Vitaminas B neurotrópicas y neuropatía periférica: estado del arte y acuerdo de expertos

Propósito: La neuropatía periférica tiene un espectro clínico inespecífico y multifactorial, con frecuente subdiagnóstico y terapéutica de eficacia variable. Existe una heterogénea prescripción de vitaminas B, las cuales pueden desempeñar un rol importante en el manejo de diferentes neuropatías; sin embargo, en Colombia no existen guías clínicas al respecto. El propósito de este trabajo es orientar en el reconocimiento temprano de las neuropatías periféricas y generar recomendaciones sobre el uso adecuado de vitaminas B neurotrópicas. Descripción de la metodología: Acuerdo de expertos sobre la neuropatía periférica y el rol terapéutico de las vitaminas B con énfasis en la epidemiología en Colombia, diagnóstico y tratamiento. Contenidos: En Colombia, la prevalencia de neuropatía periférica se estima cercana al 10 %, sin embargo, no hay datos recientes. Dentro de las etiologías más frecuentes se encuentran la neuropatía diabética, infecciosa, inflamatoria, carenciales, toxica y farmacológica. Se recomiendan las siguientes herramientas de tamizaje en población de riesgo: DN4, MNSI, test de monofilamento, test de vibración y valoración de reflejos. Las vitaminas B1, B6 y B12 son seguras, accesibles y pueden ser eficaces en neuropatía periférica, incluso cuando el déficit no ha sido demostrado, pero con requerimientos particulares en su administración conjunta. Conclusiones: Las neuropatías periféricas son un reto diagnóstico y terapéutico que requiere la identificación oportuna para el tratamiento de la etiología subyacente y el control de síntomas. El uso de vitaminas B neurotrópicas es efectivo y seguro en neuropatía periférica carencial, y también parece ser eficaz en el manejo de neuropatías periféricas de diferentes etiologías.

Purpose: Peripheral neuropathy has a nonspecific and multifactorial clinical spectrum, with frequent underdiagnosis and therapeutics of variable efficacy. There is a high but heterogeneous prescription of B vitamins, which can play an important role in the management of different neuropathies; however, in Colombia there are no clinical guidelines in this regard. The purpose of this article is to guide the early recognition of peripheral neuropathy and generate recommendations on the proper use of neurotropic B vitamins. Description of the methodology: Expert agreement on peripheral neuropathy and the therapeutic role of B vitamins with emphasis on epidemiology in Colombia, diagnosis and treatment. Contents: In Colombia, there are no recent data to estimate the prevalence of peripheral neuropathy; the main etiologies are: diabetes mellitus, nutritional deficiencies, herpes zoster and neuropathies due to chemotherapy. Given risk factors in the anamnesis, the use of DN4, MNSI, monofilament test, vibration test and assessment of reflexes is recommended. Vitamins B1, B6, and B12 are safe and can be effective in peripheral neuropathy, even when the deficit has not been demonstrated, but with special requirements in their joint administration. Conclusions: peripheral neuropathies are a diagnostic and therapeutic challenge, and require timely identification, for the treatment of the underlying etiology and symptom control. The use of neurotropic B vitamins is effective and safe in deficient peripheral neuropathy, and also appears to be effective in the management of peripheral neuropathies of different etiologies.

Neuropatía Diabética: Una revisión narrativa de fisiopatología, diagnóstico y tratamiento

La neuropatía diabética se presenta hasta en el 60 % de los pacientes diabéticos. La neuropatía diabética periférica es la causa más común de neuropatía en el mundo. La fisiopatología de la neuropatía diabética involucra daño periférico nervioso por acumulación de productos tóxicos derivados de la hiperglicemia. El sistema nervioso central se ve posteriormente involucrado a través de sensibilización, disminución de la función del sistema inhibitorio y aumento en la excitabilidad del sistema de facilitación. La clínica más común se manifiesta de manera simétrica afectando fibras sensitivas pequeñas y grandes, aunque se han encontrado formas atípicas de presentación. Las pruebas diagnósticas confirmatorias se reservan para la duda diagnóstica, casos de síntomas atípicos o investigación. El consenso en cuanto a tratamiento es el uso de gabapentinoides, antidepresivos tricíclicos e inhibidores de recaptura de serotonina y noradrenalina. Estas tres familias se consideran como primera línea de tratamiento.

Diabetic neuropathy occurs in up to 60% of diabetic patients. Diabetic peripheral neuropathy is the most common cause of neuropathy in the world. The pathophysiology of diabetic neuropathy involves peripheral nerve damage due to the accumulation of toxic products derived from hyperglycemia. The central nervous system is subsequently involved through sensitization, decreased function of the inhibitory system, and increased excitability of the facilitative system. The most common symptoms manifest symmetrically, affecting small and large sensory fibers, although atypical forms of presentation have been found. Confirmatory diagnostic tests are reserved for diagnostic doubt, atypical symptoms, or research. The consensus regarding treatment is the prescription of gabapentinoids, tricyclic antidepressants, and serotonin and norepinephrine reuptake inhibitors. These three families are considered the first line.

Perfil clínico-metabólico de pacientes pé diabéticos frequentadores de uma Unidade Básica de Saúde de Altamira, Pará, Brasil / Clinical-metabolic profile of diabetic foot patients attendinga Basic Health Unit in Altamira, Pará, Brazil

Introdução: o pé diabético é de origem neuropática e representa uma das complicações do diabetes mellitus, abrange várias condições patológicas, que incluem neuropatia, doença arterial periférica, neuroartropatia de Charcot, ulceração do pé e, em alguns casos, amputação. Objetivo: descrever o perfil clínico-metabólico de pacientes pé diabéticos frequentadores de uma Unidade Básica de Saúde (UBS). Material e Método: trata-se de um estudo descritivo exploratório com abordagem quantitativa. Foram avaliados 15 pacientes portadores de úlceras do pé diabético atendidos em uma Unidade Básica de Saúde de Altamira, estado do Pará, Brasil. Os dados foram submetidos à análise de acordo com os indicadores dos perfis investigados. Resultados: todos os pacientes possuem diabetes tipo II, baixos níveis de renda familiar e escolaridade. O Índice de Massa Corpórea (IMC) foi de 92%, circunferência abdominal 93%, proteína C reativa ultrassensível, interleucina-6 e hemoglobina glicada estavam superiores ao normal em mais da metade dos doentes, assim como a vitamina D estava deficiente em mais da metade dos pacientes. Conclusões: há barreiras ao manejo adequado dos portadores de pé diabético na atenção básica da cidade de Altamira que podem contribuir para o desenvolvimento de complicações macro e microvasculares. Recomendações técnicas direcionadas aos gestores locais contribuem para a atenção básica na região.

Introduction: the diabetic foot is of neuropathic origin and represents one of the complications of diabetes mellitus, encompasses several pathological conditions, including neuropathy, peripheral arterial disease, Charcot neuroarthropathy, foot ulceration, osteomyelitis and, in some cases, amputation. Objective: to describe the clinical-metabolic profile of diabetic foot patients attending a Basic Health Unit (BHU). Material and Method: this is a descriptive exploratory study with a quantitative approach. Fifteen patients with diabetic foot ulcers treated at the Basic Health Unit in Altamira, state of Pará, Brazil, were evaluated. The data were submitted to analysis according to the indicators of the investigated profiles. Results: all patients have Type 2 Diabetes, low level of family income and education. The Body Mass Index (BMI) was 92%, abdominal circumference (93%), Ultrasensitive C-Reactive Protein, Interleukin-6 and glycated hemoglobin were higher than normal in more than half of the patients, as well as vitamin D was deficient in more of half of the patients. Conclusions: there are barriers to the proper management of patients with diabetic foot in primary care in the city of Altamira that can contribute to the development of macro and microvascular complications. Technical recommendations directed at local managers contribute to primary care in the region.

Oscilações no equilíbrio estático relacionadas a diabetes mellitus tipo 2 ­ uma revisão sistemática / Oscillations in static balance related to type 2 diabetes mellitus ­ a systematic review

INTRODUÇÃO: A diabetes mellitus tipo 2 (DM2) é uma doença crônica sistêmica ligada às mudanças no estilo de vida, fatores genéticos e ambientais, ocasionando complicações como a neuropatia diabética periférica (NDP). Além disso, pessoas com DM2 apresentam um retardo na condução nervosa das vias motoras e sensoriais, podendo levar a alterações no equilíbrio. OBJETIVO: Descrever as alterações de equilíbrio estático em pacientes com DM2. MATERIAIS E MÉTODOS: A revisão sistemática iniciou em outubro de 2021 ocorrendo a última busca em março de 2023, os artigos foram selecionados por dois autores de forma independente nas bases de dados Pubmed, Scopus e Web of Science. Seguindo o protocolo registrado no PROSPERO e descrito com base nas recomendações do PRISMA, foram selecionados estudos observacionais sem restrição a ano de publicação e idioma, envolvendo equilíbrio de DM em qualquer idade. RESULTADOS: Foram eleitos 20 artigos com indivíduos DM e NPD em um total de 1564 voluntários, demonstrando: DM causa mudança na velocidade e deslocamento do COP alterando o equilíbrio estático, a presença da NPD piora a estabilidade corporal devido as alterações sensitivo motoras. CONCLUSÃO: Indivíduos com DM e NPD demonstram alterações na estabilidade postural como velocidade e deslocamento do centro de pressão (COP) para as direções AP e ML, com ou sem informação visual e na presença da NPD.

INTRODUCTION: Type 2 diabetes mellitus (DM2) is a chronic systemic disease linked to changes in lifestyle, genetic and environmental factors, causing complications such as peripheral diabetic neuropathy (PDN). In addition, people with DM2 have a delay in nerve conduction in motor and sensory pathways, which can lead to changes in balance. OBJECTIVE: To describe static balance changes in patients with DM2. MATERIALS AND METHODS: The systematic review started in October 2021 with the last search occurring in March 2023, the articles were selected by two authors independently from the Pubmed, Scopus and Web of Science databases. Following the protocol registered in PROSPERO and described based on the PRISMA recommendations, observational studies were selected without restriction on year of publication and language, involving DM balance at any age. RESULTS: 20 articles were chosen with DM and NPD individuals in a total of 1564 volunteers, demonstrating that DM causes changes in the speed and displacement of the COP, altering the static balance and the presence of NPD worsens body stability due to sensory-motor changes. CONCLUSION: Individuals with DM and NPD demonstrate changes in postural stability such as velocity and displacement of the center of pressure (COP) for the AP and ML directions, with or without visual information and in the presence of DPN.

Autophagy and anti-inflammation ameliorate diabetic neuropathy with Rilmenidine

Purpose: To evaluate the neuroprotective effects of Rilmenidine on diabetic peripheral neuropathy (DPN) in a rat model of diabetes induced by streptozotocin (STZ). Methods: STZ (60 mg/kg) was administered to adult Sprague-Dawley rats to induce diabetes. On the 30th day after STZ administration, electromyography (EMG) and motor function tests confirmed the presence of DPN. Group 1: Control (n = 10), Group 2: DM + 0.1 mg/kg Rilmenidine (n = 10), and Group 3: DM + 0.2 mg/kg Rilmenidine (n = 10) were administered via oral lavage for four weeks. EMG, motor function test, biochemical analysis, and histological and immunohistochemical analysis of sciatic nerves were then performed. Results: The administration of Rilmenidine to diabetic rats substantially reduced sciatic nerve inflammation and fibrosis and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves from saline-treated rats revealed increased perineural thickness, HMGB-1, tumor necrosis factor-α, and a decrease in nerve growth factor (NGF), LC-3. In contrast, Rilmendine significantly inhibited inflammation markers and prevented the reduction in NGF expression. In addition, Rilmenidine significantly decreased malondialdehyde and increased diabetic rats' total antioxidative capacity. Conclusions: The findings of this study suggest that Rilmenidine may have therapeutic effects on DNP by modulating antioxidant and autophagic pathways.

Exame do pé diabético: fatores de risco de ulceração em pacientes com diabetes mellitus / Examen del pie diabético: factores de riesgo de ulceración en pacientes con diabetes mellitus / Diabetic foot exam: risk factors of ulceration in patients with diabetes mellitus

Objetivo: descrever a evolução dos fatores de risco para o desenvolvimento de úlceras nos pés de pacientes com DM, em três exames subsequentes num período de 3 anos, num centro de especialidades médicas. Método: estudo descritivo, retrospectivo e longitudinal, com 102 pacientes, entre os anos de 2016 e 2019, que realizaram três exames dos pés sequenciais, fundamentado no padrão estabelecido pelo consenso internacional do pé diabético, sendo eles avaliação neuropática, vascular, dermatológica e uso dos calçados, coletado do Sistema do Pé Diabético. Resultados: 86,27% dos pacientes declararam sintomas neuropáticos, principalmente queimação, dormência e formigamento. A maioria hipertensos (74,71%) e idosos (67,65%), desses 13,73% com infarto prévio e 72,55% eram do sexo feminino. Do primeiro ao terceiro exame, o "risco muito baixo" aumentou 7,84% e "risco baixo" 8,83%, já o "risco elevado" reduziu 17,65%. Conclusão: a realização sistemática do exame clínico dos pés, associado a estratégias educativas efetivas, resultam num controle mais eficaz do risco de ulceração.

Objetivo: Describir la evolución de los factores de riesgo para el desarrollo de úlceras en los pies de pacientes con DM, en tres exámenes subsecuentes en un período de 3 años, en un centro de especialidades médicas. Método: estudio descriptivo, retrospectivo y longitudinal, con 102 pacientes, entre los años 2016 y 2019, que realizaron tres exámenes de los pies secuenciales, fundamentado en el patrón establecido por el consenso internacional del pie diabético, siendo ellos evaluación neuropática, vascular, dermatológica y uso de calzado, recogido del Sistema del Pie Diabético. Resultados: 86,27% de los pacientes declararon síntomas neuropáticos, principalmente ardor, entumecimiento y hormigueo. La mayoría hipertensos (74,71%) y ancianos (67,65%), de esos 13,73% con infarto previo y 72,55% eran mujeres. Del primero al tercer examen, el "riesgo muy bajo" aumentó un 7,84% y "riesgo bajo" un 8,83%, mientras que el "riesgo alto" redujo un 17,65%. Conclusión: la realización sistemática del examen clínico de los pies, asociado a estrategias educativas efectivas, resultan en un control más eficaz del riesgo de ulceración.

Objective: to describe the evolution of risk factors for the development of foot ulcers in patients with DM, in three subsequent exams over a period of 3 years, in a medical specialty center. Method: a descriptive, retrospective and longitudinal study, with 102 patients, between the years 2016 and 2019, who performed three sequential foot exams, based on the standard established by the international consensus of the diabetic foot, being use of footwear, collected from the Diabetic Foot System. Results: 86.27% of patients reported neuropathic symptoms, mainly burning, numbness and tingling. Most were hypertensive (74.71%) and elderly (67.65%), of these, 13.73% had previous infarction and 72.55% were female. From the first to the third examination, the "very low risk" increased 7.84% and the "low risk" 8.83%, while the "high risk" reduced 17.65%. Conclusion: the systematic clinical feet exam, associated with effective educational strategies, results in a more effective control of the risk of ulceration.

Study on the value of Michigan nerve screening scale, pain and tactile temperature detection and vibration perception threshold in diagnosing diabetic peripheral neuropathy / 中国医师进修杂志

Objective:To analyze the diagnostic value of Michigan nerve screening Scale (MNSI), pain, touch and temperature detection combined with vibratory perception threshold (VPT) in diabetic peripheral neuropathy (DPN).Methods:A total of 500 patients with type 2 diabetes mellitus (T2DM) who received inpatient treatment in Xinhua Hospital Chongming Branch Affiliated of Shanghai Jiao Tong University School of Medicine from January to December 2018 were selected. Sixty four patients with DPN were enrolled in the DPN group, and the remaining 436 patients were enrolled in the no-DPN group. The clinical data and the results of MNSI scale, pain, touch and temperature detection thresholds and VPT of the two groups were compared. Receiver operating characteristic (ROC) curve was drawn to analyze the clinical value of single and combined examination indicators in the diagnosis of DPN.Results:MNSI symptom questionnaire score and MNSI physical examination score in DPN group were higher than those in no-DPN group: (3.00 ± 1.35) scores vs. (1.69 ± 0.52) scores, (1.57 ± 0.50) scores vs. (1.01 ± 0.24) scores; the proportion of touch regression, pain regression and temperature regression was significantly higher than that in no-DPN group; and the levels of VPT in the DPN group was higher than that in the no-DPN group: (26.34 ± 5.03) V vs. (17.97 ± 6.82) V, there were statistical differences ( P<0.01). When the single index was diagnosed, the area under the curve (AUC) value of VPT was the highest (0.825), and significantly higher than the pain, touch and temperature detection ( P<0.01). The AUC value of VPT + MNSI in combined diagnosis was the highest (0.738), and the sensitivity and specificity of DPN diagnosis were 51.56% and 96.10%, respectively. Conclusions:Compared with MNSI scale score, sensory detection such as pain, touch and temperature, VPT has the best diagnostic efficiency for DPN, while combined with MNSI, the specificity can be further improved, but the sensitivity decreases, which is worthy of clinical attention.

Evaluation of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy / 中国医师进修杂志

Objective:To investigate the application of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy (DPN) and its effect on motor and sensory nerve conduction and inflammatory factors.Methods:One hundred and fiftypatients with DPN treated in Beihai People′s Hospital from June 2018 to March 2020 were randomly divided into low-dose group and high-dose group, with 75 cases in each group. On the basis of routine treatment, the low-dose group was given alprostadil + mouse nerve growth factor 18 μg/time, once a day. The high-dose group was given alprostadil+mouse nerve growth factor 30 μg/time, once a day, both two groups were treated for 3 weeks. The curative effect, motor and sensory nerve conduction velocity and inflammatory index tumor necrosis factor-α(TNF-α)interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC) and cost-effectiveness analysis, adverse reactions between the two groups were compared.Results:There was no significant difference in the total effective rate between the low dose group and the high dose group ( P>0.05). After 1 and 3 weeks of treatment, the levels ofmotor and sensory nerve conduction velocity and TNF-α, IL-6, hs-CRP and WBC in the two groups has no significant differences ( P>0.05). The cost of each unit effect in the low-dose group was 43.11 Yuan, and the cost of each unit effect in the high-dose group was 57.58 Yuan. The high-dose group was higher than that in the low-dose group, and the high-dose group paid 572.56 Yuan more than the low-dose group for each additional unit effect. There was no significant difference in the total incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Alprostadil combined with 18 μg mouse nerve growth factor in the treatment of DPN has a similar improvement effect on clinical symptoms, motor and sensory nerve conduction and inflammatory factors, and has advantages in cost-effectiveness.

Diabetic peripheral neuropathy / 中华神经科杂志

Diabetes peripheral neuropathy (DPN) is one of the most common complications of diabetes. It not only causes physical disability and unbearable pain, but also may lead to emotional and psychological problems, reduce the quality of life of patients, and increase mortality. Although early diagnosis of diabetes may improve the clinical prognosis, the occurrence of DPN is sometimes unavoidable and the treatment is limited. This article summarizes the clinical features, diagnosis, investigations and treatment of DPN by reviewing the latest literature.

Clinical study of Qigui Tangtongning Granules combined with conventional western medicine in treating diabetic peripheral neuropathy syndrome of Qi deficiency and blood stasis / 国际中医中药杂志

Objective:To observe the clinical efficacy of Qigui Tangtongning Granules in the treatment of diabetic peripheral neuropathy (DPN) with qi deficiency and blood stasis.Methods:Prospective cohort study. A total of 80 DPN patients with Qi deficiency and blood stasis in Endocrinology Department of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2021 to May 2022 who met the inclusion criteria were divided into 2 groups by random number table method, with 40 cases in each group. The control group was treated with epalrestat on the basis of routine hypoglycemia, and the treatment group was treated with Qigui Tangtongning Granules on the basis of control group. Both groups were treated for 8 weeks. TCM syndromes were scored before and after treatment. Disease severity was assessed using the Toronto Clinical Scoring System (TCSS). The motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of median nerve and common peroneal nerve were detected by electromyography/induced potentiometer. Serum CRP, TNF-α and IL-6 were detected by ELISA, fasting blood glucose (FPG) and two hours post-meal blood glucose (2 hPG) were detected by automatic biochemical analyzer, and glycosylated hemoglobin (HbA1c) was detected by automatic HBA1C analyzer. Adverse reactions were recorded and clinical efficacy was evaluated.Results:The total effective rate was 95.0% (38/40) in the treatment group and 77.5% (31/40) in the control group, the difference between the two groups was statistically significant ( χ2=5.17, P=0.023). After treatment, the TCM syndrome score and TCSS score of the treatment group were significantly lower than those in the control group ( t=-3.19 and -7.63, P<0.01); Median nerve SNCV [(47.90±4.51) m/s vs. (44.76±3.72) m/s, t=3.40], MNCV [(53.79±3.65) m/s vs. (51.32±4.25) m/s, t=2.79] and common peroneal nerve SNCV [(44.21±2.08) m/s vs. (40.51±2.49) m/s, t=7.23], MNCV [(44.63±4.72) m/s vs. (41.36±4.87) m/s, t=3.05] were significantly higher than those in the control group ( P<0.01); FPG [(5.05±0.63) mmol/L vs. (7.05±1.23) mmol/L, t=-9.17], 2 hPG [(9.10±1.64) mmol/L vs. (12.19±2.61) mmol/L, t=-6.35], HbA1c [(6.79±0.90) % vs. (7.22±1.02) %, t=-2.02] were significantly lower than those in the control group ( P<0.01 or P<0.05); TNF-α [(15.75±5.44) ng/L vs. (32.01±5.33) ng/L, t=-13.51], hs-CRP [(2.58±0.80) mg/L vs. (3.79±1.04) mg/L, t=-5.83], IL-6 [(18.20±4.92) ng/L vs. (29.97±5.18) ng/L, t=-10.41] were significantly lower than those in the control group ( P<0.01). No obvious adverse reactions were observed in 2 groups during treatment. Conclusion:Qigui Tangtongning Granules combined with conventional Western medicine can improve nerve conduction velocity, reduce inflammation and improve clinical efficacy in DPN patients with Qi-deficiency and blood-stasis syndrome.

Recording cutaneous silent period parameters in hereditary and acquired neuropathies / Registro do período de silêncio cutâneo em neuropatias adquiridas e hereditárias

Abstract Background Cutaneous silent period (CSP) is the interruption in muscle activity after painful stimulation of a sensory nerve. Objective The aim of the present study is to assess CSP changes in patients with polyneuropathy (PNP). Methods The present study was carried out to assess CSP in individuals with diabetes (DM) and Charcot-Marie-Tooth (CMT) disease. The sample comprised 24 individuals with DM, 10 individuals with CMT1 disease, and 10 individuals with CMT2 disease. The control group (CG) consisted of 59 individuals. Results The mean latencies recorded for the upper limbs in the CG were 79.2 milliseconds (onset latency), 69.3 milliseconds (50% reduction latency), 112.2 milliseconds (end latency), and 33.1 milliseconds (CSP duration). On the other hand, the mean latencies recorded for the lower limbs were 99.0 milliseconds (onset latency), 85.0 milliseconds (50% reduction latency), 136.9 milliseconds (end latency), and 38.2 milliseconds (CSP duration). The mean latencies recorded for the CG were significantly lower than the ones recorded for other groups, both in the upper and lower limbs. Conclusions Cutaneous silent period values recorded for the CG in the present study were close to the ones reported in studies available in the literature. Abnormal CSP parameters were observed in the group of individuals with PNP. The end latency in the lower limbs helped differentiating the demyelinating subgroup from the axonal one.

Resumo Antecedentes Período de silêncio cutâneo (PSC) é uma interrupção da atividade muscular após a estimulação dolorosa de um nervo sensitivo. Objetivo O presente estudo tem como objetivo avaliar alterações do PSC em indivíduos com polineuropatia. Métodos O presente estudo avaliou PSC em indivíduos com diabetes mellitus (DM) e com doença de Charcot-Marie-Tooth (CMT). A amostra compreendia 24 indivíduos com DM, 10 indivíduos com CMT tipo 1 e 10 indivíduos com CMT tipo 2. Um grupo controle continha 59 indivíduos. Resultados A média das latências do PSC registradas nos membros superiores no grupo controle foi 79,2 milissegundos (latência de início), 69,3 milissegundos (latência com redução de 50%), 112,2 milissegundos (latência final) e 33,1 milissegundos (duração do PSC). Por outro lado, a média das latências do PSC registradas nos membros inferiores foi 99,0 milissegundos (latência de início), 85,0 milissegundos (latência com redução de 50%), 136,9 milissegundos (latência final) e 38,2 milissegundos (duração do PSC). A média das latências registradas no grupo controle foi significativamente menor do que as registradas nos outros grupos (DM e CMT), tanto nos membros inferiores quanto nos superiores. Conclusões Os valores do PSC registrados no grupo controle no presente estudo estiveram próximos aos reportados na literatura. Parâmetros anormais foram observados no grupo de indivíduos com polineuropatia. A latência final do PSC obtida nos membros inferiores ajudou a diferenciar os subgrupos desmielinizantes e axonais.

Complicaciones crónicas microvasculares en usuarios con diabetes mellitus tipo 2 de una ciudad andina del Perú / Chronic microvascular complications in users with type 2 diabetes mellitus from an Andean city in Peru

RESUMEN Objetivo Determinar las complicaciones crónicas microvasculares en usuarios con diabetes mellitus tipo 2 de una ciudad andina del Perú. Métodos Estudio descriptivo, transversal. Se evaluaron las complicaciones crónicas microvasculares en 22 usuarios con diabetes mellitus tipo 2: la neuropatía, mediante la escala Michigan Diabetic Neuropathy Score; la retinopatía, a través de la biomicroscopía dilatada y cámara retinal, según las pautas de las guías clínicas del Consejo Internacional de Oftalmología, y la nefropatía, según la tasa de filtración glomerular basada en la guía técnica del Ministerio de Salud. Se obtuvieron frecuencias absolutas y relativas y el chi cuadrado de bondad de ajuste con el 95% de confianza y un p-valor significativo <0,05. Resultados La frecuencia de neuropatía fue de 36,4%; el 75% de adultos mayores y el 57,2% de pacientes con 10 o más años con diabetes presentaron neuropatía leve o moderada. La frecuencia de retinopatía fue de 27,3%; el 57,2% de pacientes con 10 o más años con diabetes presentaron algún grado de retinopatía. La frecuencia de nefropatía fue de 4,5%; el 59,1% estuvieron en riesgo de nefropatía y el 50,0% de adultos mayores presentaron posible nefropatía diabética. Conclusión Las complicaciones crónicas más frecuentes en los usuarios evaluados fueron la neuropatía y retinopatía en algún grado de desarrollo. La diferencia con los valores contrastados de otros contextos fue estadísticamente significativa. La actuación oportuna y eficiente ralentizaría la aparición de estas complicaciones, dotando a los afectados de una calidad de vida más placentera.

ABSTRACT Objective To determine the chronic microvascular complications in users with type 2 diabetes mellitus in an Andean city in Peru. Methods Descriptive, cross-sectional study. Chronic microvascular complications were evaluated in 22 users with type 2 diabetes mellitus: neuropathy was tested using the Michigan Diabetic Neuropathy Score; retinopathy, using dilated biomicroscopy and retinal camera, according to the guidelines of the International Council of Ophthalmology clinical guidelines, and nephropathy, according to the glomerular filtration rate based on the technical guide of the Ministry of Health. Absolute and relative frequencies and chi-square goodness of fit were obtained with 95% confidence and a significant p-value <0.05. Results The frequency of neuropathy was 36.4%, of which 75% of older adults and 57.2% of patients with diabetes for 10 years or more had mild or moderate neuropathy. The frequency of retinopathy was 27.3%, of which 57.2% of patients with diabetes for 10 years or more had some degree of retinopathy. The frequency of nephropathy was 4.5%, of which 59.1% were at risk of nephropathy, and 50.0% of older adults had possible diabetic nephropathy. Conclusion The most frequent chronic complications in the evaluated users were neuropathy and retinopathy in some degree of development. The difference with the contrasting values of other contexts was statistically significant. Timely and efficient action would slow down the appearance of these complications, giving those affected a more pleasant quality of life.

Fatores associados ao maior risco de ulceração nos pés de indivíduos com diabetes mellitus / Factors associated with the greatest risk of ulceration on the feet of individuals with diabetes mellitus

Objetivo: Diante da alta prevalência do Diabetes Mellitus, o estudo se propõe a identificar os fatores associados ao maior risco de desenvolver úlceras nos membros inferiores. Métodos: O trabalho foi exploratório-descritivo, transversal e com abordagem quantitativa. A amostra foi composta por pacientes com Diabetes acima de 18 anos de um serviço de saúde particular e um público. A coleta de dados ocorreu através de anamnese, exame físico e procura em prontuário. A análise estatística foi realizada pelo Programa SPSS 20.0. Resultados: Obteve-se 102 participantes no estudo, destes, 67,6% apresentaram critérios diagnósticos para Polineuropatia Simétrica Distal. Os fatores associados ao risco de ulceração foram: o envelhecimento, a maior duração da Diabetes, hipertensão, doença arterial periférica e a presença de sintomas típicos da Polineuropatia. Conclusão: É necessário investir na prevenção de úlceras em indivíduos com Diabetes através de educação em saúde e acompanhamento por profissionais da saúde (AU)

Objective: Given the high prevalence of Diabetes Mellitus, the study aims to identify the factors associated with a higher risk of developing ulcers in the lower limbs. Methods: The work was exploratory-descriptive, transversal and with a quantitative approach. The sample consisted of patients with Diabetes over 18 years of age from a private and a public health service. Data collection occurred through anamnesis, physical examination and search in medical records. Statistical analysis was perform using the SPSS 20.0 program. Results: 102 study participants were obtained, of wich 67,6% had diagnostic criteria for Distal Symmetric Polyneuropathy. Factors associated with the risk of ulceration were: aging, longer duration of diabetes, hypertension, peripheral arterial disease and the presence of typical symptoms of polyneuropathy. Conclusion: It is necessary to invest in the prevention of ulcers in individuals with Diabetes, through health education and monitoring by health professionals.Keywords: Diabetes Mellitus, Diabetic neuropathies, Polyneuropathies, Foot ulcer, Diabetic foot (AU)

Fatores associados ao maior risco de ulceração nos pés de indivíduos com diabetes mellitus / Factors associated with the greatest risk of ulceration on the feet of individuals with diabetes mellitus

RESUMO: Objetivo: Diante da alta prevalência do Diabetes Mellitus, o estudo se propõe a identificar os fatores associados ao maior risco de desenvolver úlceras nos membros inferiores. Métodos: O trabalho foi exploratório-descritivo, transversal e com abordagem quantitativa. A amostra foi composta por pacientes com Diabetes acima de 18 anos de um serviço de saúde particular e um público. A coleta de dados ocorreu através de anamnese, exame físico e procura em prontuário. A análise estatística foi realizada pelo Programa SPSS 20.0. Resultados: Obteve-se 102 participantes no estudo, destes, 67,6% apresentaram critérios diagnósticos para Polineuropatia Simétrica Distal. Os fatores associados ao risco de ulceração foram: o envelhecimento, a maior duração da Diabetes, hipertensão, doença arterial periférica e a presença de sintomas típicos da Polineuropatia. Conclusão: É necessário investir na prevenção de úlceras em indivíduos com Diabetes através de educação em saúde e acompanhamento por profissionais da saúde. (AU)

ABSTRACT: Objective: Given the high prevalence of Diabetes Mellitus, the study aims to identify the factors associated with a higher risk of developing ulcers in the lower limbs. Methods: The work was exploratory-descriptive, transversal and with a quantitative approach. The sample consisted of patients with Diabetes over 18 years of age from a private and a public health service. Data collection occurred through anamnesis, physical examination and search in medical records. Statistical analysis was perform using the SPSS 20.0 program. Results: 102 study participants were obtained, of wich 67,6% had diagnostic criteria for Distal Symmetric Polyneuropathy. Factors associated with the risk of ulceration were: aging, longer duration of diabetes, hypertension, peripheral arterial disease and the presence of typical symptoms of polyneuropathy. Conclusion: It is necessary to invest in the prevention of ulcers in individuals with Diabetes, through health education and monitoring by health professionals. (AU)

The voxel-based morphometry of cerebral gray matter volume in patients with diabetic peripheral neuropathy / 中国医师杂志

Objective:To explore the structural alterations in functional brain areas of patients with diabetic peripheral neuropathy (DPN) using voxel-based morphometry (VBM), and to investigate the abnormal region of grey matter and its distribution in DPN.Methods:A total of 124 patients with DPN and 88 patients with type 2 diabetes without DPN (NDPN) diagnosed in Haikou Hospital and the First Affiliated Hospital of Guangdong Pharmaceutical University from June 2019 to December 2020 were selected as the study subjects, and 40 healthy volunteers matched with gender and age were included as the control group.All subjects underwent whole-brain MRI examination, and 3D-T1WI data were collected for post-processing and analysis based on voxel morphological analysis.Results:Compared with NDPN patients, decreased gray matter volume in DPN patients was observed in the bilateral anterior central gyrus and thalamus, with statistical signifcant difference ( P<0.05), and there was no significant difference between the two sides ( P>0.05). Compared with healthy control group, decreased gray matter volume in DPN was observed in the the bilateral anterior central gyrus, central posterior gyrus, superior frontal gyrus and thalamus, with statistical signifcant difference ( P<0.05) and there was no significant difference between the two sides ( P>0.05). Conclusions:DPN patients also have decreased volumes of the brain greymatter, suggesting that the occorrence of DPN patients may be caused by the of injury of central structure.

Serum levels of complement B and D in patients with diabetic peripheral neuropathy and their correlation / 中国医师杂志

Objective:To investigate the serum level and significance of complement factor B (CFB) and complement factor D (CFD) in patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN).Methods:From October 2019 to October 2020, 110 patients with T2DM in the endocrinology department of Affiliated Hospital of Jining Medical College were divided into DPN group ( n=60) and simple T2DM group ( n=50) according to whether or not DPN was combined. In addition, 52 cases of physical examination population in the physical examination center in the same period were selected as the normal control group ( n=52). The serum levels of CFB, CFD and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA). The correlation between CFB, CFD and clinical indexes was analyzed, and the influencing factors of DPN were analyzed by logistic regression. Results:The serum levels of CFB and CFD in DPN group were higher than those in T2DM group and normal control group [CFB: (845.43±101.10)μg/ml vs (792.19±116.59)μg/ml, (739.20±123.43)μg/ml, P<0.05], [CFD: (491.71±41.03)mg/L vs (467.58±45.16)mg/L, (445.16±50.47)mg/L, P<0. 05]. Pearson correlation analysis showed that the serum level of CFB was positively correlated with glycosylated hemoglobin (HbA 1c), fasting plasma glucose (FPG) and TNF-α (all P<0.05) and negatively correlated with triiodothyronine (FT3) and total bilirubin (TBIL) (all P<0.05). Serum CFD level was positively correlated with systolic blood pressure, HbA 1c, FPG and TNF-α (all P<0.05), but negatively correlated with FT3 and TBIL (all P<0.05). Logistic regression analysis showed that CFB and CFD were still influential factors for the occurrence and development of DPN after excluding confounding factors such as systolic blood pressure, HbA 1c, FPG, FT3, DBIL, TBIL and TNF-α. Conclusions:(1) Serum CFB and CFD levels were significantly increased in DPN patients, suggesting that CFB and CFD may be involved in the occurrence and development of DPN. (2) Serum TNF-α level was significantly increased in DPN patients, confirming the role of TNF-α in the pathogenesis of DPN.

Effects of Tangtong formula on the expression of PI3K, Akt and mTOR in sciatic nerve of diabetic peripheral neuropathy rats / 国际中医中药杂志

Objective:To observe the effect of Tangtong formula on the expression of autophagy pathway proteins PI3K, Akt and mTOR in sciatic nerve of DPN rats, and to explore its mechanism. Methods:There were 60 male SD rats, 15 of which were randomly selected as the normal group, and the other rats were used to establish DPN model with STZ + ischemia-reperfusion method. Then they were divided into model group, Tangtong formula low-dose group and Tangtong formula high-dose group, with 15 rats in each group with random number table method. 36.67 g/kg Tangtong formula was administered by gavage in the high-dose group and 18.33 g/kg Tangtong formula was administered by gavage in the low-dose group, once a day. After 8 weeks of continuous gavage, the conduction velocity of sciatic nerve was detected. The mRNA and protein expression levels of PI3K, Akt and mTOR were detected by PCR and Western blot. The structure of sciatic nerve fibers was observed by HE staining. Results:Compared with the model group, the motor nerve conduction velocity, sensory nerve conduction velocity, muscle compound action potential and sensory nerve action potential in the low-dose Tangtong formula group and high-dose Tangtong formula group were increased ( P<0.05). The expression of PI3K mRNA(6.05±0.18, 3.36±0.29 vs. 11.57±1.93), Akt mRNA(1.26±0.13, 0.64±0.04 vs. 1.86±0.06), mTOR mRNA(1.82±0.11, 0.92±0.06 vs. 2.68±0.18) of sciatic nerve in rats of the low-dose and high-dose group were increased ( P<0.05). The expression of PI3K(0.40±0.00, 0.19±0.02 vs. 0.61±0.03), Akt(0.64±0.02, 0.45±0.01 vs. 0.83±0.02), mTOR(0.17±0.01, 0.09±0.00 vs. 0.34±0.01)of sciatic nerve in rats of the low-dose and high-dose group were increased ( P<0.05). The model group's nerve fibers were loose and swollen, myelin sheath became thin, and the axis Atresia, the neuromorphology of the low-dose and high-dose group tended to be normal, and the morphology of myelin sheath and axon were better. Conclusions:Tangtong formula could improve the conduction velocity and potential amplitude of sciatic nerve in DPN rats, reduce nerve injury and demyelinating changes, improve axon morphology and protect nerve fiber structure. Its mechanism might be related to activating PI3K/Akt/mTOR signal pathway and inhibiting excessive autophagy.

The constitution rule of TCM syndromes of diabetic peripheral neuropathy with real world data mining / 国际中医中药杂志

Objective:To annalyze the constitution rule and pathogenesis of Diabetic Peripheral Neuropathy (DPN) by data mining technology, so as to provide a theoretical reference for improving the therapeutic effect of TCM on treating DPN.Methods:343 cases of DPN patients dianosed with four TCM diagostic methods chosen from the Department of Endocrinology of Affiliated Hospital of Traditional Chinese Medicine of Guangzhou Medical University from January 2016 to January 2020 were collected. Statistical analysis software was used to conduct frequency analysis, correlation analysis and cluster analysis, and explained with TCM theory.Results:Among the 343 cases, 143 cases were male and 200 cases were female; Symptoms such as limb numbness, thirst, dry mouth, frequent urination at night, limb pain and so on occur more frequently; The main tongue images include thin white tongue, dark and red tongue or light red tongue; the main pulse conditions include string, fine and deep pulse. Numbness, thirst, dry mouth, thin and white fur, frequent nocturia and so on were closely related with other diseases. Four types of syndrome can be recombined by cluster analysis, which are blood stasis obstructing collaterals syndrome; kidney deficiency and blood stasis syndrome; stomach heat injuring Yin syndrome; spleen deficiency and phlegm dampness syndrome; heat toxin accumulation and syndrome of lingering pathogen due to deficient vital qi.Conclusion:The root of the disease is Yin deficiency with dry heat as the sympotom. Blood stasis runs through the whole process of the disease. The function of spleen and stomach should not be ignored in treatment.

Role of spinal cord mitochondrial autophagy in alleviation of diabetic neuropathic pain by curcumin in mice / 中华麻醉学杂志

Objective:To evaluate the role of spinal cord mitochondrial autophagy in alleviation of diabetic neuropathic pain (DNP) by curcumin in mice.Methods:SPF healthy male C57BL/6 mice, aged 2 months, weighing 20-25 g, in which DNP model was established by intraperitoneal injection of streptozotocin (STZ) 130 mg/kg, were used in this study.A total of 36 mice with successfully established DNP model were divided into 3 groups ( n=12 each) using the random number table method: DNP group, DNP + curcumin group (DPR group), and DNP + curcumin + cyclosporine A group (DRC group). Another 12 C57BL/6 mice were selected and served as normal control group (NC group), and the equal volume of normal saline was intraperitoneally injected.In group DPR, curcumin 200 mg/kg was administered by intragastric gavage, once a day, for 7 consecutive days.In group DRC, the mitochondrial autophagy inhibitor cyclosporine A 10 mg/kg was intrathecally injected once a day for 7 consecutive days before each administration of curcumin.The equal volume of normal saline was administered by intragastric gavage at the same time point, once a day, for 7 consecutive days in group NC and group DNP.The mechanical paw withdrawal threshold (MWT) was measured before intragastric gavage and at 1, 3, 5 and 7 days after intragastric gavage.After the last behavioral testing, the L 4-6 spinal cord tissues were removed for determination of the mitochondrial membrane potential and ROS content (by JC-1 and DCFH-DA combined with flow cytometry), expression of microtubule-associated protein light chain 3 (LC3), Beclin1 and P62 (by Western blot), and mitochondrial autophagosomes (by transmission electron microscopy) and for microscopic examination of the co-expression of LC3-Ⅱwith mitochondrial translocase outer membrane protein 20 (TOM20) (using immunofluorescence double-labeling technique). Results:Compared with group NC, the MWT and mitochondrial membrane potential were significantly decreased, the ROS content and LC3-Ⅱ/Ⅰ ratio were increased, the expression of Beclin1 was up-regulated, the expression of P62 was down-regulated ( P<0.05), the number of mitophagosomes developed was increased, and the co-expression of LC3-Ⅱwith TOM20 was increased in group DNP.Compared with group DNP, the MWT and mitochondrial membrane potential were significantly increased, the ROS content was decreased, and LC3-Ⅱ/Ⅰ ratio was increased, the expression of Beclin1 was up-regulated, the expression of P62 was down-regulated ( P<0.05), the number of mitophagosomes developed was increased, and the co-expression of LC3-Ⅱwith TOM20 was increased in group DPR.Compared with group DPR, the MWT and mitochondrial membrane potential were significantly decreased, the ROS content was increased, LC3-Ⅱ/Ⅰ ratio was decreased, the expression of Beclin1 was down-regulated, the expression of P62 was up-regulated ( P<0.05), the number of mitophagosomes developed was decreased, and the co-expression of LC3-Ⅱ with TOM20 was decreased in group DRC. Conclusions:The mechanism by which curcumin reduces DNP may be related to the up-regulation of mitochondrial autophagy in the spinal cord and improvement in mitochondrial function in mice.

Investigation of nerve fibers in the skin by biopsy: technical aspects, indications, and contribution to diagnosis of small-fiber neuropathy

ABSTRACT Skin biopsy with investigation of small-diameter nerve fibers in human epidermis and dermis has been proven to be a useful method for confirming small-fiber neuropathy. In medical practice, small-fiber neuropathy is increasingly recognized as a leading cause of neuropathic pain. It is a prevalent complaint in medical offices, brought by patients often as a "painful burning sensation". The prevalence of neuropathic pain is high in small-fiber neuropathies of different etiologies, especially in the elderly; 7% of population in this age group present peripheral neuropathy. Pain and paresthesia are symptoms which might cause disability and impair quality of life of patients. The early detection of small-fiber neuropathy can contribute to reducing unhealthy lifestyles, associated to higher incidence of the disease.