Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-k...Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-kappa B(NF-κB)pathway contributes to inflammation-induced peripheral nerve damage,affecting cell survival.Juan Bi Tong Luo(JBTL),a traditional Chinese medicine(TCM),has demonstrated favorable results in alleviating pain and numbness in patients with DPN;however,whether JBTL exerts its effect through the MAPK mediating NF-κB pathway remains unclear.Methods:This study investigated whether JBTL modulates apoptosis in DPN models and Schwann cells cultured in 100 mM of glucose by MAPK/NF-κB.Results:The JBTL altered inflammation,reduced peripheral nerve tissue damage,and improved cell survival rates by down-regulating MAPK/NF-κB.Conclusion:Our findings demonstrate that the effect of JBTL on DPN is likely mediated by suppressing inflammation induced by the MAPK/NF-κB pathway,thus providing evidence for the clinical efficacy of JBTL in treating DPN.展开更多
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 dia...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.展开更多
Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic ...Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.展开更多
Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retin...Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.展开更多
Introduction: Diabetic neuropathy is one of the most common chronic complications of diabetes. Most of the studies on the subject in the sub region, particularly in Burkina Faso, dealt it with the study of the complic...Introduction: Diabetic neuropathy is one of the most common chronic complications of diabetes. Most of the studies on the subject in the sub region, particularly in Burkina Faso, dealt it with the study of the complications of diabetes, or one of its components. Our study was designed to study in particular in all its aspects, by searching for its peculiarities in our context, for improvement of its support. Methodology: This is a cross-sectional descriptive study carried out in 150 diabetic patients aged at least 15 years followed in the Department of Internal Medicine at Yalgado Ouedraogo University Teaching Hospital. All patients included had agreed to participate in our survey after informed consent. We collected the data during the period from 2015 November to 2016 June. Each patient was evaluated by the DN4 questionnaire and clinically by a neurological examination. We determinated the frequency, the sociodemographic, clinical and therapeutic characteristics of diabetes neuropathy and its related factors. Results: The frequency of diabetic neuropathy was 80.7%. Peripheral neuropathies were seen in 81.8% of cases and autonomic neuropathies in 72.7% of cases. Autonomic neuropathy was dominated by the DAN (59.1%), and erectile dysfunction (44%). There was a high comorbidity with physical inactivity (66.9%), obesity (49.4%) and hypertension (38.8%). There were poorly controlled patients in 38.8%. A link was found between T2DM and neuropathy (p = 0.014). Painful diabetes was related to the quality of glycemic control (p = 0.007), and hypertension (p = 0.021). A link was also found between tobacco consumption (p < 0.001), male (p < 0.001), and urogenital autonomic neuropathy. Conclusion: Diabetic neuropathies are very common in our context and could be a haunting to the practitioner with the progression of diabetes and its corollary of degenerative complications. There was a significant association between Type 2 Diabetes mellitus and the presence of peripheral diabetic neuropathy.展开更多
Diabetic gastrointestinal autonomic neuropathy(DGAN)is a common and debilitating complication of diabetes,characterized by autonomic dysfunction in the gastrointestinal system.The complex pathophysiology of DGAN invol...Diabetic gastrointestinal autonomic neuropathy(DGAN)is a common and debilitating complication of diabetes,characterized by autonomic dysfunction in the gastrointestinal system.The complex pathophysiology of DGAN involves neuronal injury that is intrinsically linked to gut dysbiosis.Multiple factors,including hyperglycemia,oxidative stress,and inflammation,significantly contribute to neuronal damage,manifesting as symptoms such as delayed gastric emptying,diarrhea,and constipation.Recent studies have demonstrated that patients with diabetes experience substantial alterations in gut microbiota composition,potentially exacerbating gastrointestinal symptoms.Microbial metabolites may modulate neurotransmitter synthesis and release,directly affecting autonomic nerve function,while dysbiosis amplifies oxidative stress and inflammation,further compromising the enteric nervous system and worsening DGAN.Advances in multi-omics technologies now provide deeper insights into molecular mechanisms of DGAN and its interactions with microbiota.Early diagnosis leveraging biomarkers,gut microbiota analysis,and advanced imaging promises more effective interventions.Emerging therapeutic strategies targeting oxidative stress,inflammation,and gut microbiota represent promising approaches for managing DGAN.Future research should focus on large-scale,multi-ethnic studies and therapies targeting specific microbial metabolites to refine diagnosis and treatment approaches.展开更多
Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent researc...Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent research highlights therole of epigenetic markers including DNA methylation, histone modifications,and non-coding RNAs in regulating inflammatory responses, neuronal degeneration,and tissue repair. This review explores the epigenetics of DN and DFUs,emphasizing key regulatory pathways that influence disease progression andwound healing outcomes. Genome-wide DNA methylation studies reveal acceleratedepigenetic aging and metabolic memory effects in DN, contributing tosensory neuron dysfunction and neuropathic pain. Epigenetic dysregulation ofinflammatory mediators such as Toll-like receptors and the Nod-like receptorfamily, pyrin domain-containing 3 inflammasome further exacerbates neuronaldamage and delays wound healing. Additionally, histone deacetylases play apivotal role in oxidative stress regulation via the Nrf2 pathway, which is critical for both neuronal protection and angiogenesis in DFUs. Non-coding RNAs, particularly microRNAs (miRNAs),long non-coding RNAs (lncRNAs), and circular RNAs, are emerging as central regulators of the epigeneticcrosstalk between DN and DFUs. Several miRNAs, including miR-146a-5p and miR-518d-3p, are implicated inneuropathy severity, while lncRNAs such as nuclear enriched abundant transcript 1 modulate angiogenesis andwound repair. Cellular reprogramming of DFU fibroblasts has also been shown to induce pro-healing miRNAsignatures, offering potential therapeutic avenues. Furthermore, recent whole-genome and transcriptomic analysesof DFU-derived monocytes and Charcot foot lesions reveal unique epigenetic signatures that may serve as biomarkersfor early detection and personalized interventions. This epigenetic interplay between DN and DFUpathogenesis not only enhances our knowledge of disease mechanisms but also opens avenues for targetedepigenetic therapies to improve clinical outcomes.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is the most prevalent complication of type 2 diabetes mellitus(T2DM).Due to a lack of specific biomarkers,the early diagnosis of this disorder is limited.AIM To identify a...BACKGROUND Diabetic peripheral neuropathy(DPN)is the most prevalent complication of type 2 diabetes mellitus(T2DM).Due to a lack of specific biomarkers,the early diagnosis of this disorder is limited.AIM To identify and validate serum amino acids that could discriminate T2DM patients with DPN from those without DPN.METHODS T2DM patients with DPN,T2DM patients without DPN,and healthy controls were recruited for this study.The participants comprised two nonoverlapping cohorts:A training cohort(DPN=84 participants,T2DM=82 participants,normal=50 participants)and a validation cohort(DPN=112 participants,T2DM=93 participants,normal=58 participants).A prediction model of the ability of serum amino acids to distinguish DPN from T2DM was established using a logistic regression model,and area under the curve(AUC)analysis was used to evaluate the diagnostic ability of the model.In addition,the serum amino acid levels of 13 DPN patients were also detected before treatment and after 3 months of treatment.RESULTS A clinical detection method for the diagnosis of DPN based on a biomarker panel of three serum amino acids and diabetes duration was developed.The diagnostic model demonstrated AUC values of 0.805(95%CI:0.739-0.871)and 0.810(95%CI:0.750-0.870)in the training and verification cohorts,respectively.In the identification of T2DM patients and normal controls,the AUC values were 0.891(95%CI:0.836-0.945)and 0.883(95%CI:0.832-0.934)in the training and validation cohorts,respectively.Arginine and tyrosine levels were increased after treatment,whereas aspartic acid levels were decreased after treatment.CONCLUSION This study successfully identified and validated the metabolomic significance of arginine,tyrosine,and glutamic acid as potential biomarkers for diagnosing DPN.These findings are particularly valuable,as they establish a foundational step toward developing the first routine laboratory test for DPN.Moreover,the diagnostic model that was constructed in this study effectively distinguishes DPN patients from those with T2DM without neuropathy,thereby potentially facilitating early diagnosis and intervention.展开更多
BACKGROUND Diabetic neuropathy(DN)is a progressive disorder with limited effective treatment options.AIM To identify potential therapeutic targets for DN by integrating plasma proteomic and transcriptomic data.METHODS...BACKGROUND Diabetic neuropathy(DN)is a progressive disorder with limited effective treatment options.AIM To identify potential therapeutic targets for DN by integrating plasma proteomic and transcriptomic data.METHODS A comprehensive analytical framework was developed to identify multi-omics biomarkers of DN.Protein-protein interaction network and Gene Ontology analyses were performed to explore the biological functions of biomarkers.Tier 1 target proteins were further analyzed.Candidate drug prediction and molecular docking studies were conducted to identify potential treatments while assessing the side effects of key target proteins.The mediation of immune cells in the association between proteins and DN was examined through two-step network Mendelian randomization(MR)analysis.RESULTS Nine DN-associated proteins were identified by analyzing protein quantitative trait loci from extensive genome-wide association study data.BTN3A1 and MICB were confirmed using MR,summary data-based MR,and colocalization analyses.Of the nine,HSPA1B,PSMB9,BTN3A1,SCGN,NOTUM,and MICB showed negative associations with DN,whereas WARS,BRD2,and CSNK2B were positive.Gene Ontology analysis indicated enrichment in inflammatory response and neuronal injury pathways.BTN3A1 and MICB were identified as Tier 1 targets.Drug prediction and molecular docking analyses indicated cyclosporin A as a potential therapeutic candidate.Two-step network MR analysis showed that MICB mediated DN through human leukocyte antigen-DR++monocytes.These integrated findings point to an immune-mediated mechanism with translational potential and nominate BTN3A1 and MICB for focused functional validation.CONCLUSION Our integrated multi-omics approach identified two promising therapeutic targets for DN,laying the groundwork for new treatment strategies and enhancing our understanding of MICB’s role in DN.展开更多
Objective:Diabetic Peripheral Neuropathy(DPN)is a common chronic complication of diabetes that currently has no therapeutic recourse.Advanced DPN stages are characterized by severe symptoms that place a huge burden on...Objective:Diabetic Peripheral Neuropathy(DPN)is a common chronic complication of diabetes that currently has no therapeutic recourse.Advanced DPN stages are characterized by severe symptoms that place a huge burden on patients and healthcare systems.To the best of our knowledge,research hotspots within the field of DPN are yet to be visually analyzed,and so is the exploration of developmental dynamics within the same discipline.Methods:Herein,DPN articles published between 2002 and 2022 were retrieved from the Web of Science Core Collection database.Following that,bibliometric analysis was performed on these articles using CiteSpace,VOSviewer,Microsoft Excel,and R-bibliometrix tools.Results:We retrieved 2,761 DPN articles involving 11,605 researchers from 1,140 institutions in 99 countries/regions.The United States was the country/region with the highest number of publications.The most productive author was Malik Rayaz A from the University of Manchester,which was the most productive institution.The most co-cited journals were Diabetes Care,Pain,and Neurology.On the other hand,#0 neuropathic pain,#1 neuropathic pain treatment and#2 peripheral neuropathy were the most clustered keywords in co-cited references.Based on the clustering of keywords,timeline graphs,and citation bursts,“risk”,“corneal confocal microscopy”and“systematic review”were identifi ed as the key issues for future DPN research.Conclusion:This article summarizes the current DPN research status and focus areas,reveals the future development trend,and points out potential research directions for DPN scholars.展开更多
Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficienc...Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.展开更多
Background:Diabetic retinal neuropathy(DRN)leads to significant visual impairment;however,no existing animal model fully replicates its neural alterations,and inconsistent induction protocols with high mortality rates...Background:Diabetic retinal neuropathy(DRN)leads to significant visual impairment;however,no existing animal model fully replicates its neural alterations,and inconsistent induction protocols with high mortality rates hinder long-term investigations.Methods:Adult male rabbits were randomly assigned to four experimental groups,each receiving a single intravenous injection of varying doses of alloxan and one control group.The safety and efficacy of alloxan in inducing diabetes were evaluated to determine the optimal dose.At 9 weeks following injection with alloxan,retinal function was assessed using full-field electroretinography(ERG)and visual evoked potentials(VEPs).Retinal structure was examined in rabbits using spectral-domain optical coherence tomography(SD-OCT),Optos ultra-widefield(Optos UWF)false-color imaging,and widefield fundus fluorescein angiography(WF-FFA).Results:Rabbits in the 80 mg/kg alloxan group exhibited fewer complications,lower mortality,and a higher model success rate compared to other groups.At 9 weeks post-injection,these rabbits demonstrated significantly elevated hemoglobin A1c and total cholesterol(p<0.05)relative to controls.ERG revealed statistically significant reductions in oscillatory potential and b-wave amplitudes(p<0.05),while VEP indicated decreased P2 amplitude(p<0.001)and prolonged P2 latency(p<0.05).SD-OCT,Optos UWF imaging,and WF-FFA demonstrated no significant changes in vascular abnormalities.Additionally,Hematoxylin and Eosin staining revealed retinal swelling(p<0.05),and immunofluorescence confirmed glial activation and neuronal loss.Conclusions:A single intravenous injection of 80 mg/kg alloxan effectively and safely induced DRN in rabbits,resulting in neural retina damage,thereby establishing this model as an ideal model for DRN research.展开更多
Purpose:To explore the clinical value of Electromyography(EMG)and Heart Rate Variability(HRV)in the diagnosis of early DPN and provide the basis for early diagnosis,treatment,and prevention of DPN.Methods:105 patients...Purpose:To explore the clinical value of Electromyography(EMG)and Heart Rate Variability(HRV)in the diagnosis of early DPN and provide the basis for early diagnosis,treatment,and prevention of DPN.Methods:105 patients with type 2 diabetes mellitus(T2DM)in the Changji People’s Hospital were treated from January 2023 to December 2023.They were stratifi ed into DPN-symptomatic(DPN group,n=55)and DPN-asymptomatic(NDPN group,n=50)cohorts based on the presence or absence of clinically confi rmed diabetic peripheral neuropathy.The clinical biochemical indicators,nerve electromyography,and HRV parameters were obtained from electronic medical records,and diff erences in detection results were compared between the two groups.Logistic regression was applied to analyze the infl uencing factors of DPN in diabetes patients.The receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of EMG combined with other parameters for DPN.Results:From the results of the general information,diabetes duration,glycosylated hemoglobin(HbA1c),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)and FBG in the DPN group were significantly differences compared with the NDPN group(p<0.05).There were no statistically significant differences in gender,age years,uric acid,and other general data(p>0.05).Compared with the NDPN group,the motor nerve conduction velocity(MNCV),sensory nerve conduction velocity(SNCV)of the ulnar nerve,median nerve,and tibial nerve in the DPN group were statistically signifi cant(p>0.05).The DPN group had higher average F wave latency and H wave latency in the tested nerve,with statistical signifi cance(p<0.05).HRV parameters decreased signifi cantly(SDNN,rMSSD,PNN50,and SDANN,all p<0.05).ROC analysis showed that the area under the ROC curve(AUC)of the combined diagnosis of DPN by duration of diabetes,HbA1c,EMG,and HRV was 0.897,the accuracy was 82.86%,the sensitivity was 78.00%,and the specifi city was 87.27%.The AUC of the combined diagnosis of the four parameters for DPN was signifi cantly higher than that of each alone(p<0.05).Conclusion:The combination of EMG and HRV has a high value in the assessment of DPN and can be used for early assessment of the extent of the lesion.展开更多
Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows pro...Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.展开更多
BACKGROUND The trend of risk prediction models for diabetic peripheral neuropathy(DPN)is increasing,but few studies focus on the quality of the model and its practical application.AIM To conduct a comprehensive system...BACKGROUND The trend of risk prediction models for diabetic peripheral neuropathy(DPN)is increasing,but few studies focus on the quality of the model and its practical application.AIM To conduct a comprehensive systematic review and rigorous evaluation of prediction models for DPN.METHODS A meticulous search was conducted in PubMed,EMBASE,Cochrane,CNKI,Wang Fang DATA,and VIP Database to identify studies published until October 2023.The included and excluded criteria were applied by the researchers to screen the literature.Two investigators independently extracted data and assessed the quality using a data extraction form and a bias risk assessment tool.Disagreements were resolved through consultation with a third investigator.Data from the included studies were extracted utilizing the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies.Additionally,the bias risk and applicability of the models were evaluated by the Prediction Model Risk of Bias Assessment Tool.RESULTS The systematic review included 14 studies with a total of 26 models.The area under the receiver operating characteristic curve of the 26 models was 0.629-0.938.All studies had high risks of bias,mainly due to participants,outcomes,and analysis.The most common predictors included glycated hemoglobin,age,duration of diabetes,lipid abnormalities,and fasting blood glucose.CONCLUSION The predictor model presented good differentiation,calibration,but there were significant methodological flaws and high risk of bias.Future studies should focus on improving the study design and study report,updating the model and verifying its adaptability and feasibility in clinical practice.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have...BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.展开更多
Diabetes mellitus(DM)and its complications continue to impose a substantial burden on healthcare systems worldwide.Diabetic neuropathy(DN)is one of the most common chronic microvascular and neurodegenerative complicat...Diabetes mellitus(DM)and its complications continue to impose a substantial burden on healthcare systems worldwide.Diabetic neuropathy(DN)is one of the most common chronic microvascular and neurodegenerative complications of DM.It is clinically characterized by allodynia,hyperalgesia,and abnormal or absent nerve fiber sensation,which collectively contribute to poor quality of life,sleep disturbances,depression,and increased mortality.Although several pharmacological agents are available to alleviate DN-related symptoms,their limited long-term efficacy and adverse side effects underscore the urgent need for novel therapeutic approaches.This limitation may be attributed to an incomplete understanding of the underlying mechanisms of DN.Accumulating evidence has highlighted the contribution of glial cells including astrocytes,microglia,and oligodendrocytes to the pathogenesis of DN.However,the specific role of astrocytes remains insufficiently defined.Therefore,this review provides a comprehensive evaluation of current knowledge regarding astrocyte involvement in DN mechanisms,with the goal of clarifying their contribution to disease progression and identifying potential therapeutic targets.展开更多
Diabetic peripheral neuropathy(DPN)is a common complication of diabetes and is characterized by sensory and motor impairments resulting from neural injury.Schwann cells(SCs),which are important for peripheral nerve fu...Diabetic peripheral neuropathy(DPN)is a common complication of diabetes and is characterized by sensory and motor impairments resulting from neural injury.Schwann cells(SCs),which are important for peripheral nerve function,are compromised under hyperglycemic conditions,leading to impaired axonal re-generation and demyelination.Autophagy,a cellular degradation process,is essential for SC function and significantly influences DPN progression.This article highlights the significance of autophagy in SCs and its potential as a pharmacotherapeutic target in DPN.We discuss the mechanisms of autophagy in SCs,including the mammalian target of rapamycin,adenosine monophosphate-activated protein kinase,and phosphatase and tensin homolog-induced putative kinase/parkin pathways,and their dysregulation in DPN.This article also exa-mines various natural products and chemical agents that modulate autophagy and enhance the efficacy of DPN treatment.These agents target key signaling pathways,such as adenosine monophosphate-activated protein kinase/mam-malian target of rapamycin and demonstrate potential in promoting nerve re-generation and restoring SC function.The roles of exosomes,long non-coding RNA,and proteins in the regulation of autophagy have also been explored.In conclusion,targeting autophagy in SCs is a promising strategy for DPN treatment and offers new insights into therapeutic interventions.Further research is war-ranted to fully exploit these targets for clinical applications.展开更多
基金funded by grants from the Suzhou Gusu Health Talents Project(grant No.GSWS2024050 to Liu W)Natural Science Foundation Project of Nanjing University of Chinese Medicine(grant No.XZR2021043 to Liu W and grant No.XZR2023021 to Huang F)+1 种基金Suzhou Science Education Health Youth Project(grant No.KJXW2021046 to Liu W)Suzhou Major Disease Multi-center Clinical Research Project(grant No.DZXYJ202410 to Huang F).
文摘Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-kappa B(NF-κB)pathway contributes to inflammation-induced peripheral nerve damage,affecting cell survival.Juan Bi Tong Luo(JBTL),a traditional Chinese medicine(TCM),has demonstrated favorable results in alleviating pain and numbness in patients with DPN;however,whether JBTL exerts its effect through the MAPK mediating NF-κB pathway remains unclear.Methods:This study investigated whether JBTL modulates apoptosis in DPN models and Schwann cells cultured in 100 mM of glucose by MAPK/NF-κB.Results:The JBTL altered inflammation,reduced peripheral nerve tissue damage,and improved cell survival rates by down-regulating MAPK/NF-κB.Conclusion:Our findings demonstrate that the effect of JBTL on DPN is likely mediated by suppressing inflammation induced by the MAPK/NF-κB pathway,thus providing evidence for the clinical efficacy of JBTL in treating DPN.
文摘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.
基金Supported by the King Salman Center for Disability Research,No.KSRG-2023-407.
文摘Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.
文摘Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.
文摘Introduction: Diabetic neuropathy is one of the most common chronic complications of diabetes. Most of the studies on the subject in the sub region, particularly in Burkina Faso, dealt it with the study of the complications of diabetes, or one of its components. Our study was designed to study in particular in all its aspects, by searching for its peculiarities in our context, for improvement of its support. Methodology: This is a cross-sectional descriptive study carried out in 150 diabetic patients aged at least 15 years followed in the Department of Internal Medicine at Yalgado Ouedraogo University Teaching Hospital. All patients included had agreed to participate in our survey after informed consent. We collected the data during the period from 2015 November to 2016 June. Each patient was evaluated by the DN4 questionnaire and clinically by a neurological examination. We determinated the frequency, the sociodemographic, clinical and therapeutic characteristics of diabetes neuropathy and its related factors. Results: The frequency of diabetic neuropathy was 80.7%. Peripheral neuropathies were seen in 81.8% of cases and autonomic neuropathies in 72.7% of cases. Autonomic neuropathy was dominated by the DAN (59.1%), and erectile dysfunction (44%). There was a high comorbidity with physical inactivity (66.9%), obesity (49.4%) and hypertension (38.8%). There were poorly controlled patients in 38.8%. A link was found between T2DM and neuropathy (p = 0.014). Painful diabetes was related to the quality of glycemic control (p = 0.007), and hypertension (p = 0.021). A link was also found between tobacco consumption (p < 0.001), male (p < 0.001), and urogenital autonomic neuropathy. Conclusion: Diabetic neuropathies are very common in our context and could be a haunting to the practitioner with the progression of diabetes and its corollary of degenerative complications. There was a significant association between Type 2 Diabetes mellitus and the presence of peripheral diabetic neuropathy.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LY23H050005Zhejiang Medical Technology Project,No.2022RC009,No.2023XY238,and No.2024KY645.
文摘Diabetic gastrointestinal autonomic neuropathy(DGAN)is a common and debilitating complication of diabetes,characterized by autonomic dysfunction in the gastrointestinal system.The complex pathophysiology of DGAN involves neuronal injury that is intrinsically linked to gut dysbiosis.Multiple factors,including hyperglycemia,oxidative stress,and inflammation,significantly contribute to neuronal damage,manifesting as symptoms such as delayed gastric emptying,diarrhea,and constipation.Recent studies have demonstrated that patients with diabetes experience substantial alterations in gut microbiota composition,potentially exacerbating gastrointestinal symptoms.Microbial metabolites may modulate neurotransmitter synthesis and release,directly affecting autonomic nerve function,while dysbiosis amplifies oxidative stress and inflammation,further compromising the enteric nervous system and worsening DGAN.Advances in multi-omics technologies now provide deeper insights into molecular mechanisms of DGAN and its interactions with microbiota.Early diagnosis leveraging biomarkers,gut microbiota analysis,and advanced imaging promises more effective interventions.Emerging therapeutic strategies targeting oxidative stress,inflammation,and gut microbiota represent promising approaches for managing DGAN.Future research should focus on large-scale,multi-ethnic studies and therapies targeting specific microbial metabolites to refine diagnosis and treatment approaches.
文摘Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent research highlights therole of epigenetic markers including DNA methylation, histone modifications,and non-coding RNAs in regulating inflammatory responses, neuronal degeneration,and tissue repair. This review explores the epigenetics of DN and DFUs,emphasizing key regulatory pathways that influence disease progression andwound healing outcomes. Genome-wide DNA methylation studies reveal acceleratedepigenetic aging and metabolic memory effects in DN, contributing tosensory neuron dysfunction and neuropathic pain. Epigenetic dysregulation ofinflammatory mediators such as Toll-like receptors and the Nod-like receptorfamily, pyrin domain-containing 3 inflammasome further exacerbates neuronaldamage and delays wound healing. Additionally, histone deacetylases play apivotal role in oxidative stress regulation via the Nrf2 pathway, which is critical for both neuronal protection and angiogenesis in DFUs. Non-coding RNAs, particularly microRNAs (miRNAs),long non-coding RNAs (lncRNAs), and circular RNAs, are emerging as central regulators of the epigeneticcrosstalk between DN and DFUs. Several miRNAs, including miR-146a-5p and miR-518d-3p, are implicated inneuropathy severity, while lncRNAs such as nuclear enriched abundant transcript 1 modulate angiogenesis andwound repair. Cellular reprogramming of DFU fibroblasts has also been shown to induce pro-healing miRNAsignatures, offering potential therapeutic avenues. Furthermore, recent whole-genome and transcriptomic analysesof DFU-derived monocytes and Charcot foot lesions reveal unique epigenetic signatures that may serve as biomarkersfor early detection and personalized interventions. This epigenetic interplay between DN and DFUpathogenesis not only enhances our knowledge of disease mechanisms but also opens avenues for targetedepigenetic therapies to improve clinical outcomes.
基金Supported by the Youth Fund for Specialized Clinical Research of the Health Commission,No.20214Y0149.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is the most prevalent complication of type 2 diabetes mellitus(T2DM).Due to a lack of specific biomarkers,the early diagnosis of this disorder is limited.AIM To identify and validate serum amino acids that could discriminate T2DM patients with DPN from those without DPN.METHODS T2DM patients with DPN,T2DM patients without DPN,and healthy controls were recruited for this study.The participants comprised two nonoverlapping cohorts:A training cohort(DPN=84 participants,T2DM=82 participants,normal=50 participants)and a validation cohort(DPN=112 participants,T2DM=93 participants,normal=58 participants).A prediction model of the ability of serum amino acids to distinguish DPN from T2DM was established using a logistic regression model,and area under the curve(AUC)analysis was used to evaluate the diagnostic ability of the model.In addition,the serum amino acid levels of 13 DPN patients were also detected before treatment and after 3 months of treatment.RESULTS A clinical detection method for the diagnosis of DPN based on a biomarker panel of three serum amino acids and diabetes duration was developed.The diagnostic model demonstrated AUC values of 0.805(95%CI:0.739-0.871)and 0.810(95%CI:0.750-0.870)in the training and verification cohorts,respectively.In the identification of T2DM patients and normal controls,the AUC values were 0.891(95%CI:0.836-0.945)and 0.883(95%CI:0.832-0.934)in the training and validation cohorts,respectively.Arginine and tyrosine levels were increased after treatment,whereas aspartic acid levels were decreased after treatment.CONCLUSION This study successfully identified and validated the metabolomic significance of arginine,tyrosine,and glutamic acid as potential biomarkers for diagnosing DPN.These findings are particularly valuable,as they establish a foundational step toward developing the first routine laboratory test for DPN.Moreover,the diagnostic model that was constructed in this study effectively distinguishes DPN patients from those with T2DM without neuropathy,thereby potentially facilitating early diagnosis and intervention.
基金Supported by the Key Project of the Affiliated Hospital of North Sichuan Medical College,No.2023ZD008the Project of the Doctoral Initiation Fund,No.2023GC002+3 种基金Scientific Research and Development Program Project,No.2024PTZK008Sichuan Province Clinical Key Specialty Construction Project,No.2023GZZKP002Science and Technology Project of Nanchong,No.22SXQT0364Research Development Plan Project of Affiliated Hospital of North Sichuan Medical College,No.2024MPZK003.
文摘BACKGROUND Diabetic neuropathy(DN)is a progressive disorder with limited effective treatment options.AIM To identify potential therapeutic targets for DN by integrating plasma proteomic and transcriptomic data.METHODS A comprehensive analytical framework was developed to identify multi-omics biomarkers of DN.Protein-protein interaction network and Gene Ontology analyses were performed to explore the biological functions of biomarkers.Tier 1 target proteins were further analyzed.Candidate drug prediction and molecular docking studies were conducted to identify potential treatments while assessing the side effects of key target proteins.The mediation of immune cells in the association between proteins and DN was examined through two-step network Mendelian randomization(MR)analysis.RESULTS Nine DN-associated proteins were identified by analyzing protein quantitative trait loci from extensive genome-wide association study data.BTN3A1 and MICB were confirmed using MR,summary data-based MR,and colocalization analyses.Of the nine,HSPA1B,PSMB9,BTN3A1,SCGN,NOTUM,and MICB showed negative associations with DN,whereas WARS,BRD2,and CSNK2B were positive.Gene Ontology analysis indicated enrichment in inflammatory response and neuronal injury pathways.BTN3A1 and MICB were identified as Tier 1 targets.Drug prediction and molecular docking analyses indicated cyclosporin A as a potential therapeutic candidate.Two-step network MR analysis showed that MICB mediated DN through human leukocyte antigen-DR++monocytes.These integrated findings point to an immune-mediated mechanism with translational potential and nominate BTN3A1 and MICB for focused functional validation.CONCLUSION Our integrated multi-omics approach identified two promising therapeutic targets for DN,laying the groundwork for new treatment strategies and enhancing our understanding of MICB’s role in DN.
基金supported by the Anhui Provincial Key Research and Development PlanThis study was supported by National Key Research and Development Program of China(No.2023YFF0724803)Yunnan Province“Xingdian Talent Support Program”Yunling Scholar Special Project(No.XDYC-YLXZ-2022-0027)Scientific Research Fund Project of Yunnan Provincial Education Department(No.2025Y0634,No.2025Y0627).
文摘Objective:Diabetic Peripheral Neuropathy(DPN)is a common chronic complication of diabetes that currently has no therapeutic recourse.Advanced DPN stages are characterized by severe symptoms that place a huge burden on patients and healthcare systems.To the best of our knowledge,research hotspots within the field of DPN are yet to be visually analyzed,and so is the exploration of developmental dynamics within the same discipline.Methods:Herein,DPN articles published between 2002 and 2022 were retrieved from the Web of Science Core Collection database.Following that,bibliometric analysis was performed on these articles using CiteSpace,VOSviewer,Microsoft Excel,and R-bibliometrix tools.Results:We retrieved 2,761 DPN articles involving 11,605 researchers from 1,140 institutions in 99 countries/regions.The United States was the country/region with the highest number of publications.The most productive author was Malik Rayaz A from the University of Manchester,which was the most productive institution.The most co-cited journals were Diabetes Care,Pain,and Neurology.On the other hand,#0 neuropathic pain,#1 neuropathic pain treatment and#2 peripheral neuropathy were the most clustered keywords in co-cited references.Based on the clustering of keywords,timeline graphs,and citation bursts,“risk”,“corneal confocal microscopy”and“systematic review”were identifi ed as the key issues for future DPN research.Conclusion:This article summarizes the current DPN research status and focus areas,reveals the future development trend,and points out potential research directions for DPN scholars.
文摘Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.
基金Key Project of Joint Special Funds for Applied Basic Research of Yunnan Provincial Department of Science and Technology Kunming Medical University,Grant/Award Number:2018FE001-(180)Clinical Research Center of the First People's Hospital of Yunnan Province,Grant/Award Number:2023YJZX-LN01+2 种基金Kunming University of Science and Technology School of Medicine Postgraduate Innovation FundResearch Plan of the National Natural Science Foundation of China,Grant/Award Number:82460210Provincial Key Clinical Specialty Platform of the First People's Hospital of Yunnan Province,Grant/Award Number:2024EKKFKT-04。
文摘Background:Diabetic retinal neuropathy(DRN)leads to significant visual impairment;however,no existing animal model fully replicates its neural alterations,and inconsistent induction protocols with high mortality rates hinder long-term investigations.Methods:Adult male rabbits were randomly assigned to four experimental groups,each receiving a single intravenous injection of varying doses of alloxan and one control group.The safety and efficacy of alloxan in inducing diabetes were evaluated to determine the optimal dose.At 9 weeks following injection with alloxan,retinal function was assessed using full-field electroretinography(ERG)and visual evoked potentials(VEPs).Retinal structure was examined in rabbits using spectral-domain optical coherence tomography(SD-OCT),Optos ultra-widefield(Optos UWF)false-color imaging,and widefield fundus fluorescein angiography(WF-FFA).Results:Rabbits in the 80 mg/kg alloxan group exhibited fewer complications,lower mortality,and a higher model success rate compared to other groups.At 9 weeks post-injection,these rabbits demonstrated significantly elevated hemoglobin A1c and total cholesterol(p<0.05)relative to controls.ERG revealed statistically significant reductions in oscillatory potential and b-wave amplitudes(p<0.05),while VEP indicated decreased P2 amplitude(p<0.001)and prolonged P2 latency(p<0.05).SD-OCT,Optos UWF imaging,and WF-FFA demonstrated no significant changes in vascular abnormalities.Additionally,Hematoxylin and Eosin staining revealed retinal swelling(p<0.05),and immunofluorescence confirmed glial activation and neuronal loss.Conclusions:A single intravenous injection of 80 mg/kg alloxan effectively and safely induced DRN in rabbits,resulting in neural retina damage,thereby establishing this model as an ideal model for DRN research.
基金supported by the Key Program of the Changji Prefecture Science and Technology Program(2023S04-10,2023S06-03).
文摘Purpose:To explore the clinical value of Electromyography(EMG)and Heart Rate Variability(HRV)in the diagnosis of early DPN and provide the basis for early diagnosis,treatment,and prevention of DPN.Methods:105 patients with type 2 diabetes mellitus(T2DM)in the Changji People’s Hospital were treated from January 2023 to December 2023.They were stratifi ed into DPN-symptomatic(DPN group,n=55)and DPN-asymptomatic(NDPN group,n=50)cohorts based on the presence or absence of clinically confi rmed diabetic peripheral neuropathy.The clinical biochemical indicators,nerve electromyography,and HRV parameters were obtained from electronic medical records,and diff erences in detection results were compared between the two groups.Logistic regression was applied to analyze the infl uencing factors of DPN in diabetes patients.The receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of EMG combined with other parameters for DPN.Results:From the results of the general information,diabetes duration,glycosylated hemoglobin(HbA1c),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)and FBG in the DPN group were significantly differences compared with the NDPN group(p<0.05).There were no statistically significant differences in gender,age years,uric acid,and other general data(p>0.05).Compared with the NDPN group,the motor nerve conduction velocity(MNCV),sensory nerve conduction velocity(SNCV)of the ulnar nerve,median nerve,and tibial nerve in the DPN group were statistically signifi cant(p>0.05).The DPN group had higher average F wave latency and H wave latency in the tested nerve,with statistical signifi cance(p<0.05).HRV parameters decreased signifi cantly(SDNN,rMSSD,PNN50,and SDANN,all p<0.05).ROC analysis showed that the area under the ROC curve(AUC)of the combined diagnosis of DPN by duration of diabetes,HbA1c,EMG,and HRV was 0.897,the accuracy was 82.86%,the sensitivity was 78.00%,and the specifi city was 87.27%.The AUC of the combined diagnosis of the four parameters for DPN was signifi cantly higher than that of each alone(p<0.05).Conclusion:The combination of EMG and HRV has a high value in the assessment of DPN and can be used for early assessment of the extent of the lesion.
基金supported by Pudong New Area Science and Technology Development Fund Special Research Project on the Livelihood of Institutions(No.PKJ2023-Y03)Pudong New Area Chinese Medicine Senior Teacher Training Program(No.PDZY-2023-0801)Talents Training Program of the Seventh People’s Hospital,Shanghai University of Traditional Chinese Medicine(No.JY2024-08).
文摘Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.
基金Supported by Capital’s Funds for Health Improvement and Research,No.2024-4-4135.
文摘BACKGROUND The trend of risk prediction models for diabetic peripheral neuropathy(DPN)is increasing,but few studies focus on the quality of the model and its practical application.AIM To conduct a comprehensive systematic review and rigorous evaluation of prediction models for DPN.METHODS A meticulous search was conducted in PubMed,EMBASE,Cochrane,CNKI,Wang Fang DATA,and VIP Database to identify studies published until October 2023.The included and excluded criteria were applied by the researchers to screen the literature.Two investigators independently extracted data and assessed the quality using a data extraction form and a bias risk assessment tool.Disagreements were resolved through consultation with a third investigator.Data from the included studies were extracted utilizing the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies.Additionally,the bias risk and applicability of the models were evaluated by the Prediction Model Risk of Bias Assessment Tool.RESULTS The systematic review included 14 studies with a total of 26 models.The area under the receiver operating characteristic curve of the 26 models was 0.629-0.938.All studies had high risks of bias,mainly due to participants,outcomes,and analysis.The most common predictors included glycated hemoglobin,age,duration of diabetes,lipid abnormalities,and fasting blood glucose.CONCLUSION The predictor model presented good differentiation,calibration,but there were significant methodological flaws and high risk of bias.Future studies should focus on improving the study design and study report,updating the model and verifying its adaptability and feasibility in clinical practice.
基金National Natural Science Foundation of China,No.82270881 and No.82200928National High-Level Hospital Clinical Research Funding,No.BJ-2023-124 and No.BJ-2023-130.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.
基金Supported by the Fundamental Research Grant Scheme of the Ministry of Higher Education,Malaysia,No.FRGS/1/2024/SKK10/USM/02/8.
文摘Diabetes mellitus(DM)and its complications continue to impose a substantial burden on healthcare systems worldwide.Diabetic neuropathy(DN)is one of the most common chronic microvascular and neurodegenerative complications of DM.It is clinically characterized by allodynia,hyperalgesia,and abnormal or absent nerve fiber sensation,which collectively contribute to poor quality of life,sleep disturbances,depression,and increased mortality.Although several pharmacological agents are available to alleviate DN-related symptoms,their limited long-term efficacy and adverse side effects underscore the urgent need for novel therapeutic approaches.This limitation may be attributed to an incomplete understanding of the underlying mechanisms of DN.Accumulating evidence has highlighted the contribution of glial cells including astrocytes,microglia,and oligodendrocytes to the pathogenesis of DN.However,the specific role of astrocytes remains insufficiently defined.Therefore,this review provides a comprehensive evaluation of current knowledge regarding astrocyte involvement in DN mechanisms,with the goal of clarifying their contribution to disease progression and identifying potential therapeutic targets.
基金Supported by Natural Science Foundation of Hunan Province,No.2023JJ60497Chinese Medicine Research Program of Hunan Province,No.2021169Xiangtan Medical Research Project Plan,No.2022-xtyx-34 and No.2022-xtyx-36.
文摘Diabetic peripheral neuropathy(DPN)is a common complication of diabetes and is characterized by sensory and motor impairments resulting from neural injury.Schwann cells(SCs),which are important for peripheral nerve function,are compromised under hyperglycemic conditions,leading to impaired axonal re-generation and demyelination.Autophagy,a cellular degradation process,is essential for SC function and significantly influences DPN progression.This article highlights the significance of autophagy in SCs and its potential as a pharmacotherapeutic target in DPN.We discuss the mechanisms of autophagy in SCs,including the mammalian target of rapamycin,adenosine monophosphate-activated protein kinase,and phosphatase and tensin homolog-induced putative kinase/parkin pathways,and their dysregulation in DPN.This article also exa-mines various natural products and chemical agents that modulate autophagy and enhance the efficacy of DPN treatment.These agents target key signaling pathways,such as adenosine monophosphate-activated protein kinase/mam-malian target of rapamycin and demonstrate potential in promoting nerve re-generation and restoring SC function.The roles of exosomes,long non-coding RNA,and proteins in the regulation of autophagy have also been explored.In conclusion,targeting autophagy in SCs is a promising strategy for DPN treatment and offers new insights into therapeutic interventions.Further research is war-ranted to fully exploit these targets for clinical applications.
