Treatment Of Diabetic Peripheral Neuropathy Research Articles

Evaluation of Tricyclic Antidepressant Deprescribing in the Treatment of Diabetic Peripheral Neuropathy within Federally Qualified Health Centers

BackgroundTricyclic antidepressants (TCAs) are a treatment option for diabetic peripheral neuropathy (DPN). Existing evidence demonstrates the prolonged use of TCA therapy increases the risk of cognitive decline and dementia, likely due to the anticholinergic effects of these medications. The anticholinergic activity is thought to contribute significantly to the observed increase in cognitive decline and dementia risks associated with long-term TCA use. There is little information available to describe the usage patterns of TCAs in DPN, particularly within underserved populations who receive care at Federally Qualified Health Centers (FQHCs). ObjectivesThe objective of this study was to characterize: 1) prescribing patterns of TCAs as a treatment for DPN and 2) evidence of deprescribing attempts in a FQHC population. MethodsA retrospective chart review of electronic medical record (EMR) data for patients at two different FQHCs was performed. A convenience sample of 100 adults ≥ 18 years of age was stratified into two age groups, 18-55 years, and 55+ years. All patients had a diagnosis of Type 1 or Type 2 diabetes mellitus and had been prescribed TCAs in the previous four years and had a visit with a primary care provider (PCP) in the past 12 months. ResultsThe study population was comprised of 100 individuals. Seventy-four of 100 were persistent users of TCAs at the time of data collection, and the mean duration of utilization was 54.8 months. In total, 104 TCAs were prescribed across 100 individual patients. Of all 104 prescribed TCAs, 66 (63%) were prescribed at a rate that exceeded thresholds associated with a higher risk of dementia. Black older adults prescribed TCAs were more likely to exceed this dose threshold. Conclusion65% of patients used TCAs with a strength, frequency, and duration that exceeded risk thresholds for dementia in an older adult population. Interventions preventing use of or deprescribing TCAs in patients with DPN should be conducted for the potential benefits of preventing or delaying cognitive impairment and promoting equitable care.

The efficacy and safety of electroacupuncture for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis.

Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus, which is the most common neuropathy worldwide. Owing to the inadequacies of existing treatment methods, managing DPN remains a significant challenge. Studies suggest that electroacupuncture (EA) could potentially serve as a beneficial alternative treatment for this condition. Nevertheless, there is still inadequate proof of its therapeutic effectiveness and safety. As a result, the goal of this protocol is to methodically compile the data pertaining to the effectiveness and security of EA in the management of DPN. To find appropriate randomized controlled trials (RCTs), nine reliable databases in the English and Chinese languages will be examined. RevMan5.3 will be used to combine the retrieved data and perform meta-analyses. The methodological quality of the included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. The Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be utilized to evaluate the degree of strength and certainty of the evidence. We will also perform publication bias, sensitivity and subgroup analyses. This protocol describes the intended scope and approach for a forthcoming systematic review and meta-analysis that will inform therapeutic decision-making by offering current information on the efficacy and safety of EA in the treatment of DPN. The results of the study will help standardize strategies for EA in the treatment of DPN.

Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials.

To assess the long-term effectiveness of Huangqi (Radix Astragali Mongolici, HQ)-based Traditional Chinese Medicine (TCM) in the treatment of diabetic peripheral neuropathy (DPN). Nine databases were searched to retrieve available randomized controlled trials that compared HQ-based TCM and Western Medicines in the treatment of DPN. The methodological quality of the included studies was assessed using the Cochrane bias risk tool, and RevMan 5.4 was used for data analysis. The effect estimates of interest were risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM [RR = 1.30, 95% CI (1.21, 1.40), P < 0.000 01] or HQ-based TCM combined with Western Medicines [RR = 1.25, 95% CI (1.19, 1.31), P < 0.000 01] exhibited higher total efficacy rates than individuals who received Western Medicine alone. The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores [MD =－1.50, 95% CI (－1.83, －1.17), P < 0.000 01], and reduced serum interleukin 6 [SMD = －0.57, 95% CI (－0.87, －0.27), P = 0.0002] and tumor necrosis factors-α levels [SMD = －0.60, 95% CI (－0.95, －0.25), P = 0.0009]. In addition, both HQ-based TCM and HQ-based TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone. In terms of blood lipids, oxidative stress and adverse drug reactions, there were no significant differences between the HQ-based TCM groups and the Western Medicine control group. The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN, although further well-designed RCTs are required to validate these findings.

Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial

IntroductionSpecific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms...

Role of Regenerative Therapeutics in Diabetic Peripheral Neuropathy: Current Advances and Future Prospects

Diabetes is a chronic metabolic condition that has far-reaching consequences for human health. If there is no appropriate therapeutic treatment, diabetic peripheral neuropathy  might lead to foot ulceration and limb amputation. Conventional pharmacological therapy have weak anti-DPN activity. By stimulating nerve regeneration, addressing underlying causes of the disorder, and alleviating symptoms, stem cell therapy for diabetic peripheral neuropathy has the potential to alter the management of this debilitating illness. One of its most significant advantages is its ability to regenerate damaged nerves, as stem cells may differentiate into a variety of cell types, including neurons and supporting cells. Preclinical and early-phase clinical research has resulted in improvements in nerve conduction, pain alleviation, and sensory function in patients with diabetic peripheral neuropathy. Stem cell therapy can be tailored to each patient's specific ailment, ensuring personalized care that improves therapeutic outcomes. Future research may uncover further benefits and applications for stem cell treatment, such as refining stem cell source selection, experimenting with novel delivery systems, and capitalizing on tissue engineering advances. Combining stem cell therapy with gene editing or bioengineering procedures may improve regenerative potential in the treatment of diabetic peripheral neuropathy. To completely reap the benefits of stem cell therapy in diabetic peripheral neuropathy, obstacles must be overcome and treatment procedures must be improved. Stem cell therapy has the potential to revolutionize the treatment of diabetic peripheral neuropathy by encouraging nerve regeneration, and symptom relief. The present review discusses the noteworthy developments in various regenerative therapies for diabetic peripheral neuropathy.

Update on Treating Painful Diabetic Peripheral Neuropathy: A Review of Current US Guidelines with a Focus on the Most Recently Approved Management Options.

Painful diabetic peripheral neuropathy (DPN) is a highly prevalent and disabling complication of diabetes that is often misdiagnosed and undertreated. The management of painful DPN involves treating its underlying cause via lifestyle modifications and intensive glucose control, targeting its pathogenesis, and providing symptomatic pain relief, thereby improving patient function and health-related quality of life. Four pharmacologic options are currently approved by the US Food and Drug Administration (FDA) to treat painful DPN. These include three oral medications (duloxetine, pregabalin, and tapentadol extended release) and one topical agent (capsaicin 8% topical system). More recently, the FDA approved several spinal cord stimulation (SCS) devices to treat refractory painful DPN. Although not FDA-approved specifically to treat painful DPN, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, gabapentinoids, and sodium channel blockers are common first-line oral options in clinical practice. Other strategies may be used as part of individualized comprehensive pain management plans. This article provides an overview of the most recent US guidelines for managing painful DPN, with a focus on the two most recently approved treatment options (SCS and capsaicin 8% topical system), as well as evidence for using FDA-approved and guideline-supported drugs and devices. Also discussed are unmet needs for this patient population, and evidence for potential future treatments for painful DPN, including drugs with novel mechanisms of action, electrical stimulation devices, and nutraceuticals.

Comparative Analysis of the Efficacy of Spinal Cord Stimulation and Traditional Debridement Care in the Treatment of Ischemic Diabetic Foot Ulcers: A Retrospective Cohort Study

BACKGROUND AND OBJECTIVES: Spinal cord stimulation (SCS) is an effective treatment for diabetic peripheral neuropathy. The purpose of this study was to investigate the effectiveness of SCS in the treatment of ischemic diabetic foot ulcers. METHODS: In this retrospective study, the SCS group comprised 102 patients with ischemic diabetic foot who were treated with SCS for foot ulcers and nonhealing wounds due to severe lower limb ischemia. The traditional debridement care (TDC) group comprised 104 patients with ischemic diabetic foot who received only TDC. Strict screening criteria were applied. The assignment of patients to either group depended solely on their willingness to be treated with SCS. Secondary end points were transcutaneous partial pressure of oxygen (PtcO2), ankle-brachial index (ABI), and color Doppler of the lower limb arteries in the feet at 6 months and 12 months after treatment. The primary end point was the amputation. RESULTS: The dorsal foot PtcO2 and ABI of the patients in the SCS group were significantly improved at 6 months and 12 months postoperation (P &lt; .05). The therapeutic efficacy was significantly better than that of the TDC group over the same period of time (P &lt; .05). The degree of vasodilation of the lower limb arteries (ie, femoral, popliteal, posterior tibial, and dorsalis pedis arteries) on color Doppler was higher in the SCS group than in the TDC group (P &lt; .05). The odds ratios for total amputation at 6 and 12 months postoperatively in the SCS group were 0.45 (95% CI, 0.19-1.08) and 0.17 (95% CI, 0.08-0.37), respectively, compared with the TDC group. CONCLUSION: SCS improved symptoms of lower limb ischemia in ischemic diabetic feet and reduced the rate of toe amputation by increasing PtcO2, ABI, and arterial vasodilation in the lower limbs.

Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology.

Xuebifang (XBF), a potent Chinese herbal formula, has been employed in managing diabetic peripheral neuropathy (DPN). Nevertheless, the precise mechanism of its action remains enigmatic. The primary objective of this investigation is to employ a bioinformatics-driven approach combined with network pharmacology to comprehensively explore the therapeutic mechanism of XBF in the context of DPN. The active chemicals and their respective targets of XBF were sourced from the TCMSP and BATMAN databases. Differentially expressed genes (DEGs) related to DPN were obtained from the GEO database. The targets associated with DPN were compiled from the OMIM, GeneCards, and DrugBank databases. The analysis of GO, KEGG pathway enrichment, as well as immuno-infiltration analysis, was conducted using the R language. The investigation focused on the distribution of therapeutic targets of XBF within human organs or cells. Subsequently, molecular docking was employed to evaluate the interactions between potential targets and active compounds of XBF concerning the treatment of DPN. The study successfully identified a total of 122 active compounds and 272 targets associated with XBF. 5 core targets of XBF for DPN were discovered by building PPI network. According to GO and KEGG pathway enrichment analysis, the mechanisms of XBF for DPN could be related to inflammation, immune regulation, and pivotal signalling pathways such as the TNF, TLR, CLR, and NOD-like receptor signalling pathways. These findings were further supported by immune infiltration analysis and localization of immune organs and cells. Moreover, the molecular docking simulations demonstrated a strong binding affinity between the active chemicals and the carefully selected targets. In summary, this study proposes a novel treatment model for XBF in DPN, and it also offers a new perspective for exploring the principles of traditional Chinese medicine (TCM) in the clinical management of DPN.

Effectiveness of platelet rich plasma (PRP) treatment and its comparison with pregabalin in painful diabetic polyneuropathy: A randomized controlled clinical trial

Background &amp; objective: The most common consequence of diabetes mellitus (DM) is diabetic peripheral neuropathy (DPN), and it has serious clinical implications that can affect patients' quality of life. There is an urgent need to to discover new methods of treatment, as the medications currently in use for prevention and treatment of DPN are only partially effective and have frequent adverse effects. We aimed to determine and compare the effect of platelet rich plasma (PRP) injection on acupuncture points and pregabalin in painful DPN.&#x0D; Methodology: A randomized controlled trial was conducted at Iffat Anwar Medical Complex. All the clinically diagnosed patients having neuropathic sign and symptoms of DPN, with type 2 DM diagnosed having an HbA1c level greater than 7.5, both genders aged between 40-70 y were enrolled in the study. After the written informed consent, a total of 60 patients were randomly divided into two groups in a 1:1 ratio. Group I received PRP injections on acupuncture points and Group II received 75 mg pregabalin PO twice daily. The PRP injection treatment was given once a month for three months. Follow up of all patients was conducted every month till three months and after one year for final assessment. All the data was entered and analyzed by SPSS 25.0. The difference among pain, SF-36, sleep quality scale among groups was compared by independent sample t test and before and after difference was observed by paired sample t-test. P &lt; 0.05 was considered as significant.&#x0D; Results: The VAS scores were significantly decreased in Group I (from 7.47 ± 1.27 to 3.67 ± 1.09; P &lt; 0.05) as compared to Group II (7.30 ± 1.59 to 5.20 ± 1.58, P &lt; 0.05). The neuropathic symptoms scale also showed significant improvement (Group I: 13.50 ± 50 to 8.50 ± 2.30 vs. Group II: 14.93 ± 2.55 to 9.83 ± 2.17, P &lt; 0.05), as well as the quality of life (Group I: 67.77 to 31.50 ± 9.24 vs. Group II:69.37 ± 11.7to 41.20 ± 12.16, P &lt; 0.05) and sleep quality scale (Group I:49.53 ± 12.4 to 27.30 ± 8.03 vs. Group II: 52.13 ± 10.9to 32.60 ± 7.103, P &lt; 0.05).&#x0D; Conclusion: We conclude that the treatment of diabetic peripheral neuropathy with platelet rich plasma injections at acupuncture points significantly improves the pain scores, quality of sleep and neuropathic symptoms as compared to conventional treatment with 75 mg pregabalin PO twice daily.&#x0D; Abbreviations: DM- Diabetes Mellitus; DPN- Diabetic Polyneuropathy; LANSS- Leeds Assessment of Neuropathic Symptoms and Signs; PRP- Platelet Rich Plasma; QoL- Quality of Life; SQS- Sleep Quality Scale&#x0D; Key words: Acupuncture; Diabetic Poly Neuropathy; Pain; PRP injections; Quality of Life&#x0D; Citation: Anwar S, Hassan MW, Shaukat GR, Tirmzi F, Saeed MU, Aslam M. Effectiveness of platelet rich plasma (PRP) treatment and its comparison with pregabalin in painful diabetic polyneuropathy: A randomized controlled clinical trial. Anaesth. pain intensive care 2024;28(1):44-49; DOI: 10.35975/apic.v28i1.2280&#x0D; Received: August 07, 2023; Reviewed: August 08, 2923; Accepted: December 21, 2023

Protective effect of alpha-lipoic acid and epalrestat on oxaliplatin-induced peripheral neuropathy in zebrafish.

Oxaliplatin is a platinum-based anti-cancer drug widely used in colorectal cancer patients, but it may cause peripheral neuropathy. As one of the main causes of oxaliplatin-induced peripheral neuropathy (OPN) is oxidative stress, which is also a key factor causing diabetic peripheral neuropathy (DPN), the aim of this study was to evaluate the preventive effects of alpha-lipoic acid (ALA) and epalrestat (EP), which are used for the treatment of DPN, in an OPN zebrafish model. Tg(nbt:dsred) transgenic zebrafish, with sensory nerves in the peripheral lateral line, were treated with oxaliplatin, oxaliplatin/EP, and oxaliplatin/ALA for 4 days. A confocal microscope was used to visualize and quantify the number of axon bifurcations in the distal nerve ending. To analyze the formation of synapses on sensory nerve terminals, quantification of membrane-associated guanylate kinase (MAGUK) puncta was performed using immunohistochemistry. The number of axon bifurcations and intensity of MAGUK puncta were significantly reduced in the oxaliplatin-treated group compared with those in the embryo medium-treated group. In both the oxaliplatin/EP and oxaliplatin/ALA-treated groups, the number of axon bifurcations and intensity of MAGUK puncta were greater than those in the oxaliplatin-treated group (p < .0001), and no significant difference was observed between larvae treated with oxaliplatin/ALA 1 μM and oxaliplatin/EP 1 μM (p = .4292). ALA and EP have protective effects against OPN in zebrafish. Our findings show that ALA and EP can facilitate more beneficial treatment for OPN.

NAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice.

Abnormal NAD+ signaling has been implicated in axonal degeneration in diabetic peripheral neuropathy (DPN). We hypothesized that supplementing NAD+ precursors could alleviate DPN symptoms through increasing the NAD+ levels and activating the sirtuin-1 (SIRT1) protein. To test this, we exposed cultured Dorsal Root Ganglion neurons (DRGs) to Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), which increased the levels of NAD+, the SIRT1 protein, and the deacetylation activity that is associated with increased neurite growth. A SIRT1 inhibitor blocked the neurite growth induced via NR or NMN. We then induced neuropathy in C57BL6 mice with streptozotocin (STZ) or a high fat diet (HFD) and administered NR or NMN for two months. Both the STZ and HFD mice developed neuropathy, which was reversed through the NR or NMN administration: sensory function improved, nerve conduction velocities normalized, and intraepidermal nerve fibers were restored. The NAD+ levels and SIRT1 activity were reduced in the DRGs from diabetic mice but were preserved with the NR or NMN treatment. We also tested the effect of NR or NMN administration in mice that overexpress the SIRT1 protein in neurons (nSIRT1 OE) and found no additional benefit from the addition of the drug. These findings suggest that supplementing with NAD+ precursors or activating SIRT1 may be a promising treatment for DPN.

Co-treatment of Astragaloside IV with Vitamin D in Diabetic Peripheral Neuropathic Rats: Protective Effects and Potential Mechanisms.

The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated. The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques. Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert antioxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin-angiotensin-aldosterone system, and promotion of β-cell sensitivity to insulin. The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.

Research Progress of Buyang Huanwu Decoction in the Treatment of Diabetic Peripheral Neuropathy

Research Progress of Buyang Huanwu Decoction in the Treatment of Diabetic Peripheral Neuropathy

Clinical Effect of Yiqi Huoxue Tongmai Decoction in the Treatment of Diabetic Peripheral Neuropathy

Clinical Effect of Yiqi Huoxue Tongmai Decoction in the Treatment of Diabetic Peripheral Neuropathy

[Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy].

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

Pathogenetic treatments for diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three cornerstones: 1) causal treatment with lifestyle modification, intensive diabetes therapy aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, 2) pathogenesis-oriented pharmacotherapy, and 3) symptomatic pain relief. Since symptomatic analgesic monotherapy only relieves the pain without targeting the underlying neuropathy and both has limited efficacy and is associated with adverse events, there is an unmet need for additional approaches derived from the pathogenetic concepts of DPN. Preclinical studies have suggested that diabetic neuropathy can be prevented or improved through the use of various agents that interfere with the pathophysiology of the underlying condition. Some of these encouraging findings could be translated successfully into the clinical setting. Efficacy and excellent safety were demonstrated in several meta-analyses (α-lipoic acid) and randomized clinical trials (benfotiamine, actovegin, epalrestat) in the treatment of symptomatic DPN. The NATHAN 1 trial demonstrated an improvement of neuropathic signs (deficits, impairments) after four years in asymptomatic DPN. These compounds are currently authorized for treatment of DPN in several countries. Long-term pivotal clinical trials should further establish their value as mono- and combination therapies in DPN.

Diagnostic biomarker for type 2 diabetic peripheral neuropathy via comprehensive bioinformatics analysis.

Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb amputation. The identification of noninvasive biomarkers for DPN may help early detection and individualized treatment of DPN. In this study, we identified differentially expressed genes (DEGs) between DPN and the control based on blood-source (GSE95849) and tissue-source gene expression profiles (GSE143979) from the Gene Expression Omnibus (GEO) database using limma, edgeR, and DESeq2 approaches. KEGGG and GO functional enrichments were performed. Hub genes and their correlation with infiltrating immune cells were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify hub gene expression. In total, 144 DEGs between DPN and the control were identified. Functional enrichment revealed that the DEGs were mainly enriched in immune-related pathways like the Fc epsilon receptor Ig signaling pathway. By protein-protein interaction (PPI) network analysis, FCER1G, SYK, ITGA4, F13A1, MS4A2, and PTK2B were screened as hub genes with higher expression in DPN patients, among which half were immune genes (FCER1G, PTK2B, and SYK). RT-qPCR demonstrated that mRNA expression of FCER1G, PTK2B, and SYK was significantly increased in patients with DPN compared with both diabetic nonperipheral neuropathy (DNN) and normal subjects. The area under the receiver operating characteristic (ROC) curve of FCER1G, PTK2B, and SYK was 0.84, 0.81, and 0.73, respectively, suggesting their great advantages as diagnostic biomarkers to predict the progression of neuropathy in T2DM. Further analysis indicated that the expression of FCER1G, PTK2B, and SYK was negatively correlated with the cell proportion of significantly altered resting natural killer cells, T follicular helper cells, and activated mast cells, but positively correlated with monocytes. Our findings demonstrated FCER1G, PTK2B, and SYK are potential diagnostic biomarkers and therapeutic targets for DPN, which provides new insight into DPN pathogenesis and therapies.

Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy.

Accumulating evidence shows that Schwann cells' (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit‑8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN.

Efficacy and safety of Buyang Huanwu decoction for diabetic peripheral neuropathy: a systematic review and Metaanalysis.

To evaluate the efficacy and safety of Buyang Huanwu decoction (BYHWD) in treating diabetic peripheral neuropathy (DPN). Eight electronic databases, including China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, Chinese Biomedical Literature Database, Cochrane Library, Embase, Web of Science, and PubMed, were searched for randomized controlled trials (RCTs) of BYHWD to treat DPN. We identified all RCTs related to BYHWD and those on the treatment of DPN with the combination of mecobalamin. RevMan software was used for the statistical analysis. Twentyone RCTs with a total of 1945 patients were included. The methodological quality of the literature included was low. Metaanalysis showed that the efficacy of the treatment group was significantly better than that of the control group in the treatment of DPN with BYHWD [risk ratio () = 0.33, 95% (0.27, 0.40), 11.25, 0.000 01]. The median nerve of median motor nerve conduction velocity (MNCV) [mean difference () = 4.16, 95% (1.35, 6.98)] and median sensory NCV (SNCV) [(= 3.28, 95% (2.35, 4.22)] were improved in the treatment group. The MNCV in the common peroneal nerve [(= 1.63, 95% (0.39, 2.87)] and SNCV [(= 4.56, 95% (3.16, 5.97)] were significantly higher than those in the control group ( 0.01). Plasma viscosity [(= －0.15, 95% (－0.20, －0.09), 5.17, 0.01)], whole blood high shear [(= 0.83, 95% (1.56, －0.11), 2.26, 0.02)]and whole blood low shear [(= 1.61, 95% (2.28, 0.94), 4.68, 0.01)] decreased significantly after treatment. There was no significant difference in fasting blood glucose [(= 0.42, 95% ( 0.89, 0.05), 1.76, 0.08)] between the treatment and control groups; postprandial blood glucose [(= 0.62, 95% ( 1.19, 0.05), 2.12, 0.03)] decreased significantly. No significant difference was found in the blood lipid levels between the treatment and control groups, including triglycerides [(= 0.21, 95% (0.52, 0.10), 1.34, 0.18)] and cholesterol [(= 0.13, 95% ( 0.27, 0.00), 1.92, 0.06)]. Of the 21 RCTs, only five reported adverse reactions, and four studies reported the length of followup. No serious adverse events were reported. None of the studies reported the quality of life and economic conditions. Our study suggests that BYHWD has a significant therapeutic effect on DPN. Highquality, largescale RCTs are needed to provide more reliable evidence.

Digital Nerve Care Forum: Innovative Healthcare Professionals Education on Neuropathy.

Neuropathy is a common complication of diabetes, rarely detected on time, often deprioritized by treating physicians, and hence rarely managed in time, leading to avoidable complications which can be limb and life-threatening. Despite introducing new diagnostic tests, novel potential bio parameters, and a series of relatively small intervention studies utilizing detailed phenotypic profiling, the management of diabetic neuropathy (DN) and painful DN has remained unchanged due to misdiagnosis. The diagnostic complexity of diabetic peripheral neuropathy (DPN), variation in patient response to treatment, and regulatory pressures to meet data-driven quality metrics for diabetes management all likely contributes to the underdiagnosis and treatment of DPN in clinical practice. Educating the primary healthcare providers and diabetic trainers would help improve the number of diagnosed DPN cases as these practitioners lead public health literacy. The digital nerve care forum (NCF) is an educational initiative created by clinical experts and Procter and Gamble (P&G) health academy. Its primary aim is to generate awareness amongst healthcare practitioners (HCPs) about early diagnosis and timely management of DPN. Since its inception in October 2020, NCF has conducted 143 engagements; 39 neuropathy case puzzles, four interactive case-based discussions, two diagnostic workshops, four mentor-mentee nerve talk shows, two intercountry nerve talk shows, two global neuropathy awareness week initiatives, three nerves of steel (Women's Day special engagements), and 17 NCF times (Newsletters). This online forum is hosted on a global HCP education and upskilling platform, MediSage, which offers these educational resources to HCPs worldwide for free. It has helped create a community of 254, 714 HCPs from 86 countries across six continents supported by 30 neuropathy experts from seven countries. With a repeated viewership of 53% of HCPs engaging continuously, NCF empowers this community to improve diabetic patient care. Activities that increase disease awareness and highlight the importance of diabetic nerve health have been the key objectives behind the several educational programs on NCF. To drive this continuum, these digital programs are now becoming more phygital and impactful than ever. Therefore, earlier detection of DPN in at-risk individuals and those with prediabetes or type 2 diabetes is recommended for better management through optimal intervention and lifestyle changes and to prevent future complications of untreated DPN. How to cite this article: Kalra S, Tiwaskar M, Shrestha D, et al. Digital Nerve Care Forum: Innovative Healthcare Professionals Education on Neuropathy. J Assoc Physicians India 2023;71(10):89-92.