Effect of empagliflozin in peripheral diabetic neuropathy of patients with type 2 diabetes mellitus.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most dominant cause of neuropathy worldwide, and there has been no specific treatment until now. The aim of the current study was to assess the probable protective effect of empagliflozin in type 2 diabetics who are suffering from DPN. METHODS: Fifty eligible type 2 diabetes mellitus (T2DM) cases with diabetic peripheral neuropathy were recruited in this study and classified into 2 groups. Group I (n=25) (control group) received placebo tablets once daily. Group II (n=25) (empagliflozin group) received empagliflozin 25mg once daily for three months. Empagliflozin efficacy was evaluated using electrophysiological studies, and HbA1c levels, the brief pain inventory short-form item (BPI-SF) score, the diabetic neuropathy symptom (DNS) score, the atherosclerotic cardiovascular disease (ASCVD) risk score, and the serum levels of neuron-specific enolase (NSE), malondialdehyde (MDA) and calprotectin (Calpro), lipid profile, and random blood glucose level (RBG). RESULTS: After three months, comparing the results of the empagliflozin arm to the control arm showed a significant improvement in the electrophysiological studies and a significant decrease in the BPI-SF score and the mean serum levels of NSE and MDA. However, no significant difference was determined in HbA1c, Calpro, lipid profile, and RBG levels. In addition, the DNS and ASCVD risk scores were not significantly different. The NSE and MDA levels were significantly negatively correlated with the electrophysiological parameters. However, the BPI-SF score showed a non-significant difference. CONCLUSIONS: Empagliflozin may be a promising neuroprotective and therapeutic agent for diabetic peripheral neuropathy. Trial registration Identifier: NCT05977465.

Which field test should be used to compare the functional exercise capacities of patients with type 2 diabetes mellitus with and without diabetic peripheral neuropathy? Cross-sectional study.

BACKGROUND: The 6-minute step test (6MST) has begun to be used as a simple and effective alternative for assessing functional exercise capacity. There is no study using 6MSTs to evaluate the exercise capacities of patients with type 2 diabetes mellitus (DM) with and without diabetic peripheral neuropathy (DPN). OBJECTIVE: To compare the cardiorespiratory responses of the 6-minute walk test (MWT) and the 6MST exercise tests and to analyze the usability of the 6MST in Type 2 DM patients with and without neuropathy. METHODS: 32 non-neuropathic Type 2 DM, 32 neuropathic Type 2 DM patients, and 30 healthy volunteers were included in this cross-sectional study. Functional exercise capacity was evaluated with the 6MWT and the 6MST. The 30-second sit-stand test (30s STS) was used to evaluate general lower extremity muscle strength and function. RESULTS: There was a significant difference in the results of 6MWT (m), 6MST (number of steps), and 30s STS of the three groups (p<0.05). The 6MST results of patients with neuropathic Type 2 DM were significantly lower than those of non-neuropathic diabetics and those who were healthy (number of steps; 114.07±25.57 vs. 133.48±33.57 vs. 160.35±28.52, respectively) (p=0.001). The change in cardiorespiratory response in systolic blood pressure, heart rate, perceived dyspnea, and leg fatigue severity was significantly higher at 6MST than 6MWT in the three groups (p<0.05). 6MST was correlated with 6MWT (r=0.679, p=0.001), and 30s STS (r=0.589, p=0.001) in patients with Type 2 DM. CONCLUSIONS: Cardiorespiratory responses increased more in 6MST compared to 6MWT. In patients with Type 2DM, 6MWT and 6MST were moderately correlated with each other. 6MST is an effective and safe assessment method that may better reveal the differences in functional exercise capacity between neuropathic and non-neuropathic individuals in clinics.

Association of peripheral neuropathy with skeletal muscle mass and function in type two diabetes mellitus patients: A cross-sectional study.

BACKGROUND & OBJECTIVE: Diabetic peripheral neuropathy (DPN) is considered to be a risk factor for development of sarcopenia. Therefore, our study aimed to detect the association between peripheral neuropathy with skeletal muscle mass and function in type two diabetes mellitus (T2DM) patients. METHODS: A total of 176 participants, ≥45 years were included in the study. Out of 176, 60 were healthy volunteers, 60 had T2DM without neuropathy, 56 had T2DM with neuropathy. In all the participants peripheral nerve function was assessed by nerve conduction studies (Common peroneal and Sural nerve) and sarcopenia parameters were evaluated according to the Asian Working Group for Sarcopenia (AWGS) criteria. RESULTS: The present study suggested that diabetic peripheral neuropathy (DPN) was associated with decline in muscle mass, which was found only in men. Our study showed a positive correlation between appendicular skeletal muscle index (ASMI) and common peroneal nerve amplitude and sural nerve amplitude with r=0.527, p<0.05; r=0.847, p<0.001 respectively. Furthermore, in multiple linear regression analyses, we found a positive relationship between ASMI and sural nerve amplitude after adjustment for confounders like age, duration of diabetes, and HbA1C (B=0.739; p<0.001). CONCLUSION: As DPN patients are more prone to developing sarcopenia, and periodic assessment of skeletal muscle mass and function is warranted to initiate early lifestyle interventions in these patients, which will improve their quality of life.

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.

Neuropatía diabética periférica: eficacia clínica de la evaluación semiológica / Diabetic peripheral neuropathy: semiológica clinical efficacy of assessment

El diagnóstico de la Neuropatía Diabética Periférica es tardío. Identificar maniobras semiológicas que permitan el diagnóstico precoz de la neuropatía diabética. Estudio de casos, analítico, transversal y operacional: personas sanas, prediabéticos, diabéticos de reciente diagnóstico y diabéticos de más de 5 años de diagnóstico. Se realizaron 2 evaluaciones: la primera por dos investigadores a ciegas que evaluaron: sensibilidad mecánica, reflejos osteotendinosos y palestesia. También se evaluación de la córnea con Rosa de Bengala y se aplicó el Cuestionario DN4. Segunda Evaluación: von Frey. Biopsia de Piel: será tratada con inmunohistoquímica de campo claro. Muestra de 25 personas. El DN4, obtuvo 14 personas con dolor neuropático. La tinción con Rosa de Bengala obtuvo 7 pacientes con ojo seco y una diabética con más de 5 años de diagnóstico con alteración corneal. En la evaluación con von Frey hubo 3 pacientes con zonas sin respuesta al microfilamento de 10 g. La inmunohistoquímica demostró que el número y densidad de fibras nerviosas tuvo un promedio de 7 fibras/campo en sanos y a partir de los prediabéticos disminuyó desde 4,4 fibras/campo. El ojo seco justifica la evaluación periódica del internista. La evaluación de la sensibilidad con los filamentos de von Frey señala que el monofilamento utilizado individualmente tiene menor eficiencia diagnóstica. La biopsia demostró una capacidad diagnóstica precoz de esta, aún en ausencia de síntomas. La biopsia de piel con cuantificación del número y densidad de fibras, es útil en la identificación temprana de lesión de fibras C y se comporta como método de pesquisa.

The diagnosis of Diabetic Peripheral Neuropathy is made lately. To identify semiological maneuvres that allow early diagnosis of diabetic neuropathy. Case studie, analitic, transversal and operational, without therapeutic intervention in healthy, prediabetic, diabetic and newly diagnosed diabetes over 5 years of diagnosis. The First Assessment was: conducted by two blinded researchers measuring mechanical sensitivity, tendon reflexes, and palesthesia. Von Frey 3) Skin biopsy: the cornea Bengal Rose and DN4 Questionnaire. The second assessment was done with brightfield immunohistochemistry. The sample consisted of 25 persons. The DN4 had 14 people with neuropathic pain. Staining with Rose Bengal scored 7 persons. The second Assessment was done in patients with dry eye and over 5 years of diagnosis of corneal disorder. The evaluation with von Frey 3 patients with no response areas were obtained at 10 g microfilament. Immunohistochemistry showed that the number and density of nerve fibers had an average of 7 fibers in healthy and from prediabetic decreased to 4.4 fibers. The Dry eye justifies the periodic evaluation by the internist. The evaluation of sensitivity with von Frey hairs used indicate that the monofilament has a lower diagnostic efficiency individually. The biopsy revealed an early diagnostic capacity in this condition in the absence of symptoms. Skin biopsy with quantification of the number and density of nerve fibers is useful in early identification of C fiber damage and behaves like screening method.

Avaliação do efeito do transplante de células-tronco mesenquimais derivadas de medula óssea em modelo murino de neuropatia periférica diabética / Evaluation of the effect of mesenchymal stem cells derived from bone marrow transplantation in a murine model of diabetic peripheral neuropathy

O diabetes é uma doença de alta prevalência que, frequentemente, induz o comprometimento do sistema nervoso periférico. Na neuropatia diabética periférica, os sintomas mais encontrados são os sensitivos, no qual a dor neuropática, condição crônica caracterizada por alodinia e hiperalgesia, é a mais debilitante. Esta, prejudica a qualidade de vida do paciente, sendo muitas vezes não responsiva aos métodos farmacológicos convencionais de tratamento. Diante desse panorama, o desenvolvimento de novas abordagens terapêuticas que possuam ação efetiva neste tipo de dor é de grande relevância. O uso da terapia celular no tratamento de lesões do sistema nervoso tem demonstrado resultados promissores e o potencial terapêutico de células-tronco na neuropatia experimental tem sido proposto. Neste estudo, avaliou-se o efeito de células-tronco mesenquimais derivadas da medula óssea (CMsMO) na neuropatia diabética periférica estabelecida em modelo experimental de diabetes induzido por estreptozotocina (ETZ)...

Diabetes is a highly prevalent disease which frequently compromises the peripheral nervous system. In peripheral diabetic neuropathy, the most frequent symptoms are sensitive, in which the neuropathic pain, chronic condition characterized by allodynia and hyperalgesia, is the most debilitating. Neuropathic pain affects the quality of patients’ lives, and is often not responsive to pharmacological conventional treatment methods. Against this background, the development of new therapeutic approaches that have an effective action in this type of pain is of great importance. The use of cell therapy in the treatment of lesions in the nervous system has shown promising results and the therapeutic potential of stem cells in experimental neuropathy has been proposed. In this study, we evaluated the effect of mesenchymal stem cells derived from bone marrow (CMsMO) in peripheral diabetic neuropathy established in experimental model of streptozotocin (STZ) induced diabetes in mice. Four weeks after the induction of the model by administration of STZ...

Análise de fatores associados à ulceração de extremidades em indivíduos diabéticos com neuropatia periférica / Analysis of factors associated with extremity ulceration in diabetic subjects with peripheral neuropathy

A neuropatia periférica é o principal fator de risco para ulceração em pé de indivíduos diabéticos. Este estudo testou a associação de doença arterial periférica (DAP) à ulceração do pé em amostra de pacientes com neuropatia sensório-motora simétrica distal e se marcadores inflamatórios subclínicos também se associariam a esse evento. Foram avaliados 32 indivíduos diabéticos tipo 2 com exame do monofilamento de 10 g alterado, estratificados em 2 grupos segundo a história ou presença de úlcera nas extremidades inferiores. O grupo "com úlcera" (n = 18) incluiu aqueles que apresentavam úlcera ativa ou cicatrizada, ou que tiveram alguma amputação em membro inferior decorrente de complicações da úlcera. Além do exame neurológico e monofilamento, foram submetidos a bioestesiometria, avaliação vascular com Doppler e exames laboratoriais. Os grupos foram semelhantes quanto à distribuição dos sexos, média de idade e tempo de diabetes. O grupo com úlcera apresentou valores médios de altura (1,70 ± 0,06 vs. 1,63 ± 0,11 m; p = 0,044) e limiar de percepção vibratória no maléolo medial (40,9 ± 13,0 vs. 30,6 ± 12,3 V; p = 0,040) mais elevados que o sem a úlcera. Os grupos não diferiram entre si quanto à média dos marcadores inflamatórios. A resposta do reflexo patelar foi também pior no grupo com úlcera (p = 0,047), no qual se observou maior proporção de indivíduos com o índice hálux-braquial alterado (p = 0,030) quando comparado ao sem úlcera. Conclui-se que a DAP está associada à presença de úlcera (atual ou pregressa) em membros inferiores de indivíduos diabéticos neuropatas. A pesquisa de alteração de fluxo de artérias digitais de membro inferior (no hálux) contribuiu para detectar tal associação. Associação de neuropatia ulcerada a marcadores inflamatórios não foi observada, não sendo possível excluí-la devido às limitações do tamanho da amostra. Estudos prospectivos deverão examinar a sensibilidade do índice hálux-braquial...

Peripheral neuropathy is the main risk factor for foot ulceration in diabetic subjects. This study examined the association of peripheral arterial disease (PAD) with foot ulceration in a sample of diabetic subjects with peripheral neuropathy, and also if inflammatory markers would be associated with this event. We evaluated 32 type 2 diabetic individuals with abnormal 10-g monofilament exam, who were stratified in 2 groups according to history or presence of lower extremities ulcer. The group "with ulcer" (n = 18) included the ones that had active or cicatrized ulcer, or some lower-extremity amputation due to ulcer complications. In addition to the neurological examination and monofilament test, they were submitted to biothesiometry, lower extremity vascular assessment with Doppler, and laboratory determinations. No difference between the groups was found concerning sex distribution, mean age, and duration of diabetes diagnosis. The group with ulcer showed higher mean values of height (1.70 ± 0.06 vs. 1.63 ± 0.11 m, p = 0.044), vibration perception threshold measured in medial malleolli (40.9 ± 13.0 vs. 30.6 ± 12.3 V, p = 0.040) than the group without ulcer. The groups did not differ regarding the mean values of the inflammatory markers. Response to patellae reflex was worse in the group with ulcer (p = 0.047), in which a higher proportion of individuals with abnormal toe-brachial index (p = 0.030) was observed as compared to those without ulcer. We concluded that PAD is associated with the presence of ulcer in neuropathic subjects. The assessment of digital arteries flow in lower limbs (in great toe) contributed to detect such association. Association of diabetic foot ulcers and inflammatory markers was not observed, but cannot be excluded due to limitations of sample size. Prospective studies should examine the sensitivity of the toe-brachial index to identify PAD in diabetic individual at risk of ulceration.