RESUMEN
BACKGROUND AND PURPOSE: Diabetic polyneuropathy is a long-standing microvascular complication of diabetes that affects the postural control and functional mobility of patients. There are other microvascular complications, including pulmonary complications that reduce lung function. Multifactorial Inspiratory Muscle Training (IMT) can act as a home-based technique targeted to affect both these complications. This study aims to determine the effects of IMT on respiratory and functional parameters in diabetic polyneuropathy patients. METHODS: This is a Pre-Test Post-Test Randomized Controlled Trial (NCT#04947163) with 62 diabetic polyneuropathy patients. Each was randomly assigned to the IMT or sham-IMT group. Both the groups performed OTAGO exercises , with the sham-IMT group performing IMT at 15% of baseline maximal inspiratory pressure (MIP), whereas IMT were trained at 50% of baseline MIP as an initial intensity, which was increased as per the tolerance of patients. Both groups performed training for 12 weeks. The study investigated diaphragmatic strength, pulmonary function, functional capacity through 6MWT, 30s sit to stand test and anterior trunk muscle endurance tested through sit up test as outcome variables. Data was analysed on SPSS v26 at the significance level of 0.0.5. RESULTS: The IMT group significantly improved diaphragmatic strength, pulmonary function, 6MWT and anterior trunk muscle endurance when compared to the sham-IMT group. CONCLUSION: The study concluded that home-based IMT can improve pulmonary parameters including diaphragmatic strength and lung function as well as functional parameters including functional capacity in patients with diabetic polyneuropathy. The study was registered at ClinicalTrials.gov, NCT#04947163.
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Ejercicios Respiratorios , Neuropatías Diabéticas , Fuerza Muscular , Músculos Respiratorios , Humanos , Masculino , Femenino , Neuropatías Diabéticas/rehabilitación , Neuropatías Diabéticas/fisiopatología , Persona de Mediana Edad , Fuerza Muscular/fisiología , Músculos Respiratorios/fisiopatología , Pruebas de Función Respiratoria , Diafragma/fisiopatología , Anciano , AdultoRESUMEN
Objective: The aim of this study is to assess the effectiveness of foot skin protection technology in elderly patients with diabetic peripheral neuropathy. Methods: The foot skin protection technology was developed based on a comprehensive literature review and preliminary research conducted by our research team. Subsequently, 88 elderly patients with diabetic peripheral neuropathy and experiencing foot skin problems were recruited from two community health service centers in Shanghai. Using a random number table, the participants were randomly assigned to either the control group or the experimental group. Patients in the experimental group received foot skin protection technology interventions, while those in the control group received standard community nursing guidance for a duration of 3 months. The incidence, severity, and discomfort associated with foot skin problems were evaluated before and after the intervention period in both groups. Results: The incidence, severity, and discomfort of foot skin problems notably reduced in the experimental group (all P< 0.05). Conclusion: The foot skin protection technology demonstrates significant potential in enhancing foot skin condition.
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Pie Diabético , Neuropatías Diabéticas , Humanos , Masculino , Anciano , Femenino , Neuropatías Diabéticas/prevención & control , Pie Diabético/prevención & control , Persona de Mediana Edad , China/epidemiología , Pie , Anciano de 80 o más AñosRESUMEN
INTRODUCTION: In India, the prevalence of diabetes mellitus neuropathy was reported to be as high as 30%. Eight percentage of the diabetic population suffer from foot ulceration and 1.8% have amputations. Popliteal nerve block can be potentially used for foot and ankle surgery with several advantages. AIM: To compare analgesic duration of an ultrasound (US)-guided popliteal sciatic nerve block between diabetics with neuropathy and nondiabetics without neuropathy. PATIENTS AND METHODS: Participants were allocated into two groups for popliteal sciatic nerve blocks under US guidance. The primary outcome was the duration to onset of sensory and motor blockade. The secondary outcome was the duration to rescue analgesic and the visual analog scale scoring within 24 h. Hemodynamic outcomes were also monitored along with the above variables. RESULTS: It was observed that the onset of sensory blockade was faster in participants with diabetes mellitus with peripheral neuropathy as compared to the nondiabetic participants and the duration for onset of motor blockade in dorsiflexion was faster in diabetic patients as compared to the nondiabetic patients (17.48 ± 3.21 min). However, there was no significant changes when comparing the onset of duration to loss of plantar flexion, in diabetics (17.86 ± 2.29 min) versus in nondiabetics (18.51 ± 3.32 min). The duration for rescue analgesics was found to be longer in diabetic participants (13.19 ± 2.14 h) as compared to the nondiabetic participants (11.44 ± 1.86 h). No differences were observed in the hemodynamic changes and the complications associated with local anesthetics in either group. CONCLUSION: Diabetic patients with neuropathy have faster onset of blockade when compared to nondiabetic patients without neuropathy which may be due to the degenerative condition of the peripheral nerves in them. The hemodynamic parameters do not play a role in defining the outcome of the block.
Résumé Introduction:En Inde, la prévalence de la neuropathie liée au diabète sucré atteignait 30 %. Huit pour cent de la population diabétique souffrent d'ulcères du pied et 1,8 % sont amputés. Le bloc du nerf poplité peut être potentiellement utilisé pour la chirurgie du pied et de la cheville avec plusieurs avantages.Objectif:Comparer la durée analgésique d'un bloc du nerf sciatique poplité guidé par échographie (É.-U.) entre des diabétiques atteints de neuropathie et des non diabétiques sans neuropathie.Patients et méthodes:Les participants ont été répartis en deux groupes pour les blocs du nerf sciatique poplité sous la direction des États-Unis. Le critère de jugement principal était la durée jusqu'à l'apparition du blocus sensoriel et moteur. Le résultat secondaire était la durée nécessaire pour sauver l'analgésique et l'échelle visuelle analogique après 24 h. Les résultats hémodynamiques ont également été surveillés avec les variables ci-dessus.Résultats:Il a été observé que l'apparition du blocage sensoriel était plus rapide chez les participants atteints de diabète sucré avec neuropathie périphérique que chez les participants non diabétiques et (la durée d'apparition du blocage moteur en dorsiflexion était plus rapide chez les patients diabétiques que chez les patients non diabétiques (Cependant, il n'y a eu aucun changement significatif en comparant le début de la durée à la perte de flexion plantaire, chez les diabétiques (17,86 ± 2,29 min) versus chez les non diabétiques (18,51 ± 3,32 min). La durée des analgésiques de secours a été trouvée être plus longue chez les participants diabétiques (13,19 ± 2,14 h) par rapport aux participants non diabétiques (11,44 ± 1,86 h). Aucune différence n'a été observée dans les changements hémodynamiques et les complications associées aux anesthésiques locaux dans les deux groupes.Conclusion:Patients diabétiques atteints de neuropathie ont un début de blocage plus rapide que les patients non diabétiques sans neuropathie, ce qui peut être dû à l'état dégénératif des nerfs périphériques chez eux. Les paramètres hémodynamiques ne jouent aucun rôle dans la définition de l'issue du bloc.
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Neuropatías Diabéticas , Bloqueo Nervioso , Nervio Ciático , Humanos , Bloqueo Nervioso/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Dimensión del Dolor , Ultrasonografía Intervencional/métodos , Resultado del Tratamiento , India/epidemiología , Factores de Tiempo , Anestésicos Locales/administración & dosificación , Estudios de Casos y ControlesRESUMEN
Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. As a new detection method for DPN, corneal confocal microscopy (CCM) is characterised by rapid, non-invasive, sensitive, and quantitative characteristics, as well as good repeatability. By detecting changes in the corneal nerves, DPN can be diagnosed early, and the severity of neuropathy evaluated. It is currently an ideal DPN evaluation method and has good clinical application prospects. This paper reviews the application and progress of CCM in the evaluation of DPN and summarises the evaluation methods of CCM, corneal nerve, and DPN to provide new ideas for the clinical diagnosis and treatment of DPN.
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Córnea , Neuropatías Diabéticas , Microscopía Confocal , Humanos , Microscopía Confocal/métodos , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/diagnóstico por imagen , Córnea/patología , Córnea/diagnóstico por imagen , Córnea/inervaciónRESUMEN
BACKGROUND: Proprioceptive disorders may occur when thick fibers are affected in diabetic neuropathy. This can lead to impaired joint stabilization and increased risk of falls and fractures. We evaluated joint position sense (JPS) in diabetic patients to detect those at risk for neuropathy earlier. METHODS: Sixty diabetic patients and 30 healthy individuals aged 30 to 60 years were included in the study and divided into three groups: 30 diabetic patients with peripheral neuropathy, 30 diabetic patients without peripheral neuropathy, and 30 nondiabetic control patients. Presence of neuropathy was determined electrophysiologically. Passive ankle JPS was evaluated by an isokinetic system in all three groups. Both 10° and 30° plantarflexion and 10° dorsiflexion were determined as target angles. The mean absolute angular error (MAAE) values for three trials with each angle were assessed by Kruskal-Wallis and Mann-Whitney U tests. RESULTS: The MAAEs with all of the angles were significantly higher in diabetic patients with peripheral neuropathy compared with diabetic patients without peripheral neuropathy and the control group (P < .001 for all of the comparisons). The MAAEs with right ankle 10° plantarflexion (P = .004) and 10° dorsiflexion (P = .007) and left ankle 10° plantarflexion (P = .008) were significantly higher in diabetic patients without peripheral neuropathy than in the control group. CONCLUSIONS: According to these results, ankle JPS may be deteriorated before determination of neuropathy electrophysiologically.Therefore, we believe that prophylactic programs in terms of the risk of falls and fractures by evaluating JPS need to be developed in the early stages of diabetes.
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Articulación del Tobillo , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Propiocepción , Humanos , Persona de Mediana Edad , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Adulto , Articulación del Tobillo/fisiopatología , Neuropatías Diabéticas/fisiopatología , Propiocepción/fisiología , Estudios de Casos y Controles , Dinamómetro de Fuerza Muscular , Rango del Movimiento Articular/fisiologíaRESUMEN
BACKGROUND: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. METHODS: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. RESULTS: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (ß 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. CONCLUSIONS: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Progresión de la Enfermedad , Conducción Nerviosa , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Conducción Nerviosa/fisiología , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangreRESUMEN
BACKGROUND: Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s. PURPOSE: Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. CONCLUSIONS: HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.
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Proteína HMGB1 , Hipoglucemiantes , Receptor para Productos Finales de Glicación Avanzada , Transducción de Señal , Humanos , Proteína HMGB1/metabolismo , Proteína HMGB1/antagonistas & inhibidores , Animales , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hipoglucemiantes/uso terapéutico , Mediadores de Inflamación/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Antiinflamatorios/uso terapéutico , Terapia Molecular Dirigida , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Resistencia a la Insulina , Receptores Toll-Like/metabolismo , Retinopatía Diabética/metabolismo , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/etiología , Retinopatía Diabética/prevención & control , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/tratamiento farmacológicoRESUMEN
Chronic inflammation is associated with diabetes and contributes to the development and progression of micro- and macrovascular complications. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to reduce levels of circulating inflammatory cytokines in non-diabetics by activating the cholinergic anti-inflammatory pathway. We investigated the anti-inflammatory potential of tVNS as a secondary endpoint of a randomized controlled trial in people with diabetes (NCT04143269). 131 people with diabetes (type 1: n = 63; type 2: n = 68), gastrointestinal symptoms and various degrees of autonomic neuropathy were included and randomly assigned to self-administer active (n = 63) or sham (n = 68) tVNS over two successive study periods: (1) Seven days with four daily administrations and, (2) 56 days with two daily administrations. Levels of systemic inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-γ) were quantified from blood samples by multiplex technology. Information regarding age, sex, diabetes type, and the presence of cardiac autonomic neuropathy (CAN) was included in the analysis as possible confounders. No differences in either cytokine were seen after study period 1 and 2 between active and sham tVNS (all p-values > 0.08). Age, sex, diabetes type, presence of CAN, and baseline levels of inflammatory cytokines were not associated with changes after treatment (all p-values > 0.07). A tendency towards slight reductions in TNF-α levels after active treatment was observed in those with no CAN compared to those with early or manifest CAN (p = 0.052). In conclusion, tVNS did not influence the level of systemic inflammation in people with diabetes.
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Citocinas , Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Humanos , Estimulación del Nervio Vago/métodos , Masculino , Femenino , Persona de Mediana Edad , Estimulación Eléctrica Transcutánea del Nervio/métodos , Citocinas/sangre , Adulto , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Inflamación/terapia , Inflamación/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/sangre , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/sangreRESUMEN
BACKGROUND: Diabetes peripheral neuropathy (DPN) is mainly treated with diabetes as a whole, and there is no targeted treatment. Some studies have reported that adjuvant hyperbaric oxygen therapy (HBOT) for DPN has achieved a good effect, our study aimed to evaluate the clinical efficacy and safety of HBOT for DPN and provide reference for the clinic by using a systematic review and meta-analysis. METHODS: A comprehensive search was conducted across several databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet Database, Chinese BioMedical Database, China Scientific Journal Database, and Wanfang Database, for relevant randomized controlled trials published before July 2022. The population, intervention, comparison, outcomes, study design criteria were used to guide the selection of studies. Meta-analysis was performed using RevMan 5.4 and STATA 14.0, with odds ratios and mean differences along with 95% confidence intervals serving as measures of effect size. RESULTS: Fourteen randomized controlled trials were included in the final analysis, comprising 675 patients in the HBOT group and 648 in the standard therapy (ST) group. The HBOT group demonstrated a significantly higher effective treatment rate compared to the ST group (Pâ <â .001). Additionally, the HBOT group showed significant improvements in motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNVC) across multiple nerves: median nerve (PMNCVâ <â 0.001, PSNCVâ =â 0.001), ulnar nerve (PMNCVâ =â 0.02, PSNCVâ <â 0.001), peroneal nerve (PMNCVâ <â 0.001, PSNCVâ <â 0.001), and tibial nerve (PMNCVâ =â 0.001, PSNCVâ =â 0.008). Six adverse events were reported in the HBOT group, while no adverse events occurred in the ST group, with no significant difference between the 2 groups. Publication bias was identified in some outcome variables through funnel plots, Begger test, and Egger test. CONCLUSIONS: HBOT significantly enhances treatment efficacy and nerve conduction velocity in patients with DPN, with few adverse events, making it a safe and effective adjunctive therapy for DPN.
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Neuropatías Diabéticas , Oxigenoterapia Hiperbárica , Humanos , Oxigenoterapia Hiperbárica/métodos , Neuropatías Diabéticas/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoAsunto(s)
Neuropatías Amiloides Familiares , Neuropatías Diabéticas , Radiculopatía , Humanos , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Diabéticas/diagnóstico , Radiculopatía/diagnóstico , Radiculopatía/etiología , Diagnóstico Diferencial , Masculino , Persona de Mediana Edad , FemeninoRESUMEN
OBJECTIVE: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios. MATERIALS AND METHODS: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks α2-adrenergic receptors, and methysergide, which inhibits serotonergic receptors, during the formalin test. RESULTS: The oral intake of isorhamnetin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamnetin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphorylated CREB (p-CREB) levels caused by diabetic neuropathy. CONCLUSIONS: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CREB protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy.
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Analgésicos , Neuropatías Diabéticas , Formaldehído , Quercetina , Animales , Ratones , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/inducido químicamente , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Masculino , Modelos Animales de Enfermedad , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Yohimbina/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Naloxona/farmacología , Naloxona/uso terapéutico , Estreptozocina , Dimensión del Dolor/efectos de los fármacos , Relación Dosis-Respuesta a DrogaRESUMEN
OBJECTIVE: To explore the lifestyle-related characteristics of people having type 2 diabetes mellitus with peripheral neuropathy. METHODS: The phenomenological study was conducted from July 5 to September 18, 2021, at Sadabuan Health Centre, Batunadua Health Centre and Wek 3 Health Centre, Padangsidimpuan, Indonesia, and comprised diabetic neuropathy patients who had cognitive impairment, anxiety and depression. Data was collected using in-depth interviews. Data was analysed using Collaizi's method. RESULTS: There were 8 subjects with mean age 48.38±13,606 years (range: 27-65 years), and mean duration of diabetes was 6±3.207 years. The majority of participants in this study were women 6 (75%). There were 7 themes that emerged from the collected data: level of physical activity, diet, sleep pattern, habit of consuming sweet drinks, smoking habit, social interaction, and self-care. CONCLUSIONS: Diabetes mellitus patient with peripheral neuropathy had not been able to completely switch to a healthier lifestyle.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Ejercicio Físico , Estilo de Vida , Humanos , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Masculino , Neuropatías Diabéticas/psicología , Neuropatías Diabéticas/epidemiología , Indonesia/epidemiología , Anciano , Fumar/epidemiología , Fumar/psicología , Autocuidado/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Sueño , Depresión/epidemiología , Depresión/psicología , Dieta , Relaciones Interpersonales , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/psicología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Investigación CualitativaRESUMEN
Diabetic peripheral neuropathy (DPN) is a common nerve-damaging complication of diabetes mellitus. Effective treatments are needed to alleviate and reverse diabetes-associated damage to the peripheral nerves. Curcumin is an effective neuroprotectant that plays a protective role in DPN promoted by Schwann cells (SCs) lesions. However, the potential molecular mechanism of curcumin remains unclear. Therefore, our aim is to study the detailed molecular mechanism of curcumin-mediated SCs repair in order to improve the efficacy of curcumin in the clinical treatment of DPN. First, candidate target genes of curcumin in rat SC line RSC96 cells stimulated by high glucose were identified by RNA sequencing and bioinformatic analyses. Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out by Metascape, followed by 8 algorithms on Cytoscape to determine 4 hub genes, namly Hmox1, Pten, Vegfa and Myc. Next, gene set enrichment analysis (GSEA) and Pearson function showed that Hmox1 was significantly correlated with apoptosis. Subsequently, qRT-PCR, MTT assay, flow cytometry, caspase-3 activity detection and westernblot showed that curcumin treatment increased RSC96 cell viability, reduced cell apoptosis, increased Hmox1, Pten, Vegfa and Myc expression, and up-regulated Akt phosphorylation level under high glucose environment. Finally, molecular docking predicted the binding site of curcumin to Hmox1. These results suggest that curcumin can reduce the apoptosis of SCs induced by high glucose, and Hmox1 is a potential target for curcumin. Our findings provide new insights about the mechanism of action of curcumin on SC as a potential treatment in DPN.
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Biología Computacional , Curcumina , Neuropatías Diabéticas , Células de Schwann , Curcumina/farmacología , Animales , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/metabolismo , Ratas , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular , Simulación del Acoplamiento Molecular , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Glucosa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Supervivencia Celular/efectos de los fármacos , Fármacos Neuroprotectores/farmacologíaRESUMEN
Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1'-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation.
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Analgésicos , Epóxido Hidrolasas , Neuralgia , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/metabolismo , Animales , Neuralgia/tratamiento farmacológico , Masculino , Ratones , Analgésicos/farmacología , Analgésicos/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Urea/análogos & derivados , Urea/farmacología , Evaluación Preclínica de Medicamentos , Edema/tratamiento farmacológico , Ratas , Adamantano/análogos & derivados , Adamantano/farmacología , Adamantano/uso terapéuticoRESUMEN
Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized for their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying their neurotrophic impact on the peripheral nerve system (PNS) remains elusive. Our study delves into the neurotrophic effects of DPP-4 inhibitors, including Diprotin A, linagliptin, and sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), and Stromal cell-derived factor (SDF)-1a-known DPP-4 substrates with neurotrophic properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth in response to these agents. Remarkably, all DPP-4 inhibitors and PACAP demonstrated a significant elongation of neurite length in DRG neurons (PACAP 0.1 µM: 2221 ± 466 µm, control: 1379 ± 420, p < 0.0001), underscoring their potential in nerve regeneration. Conversely, NPY and SDF-1a failed to induce neurite elongation, accentuating the unique neurotrophic properties of DPP-4 inhibition and PACAP. Our findings suggest that the upregulation of PACAP, facilitated by DPP-4 inhibition, plays a pivotal role in promoting neurite elongation within the PNS, presenting a promising avenue for the development of novel DPN therapies with enhanced neurodegenerative capabilities.
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Neuropatías Diabéticas , Inhibidores de la Dipeptidil-Peptidasa IV , Ganglios Espinales , Proyección Neuronal , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Animales , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Proyección Neuronal/efectos de los fármacos , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/metabolismo , Ratones , Neuropéptido Y/metabolismo , Neuropéptido Y/farmacología , Quimiocina CXCL12/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Linagliptina/farmacología , Dipeptidil Peptidasa 4/metabolismo , Fosfato de Sitagliptina/farmacología , Células Cultivadas , Neuritas/efectos de los fármacos , Neuritas/metabolismo , OligopéptidosRESUMEN
Diabetic peripheral neuropathy (DPN) is a complication of diabetes mellitus that lacks specific treatment, its high prevalence and disabling neuropathic pain greatly affects patients' physical and mental health. Schwann cells (SCs) are the major glial cells of the peripheral nervous system, which play an important role in various inflammatory and metabolic neuropathies by providing nutritional support, wrapping axons and promoting repair and regeneration. Increasingly, high glucose (HG) has been found to promote the progression of DPN pathogenesis by targeting SCs death regulation, thus revealing the specific molecular process of programmed cell death (PCD) in which SCs are disrupted is an important link to gain insight into the pathogenesis of DPN. This paper is the first to review the recent progress of HG studies on apoptosis, autophagy, pyroptosis, ferroptosis and necroptosis pathways in SCs, and points out the crosstalk between various PCDs and the related therapeutic perspectives, with the aim of providing new perspectives for a deeper understanding of the mechanisms of DPN and the exploration of effective therapeutic targets.
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Neuropatías Diabéticas , Células de Schwann , Células de Schwann/metabolismo , Células de Schwann/patología , Humanos , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/patología , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/etiología , Animales , Apoptosis , Muerte Celular , Autofagia/fisiología , Necroptosis/fisiologíaRESUMEN
Diabetic neuropathy (DN) is a common complication of diabetes, affecting over 50% of patients, leading to significant pain and a burden. Currently, there are no effective treatments available. Cell death is considered a key factor in promoting the progression of DN. This article reviews how cell death is initiated in DN, emphasizing the critical roles of oxidative stress, mitochondrial dysfunction, inflammation, endoplasmic reticulum stress, and autophagy. Additionally, we thoroughly summarize the mechanisms of cell death that may be involved in the pathogenesis of DN, including apoptosis, autophagy, pyroptosis, and ferroptosis, among others, as well as potential therapeutic targets offered by these death mechanisms. This provides potential pathways for the prevention and treatment of diabetic neuropathy in the future.
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Muerte Celular , Neuropatías Diabéticas , Estrés Oxidativo , Humanos , Neuropatías Diabéticas/patología , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/etiología , Animales , Autofagia , Estrés del Retículo Endoplásmico , Apoptosis , Ferroptosis , Mitocondrias/metabolismo , Mitocondrias/patologíaRESUMEN
Anethole is a terpenoid with antioxidant, anti-inflammatory, and neuronal blockade effects, and the present work was undertaken to study the neuroprotective activity of anethole against diabetes mellitus (DM)-induced neuropathy. Streptozotocin-induced DM rats were used to investigate the effects of anethole treatment on morphological, electrophysiological, and biochemical alterations of the sciatic nerve (SN). Anethole partially prevented the mechanical hyposensitivity caused by DM and fully prevented the DM-induced decrease in the cross-sectional area of the SN. In relation to electrophysiological properties of SN fibers, DM reduced the frequency of occurrence of the 3rd component of the compound action potential (CAP) by 15%. It also significantly reduced the conduction velocity of the 1st and 2nd CAP components from 104.6 ± 3.47 and 39.8 ± 1.02 to 89.9 ± 3.03 and 35.4 ± 1.56 m/s, respectively, and increased the duration of the 2nd CAP component from 0.66 ± 0.04 to 0.82 ± 0.09 ms. DM also increases oxidative stress in the SN, altering values related to thiol, TBARS, SOD, and CAT activities. Anethole was capable of fully preventing all these DM electrophysiological and biochemical alterations in the nerve. Thus, the magnitude of the DM-induced neural effects seen in this work, and the prevention afforded by anethole treatment, place this compound in a very favorable position as a potential therapeutic agent for treating diabetic peripheral neuropathy.
Asunto(s)
Derivados de Alilbenceno , Anisoles , Diabetes Mellitus Experimental , Estrés Oxidativo , Nervio Ciático , Animales , Derivados de Alilbenceno/farmacología , Nervio Ciático/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas , Anisoles/farmacología , Anisoles/uso terapéutico , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/prevención & control , Neuropatías Diabéticas/metabolismo , Potenciales de Acción/efectos de los fármacos , Antioxidantes/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
BACKGROUND: Symptoms of autonomic neuropathy (AN) are common in patients with diabetes and advanced renal disease. As yet different domains of autonomic neuropathy cannot be detected by a singular laboratory or invasive test. COMPASS 31, a new self-assessment test, has shown reliable results not only in cardiac autonomic neuropathy but also in different sub-domains when judging manifestation of AN by scores. METHODS: One hundred eighty-three patients with or without diabetes were enrolled, one hundred nineteen of them were treated with permanent dialysis therapy (HD), sixty-four patients served as controls (eGFR > 60 ml/min.) Using COMPASS 31 different symptoms of AN were assessed (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes) and transferred into AN-scores. RESULTS: AN was more pronounced in dialysis patients compared with controls (AN-score 27,5 vs. 10,0; p < 0,01). These differences were present also in every sub-domain of AN (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes; p < 0,05 for all sub-domains). In diabetic patients there was a strong correlation between symptoms of AN and diabetes duration (correlation coefficient r = 0,45, p < 0,001). Current glycemic control (HbA1c), body mass index (BMI), sex, and height had no influence on AN when comparing dialysis patients and controls. C-reactive protein (CRP) showed a positive linear correlation with AN-scores (correlation coefficient r = 0,21; p < 0,05). CONCLUSION: Symptoms of AN are more pronounced in dialysis patients not only in total but also in all different domains of neuropathic changes. Longlasting diabetic disease promotes development of AN, as duration of diabetes was positively correlated with AN. Future longitudinal studies might help to identify the high cardiovascular and mortality risk in dialysis patients by the easy-to-use COMPASS 31 without need of invasive and time-spending methods for diagnosing AN.