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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
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
Diabetic Peripheral Neuropathy (DPN) is a prevalent and debilitating complication of diabetes, affecting a significant proportion of the diabetic population. Neuromodulation, an emerging therapeutic approach, has shown promise in the management of DPN symptoms. This systematic review aims to synthesize and analyze the current advancements in neuromodulation techniques for the treatment of DPN utilizing studies with preclinical animal models. A comprehensive search was conducted across multiple databases, including PubMed, Scopus, and Web of Science. Inclusion criteria were focused on studies utilizing preclinical animal models for DPN that investigated the efficacy of various neuromodulation techniques, such as spinal cord stimulation, transcranial magnetic stimulation, and peripheral nerve stimulation. The findings suggest that neuromodulation significantly alleviated pain symptoms associated with DPN. Moreover, some studies reported improvements in nerve conduction velocity and reduction in nerve damage. The mechanisms underlying these effects appeared to involve modulation of pain pathways and enhancement of neurotrophic factors. However, the review also highlights the variability in methodology and stimulation parameters across studies, highlighting the need for standardization in future research. Additionally, while the results are promising, the translation of these findings from animal models to human clinical practice requires careful consideration. This review concludes that neuromodulation presents a potentially effective therapeutic strategy for DPN, but further research is necessary to optimize protocols and understand the underlying molecular mechanisms. It also emphasizes the importance of bridging the gap between preclinical findings and clinical applications to improve the management of DPN in diabetic patients.
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Neuropatías Diabéticas , Modelos Animales de Enfermedad , Investigación Biomédica Traslacional , Animales , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/fisiopatología , Humanos , Estimulación de la Médula Espinal/métodos , Estimulación Magnética Transcraneal/métodosRESUMEN
BACKGROUND: Cardiac autonomic neuropathy (CAN) in diabetes mellitus (DM) is independently associated with cardiovascular (CV) events and CV death. Diagnosis of this complication of DM is time-consuming and not routinely performed in the clinical practice, in contrast to fundus retinal imaging which is accessible and routinely performed. Whether artificial intelligence (AI) utilizing retinal images collected through diabetic eye screening can provide an efficient diagnostic method for CAN is unknown. METHODS: This was a single center, observational study in a cohort of patients with DM as a part of the Cardiovascular Disease in Patients with Diabetes: The Silesia Diabetes-Heart Project (NCT05626413). To diagnose CAN, we used standard CV autonomic reflex tests. In this analysis we implemented AI-based deep learning techniques with non-mydriatic 5-field color fundus imaging to identify patients with CAN. Two experiments have been developed utilizing Multiple Instance Learning and primarily ResNet 18 as the backbone network. Models underwent training and validation prior to testing on an unseen image set. RESULTS: In an analysis of 2275 retinal images from 229 patients, the ResNet 18 backbone model demonstrated robust diagnostic capabilities in the binary classification of CAN, correctly identifying 93% of CAN cases and 89% of non-CAN cases within the test set. The model achieved an area under the receiver operating characteristic curve (AUCROC) of 0.87 (95% CI 0.74-0.97). For distinguishing between definite or severe stages of CAN (dsCAN), the ResNet 18 model accurately classified 78% of dsCAN cases and 93% of cases without dsCAN, with an AUCROC of 0.94 (95% CI 0.86-1.00). An alternate backbone model, ResWide 50, showed enhanced sensitivity at 89% for dsCAN, but with a marginally lower AUCROC of 0.91 (95% CI 0.73-1.00). CONCLUSIONS: AI-based algorithms utilising retinal images can differentiate with high accuracy patients with CAN. AI analysis of fundus images to detect CAN may be implemented in routine clinical practice to identify patients at the highest CV risk. TRIAL REGISTRATION: This is a part of the Silesia Diabetes-Heart Project (Clinical-Trials.gov Identifier: NCT05626413).
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Aprendizaje Profundo , Neuropatías Diabéticas , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico por imagen , Neuropatías Diabéticas/etiología , Reproducibilidad de los Resultados , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/epidemiología , Interpretación de Imagen Asistida por Computador , Sistema Nervioso Autónomo/fisiopatología , Sistema Nervioso Autónomo/diagnóstico por imagen , Fondo de Ojo , Cardiopatías/diagnóstico por imagen , Cardiopatías/diagnóstico , Adulto , Inteligencia ArtificialRESUMEN
Diabetic peripheral neuropathy (DPN) is a prevalent complication of chronic diabetes mellitus and has a significant impact on quality of life. DPN typically manifests itself as a symmetrical, length-dependent sensorimotor polyneuropathy with severe effects on gait. Surface electromyography (sEMG) is a valuable low-cost tool for assessing muscle activation patterns and precise identification of abnormalities. For the present study, we used information theory methods, such as cross-correlation (CC), normalized mutual information (NMI), conditional granger causality (CG-Causality), and transfer entropy (TE), to evaluate muscle network connectivity in three population groups: 33 controls (healthy volunteers, CT), 10 diabetic patients with a low risk of DPN (LW), and 17 moderate/high risk patients (MH). The results obtained indicated significant alterations in the intermuscular coupling mechanisms due to diabetes and DPN, with the TE group showing the best performance in detecting differences. The data revealed a significant increase in information transfer and muscle connectivity in the LW group over the CT group, while the MH group obtained significantly lower values for these metrics than the other two groups. These findings highlight the sEMG coupling metrics' potential to reveal neuromuscular mechanisms that could aid the development of targeted rehabilitation strategies and help monitor DPN patients.
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Neuropatías Diabéticas , Electromiografía , Humanos , Neuropatías Diabéticas/fisiopatología , Electromiografía/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Músculo Esquelético/fisiopatología , AncianoRESUMEN
Diabetes, commonly known for its metabolic effects, also critically affects the enteric nervous system (ENS), which is essential in regulating gastrointestinal (GI) motility, secretion, and absorption. The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions, such as gastroparesis and irregular bowel habits, primarily due to disruptions in the function of neuronal and glial cells within the ENS, as well as oxidative stress and inflammation. This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients. Additionally, it discusses the latest advances in diagnostic approaches, emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals. The editorial also reviews current and emerging therapeutic strategies, focusing on pharmacological treatments, dietary management, and potential neuromodulatory interventions. Ultimately, this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes, aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.
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Neuropatías Diabéticas , Sistema Nervioso Entérico , Motilidad Gastrointestinal , Humanos , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Sistema Nervioso Entérico/fisiopatología , Enfermedades Gastrointestinales/fisiopatología , Enfermedades Gastrointestinales/terapia , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Tracto Gastrointestinal/inervación , Tracto Gastrointestinal/fisiopatología , Gastroparesia/terapia , Gastroparesia/fisiopatología , Gastroparesia/diagnóstico , Gastroparesia/etiología , Estrés Oxidativo , Calidad de VidaRESUMEN
BACKGROUND: Diabetic polyneuropathy (DPN) is a notable microvascular complication of DM, affecting 16%-66% globally. DPN often leads to proprioceptive deficits in the lower limbs (LL), leading to impaired functional performance. However, evidence supporting proprioceptive rehabilitation programs (PRP) for DPN remains scarce. AIMS: This pilot study aims to evaluate the effectiveness of a novel 12-week PRP on LL static and dynamic proprioception and shed light on the potential benefits of PRP for DPN population. METHODS: Randomized Controlled Trail was conducted among 30 DPN patients (age 53.25±7.72 years, BMI 24.01±1.41 and DM duration 9.48±6.45 years), randomly allocated to intervention (n = 15) or control (n = 15) groups. The intervention group received PRP 3 times/week for 12 weeks. The control group received no exercise. Both groups received regular diabetic care. Static and dynamic proprioception of both LL were assessed at baseline, 6 weeks and 12 weeks. Position-reposition test was used to assess ankle joint position sense by obtaining difference between target and reproduced angles. Error in detecting knee angle and speed were obtained by performing Lower Limb Matching and Sense of Movement tests respectively to assess dynamic proprioception. RESULTS: Two-way ANOVA and paired comparisons revealed, no significant improvement in proprioceptive deficits at 6 weeks (p>0.05), but significant improvement was achieved at 12-weeks (p<0.05) in the intervention group. Mean errors in Pposition re-position(R:p<0.001, L;p<0.001) and Lower limb matching (R:p<0.001, L;p<0.001) tests reduced by 5° and 10° respectively, indicating a70% improvement in the intervention group. Error of detecting speed reduced only on right side by 0.041ms-1 accounting for a 42% improvement. No improvements were observed in the control group. CONCLUSIONS: Novel 12-week PRP may yield a significant reduction in LL proprioceptive deficits among DPN patients. Future RCTs with larger samples should compare the effectiveness of this PRP compared with conventional rehabilitation programs.
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Neuropatías Diabéticas , Propiocepción , Humanos , Persona de Mediana Edad , Neuropatías Diabéticas/rehabilitación , Neuropatías Diabéticas/fisiopatología , Masculino , Proyectos Piloto , Femenino , Propiocepción/fisiología , Adulto , Resultado del TratamientoRESUMEN
INTRODUCTION: LX-9211 is a drug designed to treat neuropathic pain conditions. It functions by inhibiting the adaptor-associated kinase 1 (AAK1) enzyme which promotes clathrin-dependent endocytosis. Preclinical studies have shown that LX-9211 does produce a reduction in nociceptive related behaviors and produces no major adverse effects in rats. Thus, LX-9211 has advanced to clinical trials to assess its safety and efficacy in humans. So far, phase 1 and phase 2 clinical trials involving patients with postherpetic neuralgia and diabetic peripheral neuropathic pain have been conducted with phase 3 trials planned in the future. AREAS COVERED: This paper highlights preclinical studies involving LX-9211 in rodents. Additionally, phase 1 clinical trials examining the safety of LX-9211 in healthy subjects as well as phase 2 studies looking at the safety and efficacy of LX-9211 compared to placebo in patients with diabetic peripheral neuropathic pain and postherpetic neuralgia are also discussed. EXPERT OPINION: In phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety.
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Neuropatías Diabéticas , Neuralgia Posherpética , Neuralgia , Humanos , Animales , Neuralgia/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/fisiopatología , Neuralgia Posherpética/tratamiento farmacológico , Ratas , Analgésicos/farmacología , Analgésicos/efectos adversosRESUMEN
This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM). METHODS: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM. RESULTS: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN. CONCLUSION: The review presents a possible relationship between DPN and CAN, such as in their severity.
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Enfermedades del Sistema Nervioso Autónomo , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Cardiomiopatías Diabéticas/epidemiología , Cardiomiopatías Diabéticas/complicaciones , Cardiomiopatías Diabéticas/diagnóstico , Sistema Nervioso Autónomo/fisiopatología , Factores de RiesgoRESUMEN
Aim and objectives: Visual dysfunction in diabetes mellitus (DM) is multifactorial and can be due to vascular disease, and metabolic abnormalities that can affect the retina, optic nerve, and visual pathways. Visual evoked potential (VEP) is an electrophysiological test that can quantify the functional integrity of the visual pathways from the retina via the optic nerves, and optic tracts to the visual cortices. In this study, we aimed to investigate the visual pathway dysfunction among diabetics without retinopathy compared with healthy controls and to look for any correlation with diabetic neuropathy, duration of diabetes, or HbA1c level. Methods: The study included 75 diabetic patients and 75 age and sex-matched controls. VEPs were recorded using the pattern reversal stimulation method on the Medtronic EMG EP machine, and P100 latency and N75-P100 amplitude were recorded in both diabetic patients and healthy controls. Results: Mean P100 latency was significantly prolonged and N75-P100 amplitude significantly reduced among diabetic cases compared to healthy controls (p < 0.001). Among diabetics with peripheral neuropathy, P100 latency was significantly prolonged and N75-P100 amplitude was significantly reduced compared to diabetics without peripheral neuropathy. A significant positive correlation of VEP P100 latency (p < 0.001) and a negative correlation with N75-P100 amplitude (p < 0.001) with duration of disease were also found. Conclusion: VEP changes are observed in diabetics before the development of retinopathy or peripheral neuropathy indicating optic pathway dysfunction, which precedes the development of these complications. Early preclinical visual pathway dysfunction can warrant taking the necessary measures to reduce diabetic complications. Abbreviations: DM = Diabetes Mellitus, VEP = Visual Evoked Potential, HbA1c = Hemoglobin A1 c, MRI = Magnetic Resonance Imaging, EEG = Electroencephalography, P100 = Positive wave peak at latency 100 ms (millisecond), N75 = Negative wave peak at latency 75 ms (millisecond), N145 = Negative wave peak at latency 145 ms (millisecond), OCT = Optical coherence tomography, PRVEP = Pattern Reversal Visual Evoked Potential, NCS = Nerve Conduction Study, SSR = Sympathetic Skin Response, IL1 = Interleukin-1, LIF = Leukemia inhibitory factor, CNTF = Ciliary neurotrophic factor, TNF alpha = Tumor necrosis factor-alpha, TGF-beta = Transforming growth factor-beta.
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Neuropatías Diabéticas , Retinopatía Diabética , Potenciales Evocados Visuales , Vías Visuales , Humanos , Potenciales Evocados Visuales/fisiología , Masculino , Femenino , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/etiología , Persona de Mediana Edad , Retinopatía Diabética/fisiopatología , Retinopatía Diabética/diagnóstico , Vías Visuales/fisiopatología , Adulto , Agudeza VisualRESUMEN
OBJECTIVES: To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of Δheart rate (HR)/Δsystolic blood pressure (SBP), index of cardiac baroreflex function, in identifying neurogenic OH. METHODS: In 208 participants with T2D, we diagnosed early cardiovascular autonomic neuropathy (CAN) and confirmed CAN according to 1 and 2 HR-based cardiovascular reflex tests (HR-CARTs). Through OH test we defined OH as SBP falls of ≥20 and ≥30 mm Hg with supine SBPs of <140 and ≥140 mm Hg, respectively. In participants with OH, we used the lying-to-standing and OH test and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN). RESULTS: OH was present in 25 participants and associated with lower HR-CART scores, higher glycosylated hemoglobin level, the presence of CAN, retinopathy, and peripheral vascular disease, the absence of hypertension, and physical activity (all, P < .05) but not with interfering drugs and ß-blockers. In a multiple logistic regression, HR-CAN was the main determinant of OH (odds ratio, 4.74) with physical activity and hypertension (odds ratios, 0.16 and 0.23; R2 = 0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (area under the receiver operating characteristic curve, 0.816 ± 0.087) and, at the cutoff of 0.5 bpm/mm Hg, a sensitivity of 100% and specificity of 63.2%. CONCLUSION: CAN remains the primary determinant of OH in T2D but does not explain all its variance. The index ΔHR/ΔSBP may represent a useful clinical tool to identify neurogenic OH.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Frecuencia Cardíaca , Hipotensión Ortostática , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/fisiopatología , Hipotensión Ortostática/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Frecuencia Cardíaca/fisiología , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiologíaRESUMEN
Altered functional connectivity has been demonstrated in key brain regions involved in pain processing in painful diabetic peripheral neuropathy. However, the impact of neuropathic pain treatment on functional connectivity does not appear to have been investigated. Sixteen participants underwent resting state functional MRI when optimally treated for neuropathic pain during their involvement in the Optimal Pathway for Treating Neuropathic Pain in Diabetes Mellitus trial and 1 week following withdrawal of treatment. On discontinuation of pain treatment, there was an increase in functional connectivity between the left thalamus and primary somatosensory cortex (S1) and the left thalamus and insular cortex, key brain regions that are involved in cerebral processing of pain. The changes in functional connectivity between scans also correlated with measures of pain (baseline pain severity and Neuropathic Pain Symptom Inventory). Moreover, when participants were stratified into higher- and lower-than-average baseline pain subgroups, the change in thalamic-S1 cortical functional connectivity between scans was significantly greater in those with high baseline pain compared with the lower-baseline-pain group. This study shows that thalamo-cortical functional connectivity has the potential to act as an objective biomarker for neuropathic pain in diabetes for use in clinical pain trials.
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Neuropatías Diabéticas , Imagen por Resonancia Magnética , Neuralgia , Tálamo , Humanos , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico por imagen , Masculino , Tálamo/fisiopatología , Tálamo/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Neuralgia/fisiopatología , Corteza Somatosensorial/fisiopatología , Corteza Somatosensorial/diagnóstico por imagen , Anciano , Privación de Tratamiento , Adulto , Corteza Insular/diagnóstico por imagen , Corteza Insular/fisiopatologíaRESUMEN
Objective: To test the new method of iMAX (the minimum stimulus current that elicits the maximum compound muscle action potential amplitude) electrodiagnosis, verify the feasibility of this method in evaluating the excitability of peripheral motor axons, and preliminarily explore the clinical application value. Methods: This study was a cross-sectional study. A total of 50 healthy subjects were recruited from the outpatient department of Peking University Third Hospital from June 2022 to March 2023, including 25 males and 25 females, aged 25-68 (48±8) years. Eleven patients with Charcot-Marie-Pain-1A (CMT1A), 7 males and 4 females, aged 19-55 (41±13) years and 21 patients with diabetic peripheral neuropathy (DPN), 10 males and 11 females, aged 28-79 (53±16) years were enrolled in this study. iMAX of bilateral median nerves, ulnar nerves and peroneal nerves were detected in all patients. Repeatable motor responses with minimum motor threshold and amplitude of at least 0.1 mV and the minimum stimulus current intensity, at which the maximum compound muscle action potential amplitude is elicited, were measured respectively [1 mA increment is called (iUP) and, 0.1 mA adjustment is called (iMAX)].Comparison of the parameters: the parameters of threshold, iUP and iMAX were compared among different age groups, genders and sides, body mass index(BMI) values and detection time , as well as between CMT1A patients, DPN patients and healthy subjects. Results: In healthy subjects, the threshold, iUP value and iMAX value were (1.8±0.7) mA, (4.4±1.2) mA, and (4.2±1.3) mA respectively; ulnar nerve (3.1±1.6) mA, (6.8±3.2) mA, (6.4±3.2) mA; peroneal nerve (3.7±2.0) mA, (7.8±2.8) mA, (7.4±2.9) mA. There were statistically significant differences in threshold, iUP value and iMAX value among different age groups (all P<0.001).With the increase of age, there was a trend of increasing threshold, iUP, and iMAX values in different nerves, and the differences are statistically significant (all P<0.001). There were no significant differences in gender, side and detection time threshold, iUP value and iMAX value (all P>0.05). The parameters of healthy subjects with high BMI value were higher than those of healthy subjects with low BMI value(all P<0.05). Compared with the healthy subjects, the parameters of 11 CMT1A patients were significantly increased (all P<0.05), and the parameters of 21 DPN patients were slightly increased (P<0.05). Conclusion: The new iMAX method reflects the excitability of motor axons and early axonal dysfunction, which is an important supplement to the traditional nerve conduction, and can be used to monitor motor axon excitability disorders.
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Potenciales de Acción , Electrodiagnóstico , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Transversales , Anciano , Electrodiagnóstico/métodos , Neuronas Motoras/fisiología , Nervio Mediano/fisiopatología , Conducción Nerviosa , Nervio Cubital , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Nervios Periféricos/fisiopatología , Estimulación Eléctrica , ElectromiografíaRESUMEN
The early diagnosis of diabetic neuropathy (DN) is fundamental in order to enact timely therapeutic strategies for limiting disease progression. In this work, we explored the suitability of standing balance task for identifying the presence of DN. Further, we proposed two diagnosis pathways in order to succeed in distinguishing between different stages of the disease. We considered a cohort of non-neuropathic (NN), asymptomatic neuropathic (AN), and symptomatic neuropathic (SN) diabetic patients. From the center of pressure (COP), a series of features belonging to different description domains were extracted. In order to exploit the whole information retrievable from COP, a majority voting ensemble was applied to the output of classifiers trained separately on different COP components. The ensemble of kNN classifiers provided over 86% accuracy for the first diagnosis pathway, made by a 3-class classification task for distinguishing between NN, AN, and SN patients. The second pathway offered higher performances, with over 97% accuracy in identifying patients with symptomatic and asymptomatic neuropathy. Notably, in the last case, no asymptomatic patient went undetected. This work showed that properly leveraging all the information that can be mined from COP trajectory recorded during standing balance is effective for achieving reliable DN identification. This work is a step toward a clinical tool for neuropathy diagnosis, also in the early stages of the disease.
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Algoritmos , Neuropatías Diabéticas , Diagnóstico por Computador , Equilibrio Postural , Humanos , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Equilibrio Postural/fisiología , Masculino , Femenino , Persona de Mediana Edad , Diagnóstico por Computador/métodos , Anciano , Reproducibilidad de los Resultados , Posición de Pie , AdultoRESUMEN
INTRODUCTION: Diabetic neuropathy is frequently underdiagnosed and undertreated. Logistic problems accompany the routine use of the biothesiometer. Hence, we attempted to find a more easily available alternative. RESEARCH DESIGN AND METHODS: 149 patients with diabetes visiting the outpatient endocrinology clinic were assessed for vibration sense using a 128-Hz tuning fork (absolute timing method) and a biothesiometer. A reading of >25 V on the biothesiometer (known as vibration perception threshold or VPT) was taken as the diagnostic criterion for severe neuropathy while >15 V was used as an indicator of the mild form. The sensitivity and specificity were calculated by constructing the receiver operating characteristic curve (ROC). A p value of <0.05 was considered as statistically significant. RESULTS: The timed tuning fork (TTF) test showed a statistically significant correlation with the VPT measurements (r=-0.5, p=0.000). Using the VPT findings as a reference, a timed tuning fork cut-off of 4.8 s was 76% sensitive and 77% specific in diagnosing mild neuropathy while absent tuning fork sensation demonstrated 70% sensitivity and 90% specificity in detecting severe neuropathy. CONCLUSIONS: The tuning fork test demonstrated significant sensitivity and specificity in diagnosing diabetic peripheral neuropathy when compared against the biothesiometer. A cut-off of 4.8 s can be a useful indicator of the early stages of onset of the condition.
Asunto(s)
Neuropatías Diabéticas , Sensibilidad y Especificidad , Umbral Sensorial , Centros de Atención Terciaria , Vibración , Humanos , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Estudios Transversales , India , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano , Curva ROC , Tamizaje Masivo/métodos , Tamizaje Masivo/instrumentaciónRESUMEN
BACKGROUND Diabetes-related foot disease (DFD) is a serious complication of diabetes, increasing the risk of amputation. Coimplications are preventable, but most diabetics do not receive proper screening and treatment, despite indications. This study was a pilot screening of diabetes-related foot disease in a group of people with glycemic disorders. MATERIAL AND METHODS We recruited 143 volunteers over 40 years of age. In the final analysis, we included 85 people diagnosed with glycemic disorders (diabetes or prediabetes), for whom we performed a total of 170 foot measurements. We screened for peripheral artery disease using: foot pulse, ankle-brachial index (manual and automatic), toe-brachial index, and transcutaneous oxygen pressure (TcPO2). To screen for diabetic peripheral neuropathy, we used indicators of loss of protective sensation: pressure perception and temperature perception, and plantar pressure distribution. RESULTS A history of diabetes was reported by 26 (30.6%) of the subjects. Disorders of at least 1 foot occurred in 20 (66.7%) subjects with diagnosed diabetes and in 10 (17%) subjects declaring no diabetes. Higher risk and DFD category were correlated with duration of diabetes (r=0.68, p=0.007), glycemic levels (r=0.56, p=0.001), age (r=0.57, p=0.007), and the presence of other diabetes complications. The best predictor of risk in DFD was manual ABI, p=0.001; followed by automatic ABI, p=0.006. CONCLUSIONS Our results showed that peripheral complications of diabetes, such as DFD, often remain undiagnosed and untreated despite the high risk of developing ulcers. There is a need for multi-center screening studies.
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Pie Diabético , Humanos , Proyectos Piloto , Pie Diabético/diagnóstico , Pie Diabético/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Índice Tobillo Braquial , Factores de Riesgo , Diabetes Mellitus Tipo 2/complicaciones , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/complicaciones , Estado Prediabético/complicaciones , Estado Prediabético/fisiopatología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/etiología , Pie/fisiopatologíaRESUMEN
BACKGROUND: Diabetes Mellitus (DM) is known to induce a wide range of harmful effects on several organs, notably leading to ineffective esophageal motility (IEM). However, the relationship between DM and IEM is not fully elucidated. We aimed to determine the relationship between DM and IEM and to evaluate the impact of DM's end organ complications on IEM severity. METHODS: A multicenter cohort study of consecutive patients undergoing high-resolution esophageal manometry (HREM) was performed. We reviewed medical records of patients diagnosed with IEM using HREM, encompassing data on demographics, DM history, antidiabetic and other medications as well as comorbidities. KEY RESULTS: Two hundred and forty six subjects met the inclusion criteria. There was no significant difference in any of the HREM parameters between diabetics and nondiabetics. Out of 246 patients, 92 were diabetics. Diabetics with neuropathy presented a significantly lower distal contractile integral (DCI) value compared to those without neuropathy (248.2 ± 226.7 mmHg·cm·sec vs. 375.6 ± 232.4 mmHg·cm·sec; p = 0.02) Similarly, the DCI was lower in diabetics with retinopathy compared to those without retinopathy (199.9 ± 123.1 mmHg·cm·sec vs. 335.4 ± 251.7 mmHg·cm·sec; p = 0.041). Additionally, a significant difference was observed in DCI values among DM patients with ≥2 comorbidities compared to those without comorbidities (224.8 ± 161.0 mmHg·cm·sec vs. 394.2 ± 243.6 mmHg·cm·sec; p = 0.025). Around 12.6% of the variation in DCI could be explained by its linear relationship with hemoglobin A1c (HbA1c), with a regression coefficient (ß) of -55.3. CONCLUSION & INFERENCES: DM is significantly associated with IEM in patients with neuropathy, retinopathy, or multiple comorbidities. These results are pivotal for tailoring patient-specific management approaches.
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Complicaciones de la Diabetes , Trastornos de la Motilidad Esofágica , Manometría , Humanos , Trastornos de la Motilidad Esofágica/fisiopatología , Trastornos de la Motilidad Esofágica/epidemiología , Trastornos de la Motilidad Esofágica/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/fisiopatología , Estudios de Cohortes , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/epidemiología , Diabetes Mellitus/epidemiología , Adulto , Estudios RetrospectivosRESUMEN
BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.