve conduction velocity and serological examination to comprehensively evaluate the effectiveness of the two treatment methods.Results:The mean amplitude of glycemic excursions(MAGE)value of the observation group and the control group after treatment was significantly lower than before treatment(P<0.05);After treatment,the SCV of the ulnar nerve,median nerve,and common peroneal nerve in the two groups was significantly faster than before treatment(P<0.05).Similar to SCV,the MCV of the three nerves measured after treatment in the two groups was significantly faster than before treatment(P<0.05).Compared between the groups after treatment,the three kinds of nerve SCV and MCV in the observation group were significantly faster than those in the control group(P<0.05).The cross-sectional area(CSA)value of the ulnar nerve,median nerve and common peroneal nerve in the observation group after treatment was significantly lower than before treatment(P<0.05).Compared with the control group after treatment,the three nerves CSA in the observation group was significantly lower than that in the control group(P<0.05).Abnormal ultrasound performance:The proportion of abnormal ultrasound performances of the ulnar nerve,median nerve,and common peroneal nerve in the observation group after treatment was significantly lower than before treatment(P<0.05).The composition ratio of internal echo reduction and ambiguity in the observation group after three nerve treatments was significantly lower than that in the control group after treatment(P<0.05).In the correlation analysis,the three kinds of nerve CSA before and after treatment were negatively correlated with SCV and amplitude(P<0.05),and positively correlated with latency(P<0.05).Conclusion:The combination ofα-lipoic acid and Chinese medicine encapsulation technology has a good effect on the treatment and repair of DPN nerve damage,and can be routinely applied in clinical treatment.High-frequency ultrasound can intuitively observe changes in peripheral nerves and can be used to evaluate the prognosis of DPN.

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.