Papel de la neuropatía diabética en la aparición y desarrollo del síndrome del pie diabético / Role of Diabetic Neuropathy in the Onset and Development of Diabetic Foot Syndrome

Introducción: La neuropatía diabética es la complicación más frecuente de la diabetes mellitus y una de sus posibles consecuencias es el síndrome del pie diabético. Los médicos del primer nivel de atención deben conocer el comportamiento clínico de la neuropatía diabética y, sobre todo, como influye en la aparición y desarrollo del síndrome del pie diabético. Objetivo: Describir el papel de la neuropatía diabética en la aparición y desarrollo del síndrome del pie diabético. Métodos: Para la obtención de la información se utilizaron como motores de búsqueda de información científica los correspondientes a Scielo, Pubmed, y Google Académico. Se usaron como palabras clave: diabetes mellitus; neuropatía diabética; pie diabético; síndrome de pie diabético; úlcera de pie diabético; ataque de pie diabético. Se evaluaron diferentes trabajos de revisión, investigación y páginas web, y se excluyeron los artículos que tuvieran más de 10 años de publicados, en idiomas diferentes al español, portugués e inglés y que no se refirieran al tema de estudio a través del título. Esto permitió la cita de 45 referencias bibliográficas. Conclusiones: La neuropatía diabética constituye el principal factor de riesgo en la aparición y desarrollo del síndrome del pie diabético, sobre todo cuando se asocia a artropatía (defectos podálicos), enfermedad vascular periférica y/o sepsis. El control de la glucemia, la detección temprana del pie de riesgo y el cuidado preventivo de los miembros inferiores, repercutirá favorablemente en la salud y bienestar del paciente(AU)

Introduction: Diabetic neuropathy is the most frequent complication of diabetes mellitus and one of its possible consequences is diabetic foot syndrome. First level of care physicians should know the clinical behavior of diabetic neuropathy and, above all, how it influences the appearance and development of diabetic foot syndrome. Objective: To describe the role of diabetic neuropathy in the appearance and development of diabetic foot syndrome. Methods: To obtain the information, SciELO, PubMed and Google Scholar were used as search engines for scientific information. The keywords used were: diabetes mellitus; diabetic neuropathy; diabetic foot; diabetic foot syndrome; diabetic foot ulcer; diabetic foot attack. Different review papers, research papers and web pages were evaluated and articles that were more than 10 years old and published in languages other than Spanish, Portuguese and English and that did not refer to the subject of the study through the title were excluded. This allowed the citation of 45 bibliographic references. Conclusions: Diabetic neuropathy constitutes the main risk factor in the appearance and development of diabetic foot syndrome, especially when associated with arthropathy (foot defects), peripheral vascular disease and/or sepsis. Glycemic control, early detection of the foot at risk and preventive care of the lower limbs will have a favorable impact on the patient's health and well-being(AU)

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.

Avaliação de risco dos pés de pessoas com diabetes mellitus residentes de um bairro de Pelotas, Rio Grande do Sul, Brasil / Prevalence and risk classification of feet with diabetic neuropathy mellitus in residents of a neighborhood of Pelotas, Rio Grande do Sul, Brazil / Prevalencia y clasificación de riesgo de pies con neuropatía diabética mellitus en residentes de un barrio de Pelotas, Rio Grande do Sul, Brasil

Introdução: O Diabetes Mellitus pode ocasionar inúmeras complicações crônicas ao longo do tempo. Dentre elas, destaca-se a neuropatia diabética que compreende um conjunto de doenças que atinge as fibras nervosas. Este estudo tem como objetivo descrever o grau de risco dos pés de pessoas com Diabetes Mellitus que utilizam insulina, residentes em um bairro da zona urbana de Pelotas, RS. Materiais e métodos: Trata-se de um estudo quantitativo descritivo. A coleta de dados ocorreu na zona norte da cidade de Pelotas, Rio Grande do Sul. A coleta de dados foi realizada na residência dos participantes, entre maio e junho de 2017, contou com a participação de 39 pessoas com pés com neuropatia por Diabetes Mellitus. Resultados: Os entrevistados tinham, predominantemente diabetes tipo 2, perfazendo 89,7%, sendo o tempo de diagnóstico, com o mínimo de 3 anos, até 40 anos de evolução da doença. Sobre a avaliação da neuropatia diabética, 43,6% apresentam dor ao caminhar. Dormência e perda de sensibilidade foi mencionado por 41%. Conclusão: Foi possível elencar o grau de risco para complicações nos pés de usuários com Diabetes Mellitus, esse achado demonstra a importância que as equipes de saúde têm na prevenção de doenças, assim como na promoção da saúde, evitando as ulcerações e posteriores, amputações.

Introduction: Diabetes Mellitus can cause numerous chronic complications over time. Among them, diabetic neuropathy stands out, which comprises a set of diseases that affect the nerve fibers. This study aims to describe the degree of risk of the feet of people with Diabetes Mellitus who use insulin, living in a neighborhood in the urban area of Pelotas, RS. Materials and methods: This is a descriptive quantitative study. Data collection took place in the northern part of the city of Pelotas, Rio Grande do Sul. Data collection was carried out at the participants' homes, between May and June 2017, with the participation of 39 people with feet with Diabetes Mellitus neuropathy. Results: Respondents had predominantly type 2 diabetes, accounting for 89.7%, with the time since diagnosis, with a minimum of 3 years, up to 40 years of disease evolution. Regarding the assessment of diabetic neuropathy, 43.6% present pain when walking. Numbness and loss of sensation was mentioned by 41%. Conclusions: It was possible to list the degree of risk for complications in the feet of users with Diabetes Mellitus, this finding demonstrates the importance that health teams have in preventing diseases, as well as in promoting health, avoiding ulcerations and subsequent amputations.

Introducción: La Diabetes Mellitus puede causar numerosas complicaciones crónicas con el tiempo. Entre ellas destaca la neuropatía diabética, que comprende un conjunto de enfermedades que afectan a las fibras nerviosas. Este estudio tiene como objetivo describir el grado de riesgo de los pies de personas con Diabetes Mellitus usuarias de insulina, residentes en un barrio del área urbana de Pelotas, RS. Materiales y Métodos: Se trata de un estudio cuantitativo descriptivo. La recolección de datos ocurrió en la zona norte de la ciudad de Pelotas, Rio Grande do Sul. La recolección de datos se realizó en los domicilios de los participantes, entre mayo y junio de 2017, con la participación de 39 personas con pies con neuropatía Diabética Mellitus. Resultados: Los encuestados tenían predominantemente diabetes tipo 2, representando el 89,7%, con el tiempo desde el diagnóstico, con un mínimo de 3 años, hasta los 40 años de evolución de la enfermedad. En cuanto a la valoración de la neuropatía diabética, el 43,6% presenta dolor al caminar. El 41% mencionó entumecimiento y pérdida de sensibilidad. Conclusiones: Se pudo enumerar el grado de riesgo de complicaciones en los pies de los usuarios con Diabetes Mellitus, este hallazgo demuestra la importancia que tienen los equipos de salud en la prevención de enfermedades, así como en la promoción de la salud, evitando ulceraciones y posteriores amputaciones.

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.

Systematic review and Meta-analysis of efficacy and safety of Tangmaikang Granules in treatment of diabetic peripheral neuropathy / 中国中药杂志

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.

Role of NLRP3 inflammasome in diabetic neuropathy and prevention and treatment with traditional Chinese medicine / 中国中药杂志

As one of the most frequent complications of diabetes, diabetic neuropathy often involves peripheral and central nervous systems. Neuroinflammation is the key pathogenic factor of secondary nerve injury in diabetes. NOD-like receptor pyrin domain-containing 3(NLRP3) inflammasome is a group of subcellular multiprotein complexes, including NLRP3, apoptosis associated speck-like protein(ASC), and pro-cysteinyl aspartate specific proteinase 1(pro-caspase-1). NLRP3 inflammasome is an inducer of innate immune responses. Its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, triggers cell death and uncontrolled autophagy, activates glial cells, facilitates peripheral immune cell infiltration, and initiates amyoid β(Aβ)-tau cascade reactions. As a result, it contributes to the central nerve, somatic nerve, autonomic nerve, and retinal nerve cell damage secondary to diabetes. Therefore, due to its key role in the neuroinflammation responses of the body, NLRP3 inflammasome may provide new targets for the treatment of diabetic neuropathy. With multi-target and low-toxicity advantages, traditional Chinese medicine plays a vital role in the treatment of diabetic neuropathy. Accumulating evidence has shown that traditional Chinese medicine exerts curative effects on diabetic neuropathy possibly through regulating NLRP3 inflammasome. Although the role of NLRP3 inflammasome in diabetes and related complications has been investigated in the literature, systematical studies on drugs and mechanism analysis for secondary neuropathy are still lacking. In this article, the role of NLRP3 inflammasome in diabetic neuropathy was explored, and the research progress on traditional Chinese medicine in the treatment of diabetic neuropathy through NLRP3 inflammasome was reviewed.

Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory Axons / 神经科学通报·英文版

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.

A nonobstructive condition: Medial arterial calcification / 中南大学学报(医学版)

Vascular calcification, including intimal and medial calcification, is closely associated with a significant increase in cardiovascular diseases. Although increased understandings were achieved, people still know much more about intimal calcification than medial calcification because the latter doesn't obstruct the arterial lumen, commonly considered as a non-significant finding. We clarified the pathologic characteristic of medial calcification, its difference from intimal calcification, principally focused on its clinical relevance, such as diagnosis, nosogenesis, and hemodynamics. We underline the importance of identifying and distinguishing medial calcification, understanding its effect to local/systematic arterial compliance, and relationship to diabetic neuropathy. Recent studies emphasize do not ignore its predictive role in cardiovascular mortality. It is of great clinical significance to summarize the mechanisms of occurrence, lesion characteristics, diagnostic methods, pathogenic mechanisms, hemodynamic changes, and the distinction as well as association of intimal calcification with intimal calcification.

Lianmei Qiwu Decoction relieves diabetic cardiac autonomic neuropathy by regulating AMPK/TrkA/TRPM7 signaling pathway / 中国中药杂志

This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.

Polineuropatia diabética assintomática induzida pelo uso crônico de metformina e correlação com vitamina B12 / Asymptomatic diabetic polyneuropathy induced by chronic metformin use and correlation with vitamin B12

Introdução: Diabetes Mellitus é doença metabólica, caracterizada pela deficiência absoluta ou relativa de insulina, que acomete cerca de 382 milhões de pessoas em todo mundo, tendo uma das complicações mais comuns a polineuropatia. A Metformina, medicamento amplamente utilizado como tratamento do Diabetes, foi descrita como responsável, em algumas literaturas, por causar ou agravar deficiência de vitamina B12, que está similarmente relacionada ao desenvolvimento de polineuropatia.Métodos: Nesse sentido, foi conduzido um estudo no município de Soledade ­ RS, com objetivo de verificar se essa relação é condizente com a realidade da localidade. Foram escolhidos 58 pacientes, dos quais 30 responderam questionários adaptados baseados na literatura e na Classificação de Neuropatia de Michigan (MNSS-Brasil), então colhidos 5 ml de sangue venoso da fossa antecubital, preparado soro do qual uma alíquota foi separada para determinação bioquímica da vitamina B12.Resultados: Analisando os resultados, a maioria dos pacientes analisados apresentou sintomas de polineuropatia, e 10% deste, deficiência vitamínica.Conclusão: nenhuma variável explicou a correlação do uso crônico da Metformina, dose e gênero com a deficiência da vitamina B12, o que indica que não há evidências fortes o suficiente que sustentem esse fato, de acordo com as particularidades da localidade analisada.

Introduction: Diabetes Mellitus is a metabolic disease, characterized by absolute or relative insulin deficiency, which affects about 382 million people, with polyneuropathy being one of the most common complications. Metformin, a drug widely used as a treatment for diabetes, has been described as responsible, in some literature, for causing or aggravating vitamin B12 deficiency, which is similarly related to the development of polyneuropathy.Methods: In this sense, a study was conducted in Soledade ­ RS, in order to verify whether this relationship is consistent with the reality of the locality. Fifty-eight patients were selected, of which 30 answered adapted questionnaires based on the literature and on the Michigan Neuropathy Classification (MNSS-Brazil), then 5 ml of venous blood was collected from the antecubital fossa, serum prepared from which an aliquot was separated for biochemical determination of the vitamin B12.Results: Analyzing the results, most of these patients presented symptoms of polyneuropathy and, 10% of them, vitamin deficiency.Conclusion: no variable explained the correlation of chronic use of Metformin, dose and gender with vitamin B12 deficiency, which indicates that there is not enough evidence to support this fact, according to the particularities of the analyzed locality.

Algunos aspectos actualizados sobre la polineuropatía diabética / Some up-to-date aspects on the diabetic polyneuropathy

La diabetes mellitus es una enfermedad crónica que puede causar complicaciones multiorgánicas como la polineuropatía diabética, con el consecuente trastorno invalidante a quienes la padecen. Por tal motivo, se realizó una revisión bibliográfica exhaustiva con el objetivo de actualizar algunos aspectos importantes sobre esta afección, tales como concepto, factores de riesgo, mecanismos patogénicos, clasificación, diagnóstico y tratamiento, entre otros. Se concluye que esta enfermedad se asocia con varios factores de riesgo, su diagnóstico es fundamentalmente clínico y como tratamiento se considera el control glucémico, el cuidado de los pies y el uso de fármacos.

The diabetes mellitus is a chronic disease that can cause multiorganic complications as the diabetic polyneuropathy, with the consequent invalidant disorder to whom suffer from it. For such a reason, an exhaustive literature review was carried out with the objective of upgrading some important aspects on this affection, such as concept, risk factors, pathogenic mechanisms, classification, diagnosis and treatment, among others. It was concluded that this disease is associated with several risk factors, its diagnosis is fundamentally clinical and the glycemic control, the care of feet and the use of medicines are considered as treatment.

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)

An experimental study of tangzhouling on morphological changes of nissl bodies in the dorsal root ganglion of DM rats / Un estudio experimental de tangzhouling sobre los cambios morfológicos de los cuerpos de nissl en el ganglio de la raíz dorsal de ratas DM

SUMMARY: This study aims to investigate the effect of Tangzhouling on the morphological changes of Nissl bodies in the dorsal root ganglion of DM Rats. In this study, 69 rats were randomly divided into a control group (n = 10) and a model group (n = 59). The rats in the model group were randomly divided into a diabetic group (n = 11), a vitamin C group (n = 12), a low dose Tangzhouling group (n = 12), a medium dose Tangzhouling group (n = 12) and a high dose Tangzhouling group (n = 12). The dose of Tangzhouling in the low dose group was 5 times that of the adult dose, being 0.44g/kg/d. The dose of Tangzhouling in the medium dose group was 10 times that of the adult dose, being 0.88g/kg/d. The dose of Tangzhouling in the high dose group was 20 times that of the adult dose, being 1.75g/kg/d. All doses above are crude drug dosages. Rats in the vitamin C group were given 10 times the dose of an adult, being, 0.05 g/ kg/d. The diabetic group and the control group were given the same amount of distilled water. Drug delivery time is 16 weeks. The dorsal root ganglion was placed in a freezing tube at the end of the experiment. The morphological changes of Nissl bodies in the dorsal root ganglion were detected by HE and Nissl staining. The study results showed that vitamin C had no significant effect on the quantity, size and nucleolus. Tangzhouling can improvee the morphology, quantity and nucleolus of Nissl bodies to a certain extent, and the high dose is better than the lower dose. Tangzhouling capsules can improve the nerve function of DM rats through Nissl bodies.

RESUMEN: Este estudio tuvo como objetivo investigar el efecto de Tangzhouling en los cambios morfológicos de los cuerpos de Nissl en el ganglio de la raíz dorsal de las ratas DM. En este estudio, 69 ratas se dividieron aleatoriamente en un grupo control (n = 10) y un grupo modelo (n = 59). Las ratas del grupo modelo se dividieron aleatoriamente en un grupo diabéticos (n = 11), un grupo vitamina C (n = 12), un grupo de dosis baja de Tangzhouling (n = 12), un grupo de dosis media de Tangzhouling (n = 12) y un grupo de dosis alta de Tangzhouling (n = 12). La dosis de Tangzhouling en el grupo de dosis baja fue 5 veces mayor que la dosis del adulto, siendo 0,44 g/kg/d. La dosis de Tangzhouling en el grupo de dosis media fue 10 veces mayor que la dosis del adulto, siendo 0,88 g/kg/d. La dosis de Tangzhouling en el grupo de dosis alta fue 20 veces mayor que la dosis del adulto, siendo 1,75 g/kg/d. Todas las dosis anteriores son dosis de fármaco crudo. Se les administró 10 veces la dosis de un adulto a las ratas del grupo vitamina C, siendo 0,05 g/kg/d. El grupo de diabéticos y el grupo de control recibieron la misma cantidad de agua destilada. El tiempo de entrega del fármaco fue de 16 semanas. El ganglio de la raíz dorsal se colocó en un tubo de congelación al final del experimento. Los cambios morfológicos de los cuerpos de Nissl en el ganglio de la raíz dorsal se detectaron mediante tinción de HE y Nissl. Los resultados del estudio mostraron que la vitamina C no tuvo un efecto significativo sobre la cantidad, el tamaño y el nucléolo. Tangzhouling puede mejorar la morfología, la cantidad y el nucléolo de los cuerpos de Nissl hasta cierto punto, y es mejor la dosis alta que la dosis baja. Las cápsulas de Tangzhouling pueden mejorar la función nerviosa de las ratas DM a través de los cuerpos de Nissl.

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)

Tetrahydropalmatine alleviated diabetic neuropathic pain by inhibiting activation of microglia via p38 MAPK signaling pathway / 中国中药杂志

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.

Metabolomics in Diabetic Neuropathy / 中国医学科学院学报

Diabetic neuropathy is a common diabetic complication.The application of metabolomics in the research on diabetic neuropathy is beneficial for us to understand the pathophysiological processes and overall metabolic disturbance of the nervous system under the condition of hyperglycemia,decipher the pathogenesis of diabetic neuropathy,and mine the potential biomarkers for clinical diagnosis and treatment.Long-term hyperglycemia may lead to disorders in multiple pathways,such as tricarboxylic acid circle,amino acid metabolism,and lipid metabolism.These metabolic changes are closely associated with the injuries of the peripheral and central nervous system.In the paper,we reviewed the metabolomics-based studies about diabetic neuropathy in the last five years.