RESUMO

Introducción. La pandemia por COVID-19 afectó la atención de pacientes con diabetes mellitus tipo 1 (DM1). Además, se reportó un aumento de cetoacidosis diabética (CAD) como forma de diagnóstico. Objetivos. Evaluar si durante la pandemia por COVID-19 se modificaron el tiempo de evolución de síntomas, las causas de hospitalización por DM1 y la proporción de formas graves, y describir la infección por SARS-CoV-2 en estos pacientes. Población y métodos. Estudio transversal que incluyó pacientes menores de 19 años hospitalizados por DM1 en un centro pediátrico de referencia de marzo de 2018 a agosto de 2019 (prepandemia) y de marzo de 2020 a agosto de 2021 (pandemia). Resultados. Se analizaron 231 internaciones, 135 prepandemia y 96 en pandemia. Los pacientes con debut diabético presentaron menor tiempo de evolución de síntomas en pandemia que en prepandemia (18,8 ± 10,2 vs. 52,1 ±12,1 días, respectivamente; p <0,001). Las hospitalizaciones por todas las formas de debut diabético y el debut con CAD fueron más frecuentes en pandemia que en prepandemia (59,4 % vs. 39,3 %; OR 2,3; IC95% 1,3-3,8; p = 0,003); y (40,6 % vs. 20,7 %; OR 2,6; IC95% 1,4-5,2; p = 0,006) respectivamente. La proporción de formas graves de CAD no se modificó entre ambos períodos (48,1 % vs. 59,9 %; p = 0,3). Solo 6 pacientes presentaron infección por SARS-CoV-2; 3 fueron formas graves. Conclusión. Durante la pandemia, disminuyó el tiempo de evolución de síntomas y aumentó la frecuencia de hospitalizaciones por debut de DM1, con mayor proporción de CAD. No se modificó la proporción de formas graves de CAD

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Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported. Objectives. To assess whether there were changes in the time from symptom onset, the causes of hospitalization due to DM1, and the proportion of severe forms, and to describe SARS-CoV-2 infection in these patients. Population and methods. Cross-sectional study in patients younger than 19 years hospitalized due to DM1 from March 2018 to August 2019 (pre-pandemic) and from March 2020 to August 2021 (pandemic). Results. The assessment included 135 hospitalizations in the pre-pandemic period and 96 during the pandemic. The time from symptom onset during the pandemic in those with debutof diabetes was shorter than in the pre-pandemic period (18.8 ± 10.2 versus 52.1 ± 12.1 days, respectively; p < 0.001). Hospitalizations due to all forms of diabetes debut and debut with DKA were more common during the pandemic than before it (59.4% versus 39.3%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3­3.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.4­5.2; p = 0.006, respectively). Severe forms of DKA did not change between both periods (48.1% versus 59.9%; p = 0.3). Only 6 patients developed SARS-CoV-2 infection; 3 were severe. Conclusion. During the pandemic, the time from symptom onset decreased and the frequency of hospitalizations due to debut of DM1 increased. The proportion of severe forms of DKA did not change.

Assuntos

Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/epidemiologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores de Tempo , Estudos Transversais

RESUMO

ABSTRACT Erectile dysfunction is observed in about 50% of men. It has been found that diabetes mellitus increases its prevalence to 19-86.3%, necessitating attention to a therapeutic strategy. Among the available treatment methods, intracavernosal injections of mesenchymal stem cells have proven to be particularly effective. Objective The purpose of study is to assess and analyse the effectiveness of their use in the treatment of erectile dysfunction in patients with diabetes mellitus. Materials and Methods The literature search was conducted using systematic methods and analysis in databases such as Web of Science, Scopus, PubMed, Elsevier, and Springer, with 41 sources included for further review. Results The study highlights microangiopathic and neuropathic links as key factors in erectile dysfunction development in diabetic patients, stemming from endothelial dysfunction and conductivity disturbances. Mesenchymal stem cell therapy from bone marrow, adipose tissue, and umbilical cord mitigates pathogenic impact through regenerative and anti-apoptotic effects. Due to this, most studies indicate high efficacy of the treatment and rapid therapeutic action through intracavernosal administration. Some studies suggest an increase in the body's receptor sensitivity to other drugs, such as sildenafil. Conclusion From the perspective of further research on this issue, standardising the preparation of stem cells and the treatment method using a large sample size is essential to introduce such a method as an extremely promising therapy for this delicate issue in men into practical medicine. The practical value of the study lies in the systematisation of information on different sources of mesenchymal stem cells for treating erectile dysfunction.

RESUMO

SUMMARY: Marein is a flavonoid compound that reduces blood glucose and lipids and has a protective effect in diabetes. However, the effect and mechanism(s) of marein on renal endothelial-mesenchymal transition in diabetic kidney disease (DKD) have not been elucidated. In this study, single-cell sequencing data on DKD were analyzed using a bioinformation method, and the data underwent reduced dimension clustering. It was found that endothelial cells could be divided into five subclusters. The developmental sequence of the subclusters was 0, 1, 4, 2, and 3, of which subcluster 3 had the most interstitial phenotype.The expression of mesenchymal marker protein:Vimentin(VIM), Fibronectin(FN1), and fibroblast growth factor receptor 1 (FGFR1) increased with the conversion of subclusters. In db/db mice aged 13-14 weeks, which develop DKD complications after 8-12 weeks of age, marein reduced blood levels of glucose, creatinine, and urea nitrogen, improved structural damage in kidney tissue, and reduced collagen deposition and the expression of FN1 and VIM. Marein also up-regulated autophagy marker:Light chain 3II/I(LC3II/I) and decreased FGFR1 expression in renal tissue. In an endothelial-mesenchymal transition model, a high glucose level induced a phenotypic change in human umbilical vein endothelial cells. Marein decreased endothelial cell migration, improved endothelial cell morphology, and decreased the expression of VIM and FN1. The use of the FGFR1 inhibitor, AZD4547, and autophagy inhibitor, 3-Methyladenine(3-MA), further demonstrated the inhibitory effect of marein on high glucose-induced endothelial-mesenchymal transition by reducing FGFR1 expression and up-regulating the autophagy marker protein, LC3II/I. In conclusion, this study suggests that marein has a protective effect on renal endothelial- mesenchymal transition in DKD, which may be mediated by inducing autophagy and down-regulating FGFR1 expression.

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La mareína es un compuesto flavonoide que reduce la glucosa y los lípidos en sangre y tiene un efecto protector en la diabetes. Sin embargo, no se han dilucidado el efecto y los mecanismos de la mareína sobre la transición endotelial- mesenquimatosa renal en la enfermedad renal diabética (ERD). En este estudio, los datos de secuenciación unicelular sobre DKD se analizaron utilizando un método de bioinformación y los datos se sometieron a una agrupación de dimensiones reducidas. Se descubrió que las células endoteliales podían dividirse en cinco subgrupos. La secuencia de desarrollo de los subgrupos fue 0, 1, 4, 2 y 3, de los cuales el subgrupo 3 tenía el fenotipo más intersticial. La expresión de la proteína marcadora mesenquimatosa: vimentina (VIM), fibronectina (FN1) y receptor del factor de crecimiento de fibroblastos. 1 (FGFR1) aumentó con la conversión de subgrupos. En ratones db/db de 13 a 14 semanas de edad, que desarrollan complicaciones de DKD después de las 8 a 12 semanas de edad, la mareína redujo los niveles sanguíneos de glucosa, creatinina y nitrógeno ureico, mejoró el daño estructural en el tejido renal y redujo la deposición y expresión de colágeno de FN1 y VIM. Marein también aumentó el marcador de autofagia: Cadena ligera 3II/I (LC3II/I) y disminuyó la expresión de FGFR1 en el tejido renal. En un modelo de transición endotelial-mesenquimal, un nivel alto de glucosa indujo un cambio fenotípico en las células endoteliales de la vena umbilical humana. Marein disminuyó la migración de células endoteliales, mejoró la morfología de las células endoteliales y disminuyó la expresión de VIM y FN1. El uso del inhibidor de FGFR1, AZD4547, y del inhibidor de la autofagia, 3-metiladenina (3-MA), demostró aún más el efecto inhibidor de la mareína en la transición endotelial-mesenquimal inducida por niveles altos de glucosa al reducir la expresión de FGFR1 y regular positivamente la proteína marcadora de autofagia. , LC3II/I. En conclusión, este estudio sugiere que la mareína tiene un efecto protector sobre la transición endotelial-mesenquimatosa renal en la ERC, que puede estar mediada por la inducción de autofagia y la regulación negativa de la expresión de FGFR1.

Assuntos

Chalconas/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Transição Endotélio-Mesênquima , Autofagia , Biologia Computacional , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos

RESUMO

Introdução:O diabetes mellitus é uma doença metabólica caracterizada pelo controle inadequado dos níveis de glicose no sangue, principalmente um estado crônico de hiperglicemia, causado por diferentes processos patogênicos, levando a complicaçõesdosistema nervoso do diabético queincluem axonopatias, doenças neurodegenerativas, doenças neurovasculares e comprometimento cognitivo geral.Objetivo:Avaliar as complicações clínicas da diabetes tipo 2 em mulheres. Metodologia:Tratou-se de um transversal, do tipo prevalência. Foram usados dois grupos de mulheres, onde todas as mulheres estavam com diagnóstico de diabetes Tipo 2 e idade de 40 e 60 anos, comotratamentooral -G1e com tratamentocominsulinoterapia ­G2,ambosfornecidospelarede pública Para comparação das variáveis estudadas foi utilizado o método de Mann-Whitney, adotando-se o nível de significância menor que 5% (p, valor ,0,05). Resultados:Aproporçãode pessoas com diabetes no Piauí, com consulta e hemoglobina glicada solicitada no primeiro quadrimestre de 2021, 2022, 2023, foi de18, 16 e 34 percentuais,respectivamenteeem Boa Hora nos mesmos quadrimestres foi 36, 39, 56 percentuais, respectivamente.Osprocedimentoshospitalares-por local de residência -Piauí foi de um total de 1.193e em Boa Hora 24. O grupo de mulheres estudadas mostrou uma diferença significativa para a glicemia em jejum e a Hemoglobina glicada quando comparados os grupos G1 e G2. Quase 100% da amostra estava obesa (IMC > 25), não fumava e não praticava atividade física.Conclusões:Concluiu-se que a as pacientes tiveram um agravamento do adoecimento ao longo dos anos com aumento de medicação. A ausência das boas práticas de promoção de saúde, atividade física e alimentação, podem ter contribuídocom o agravamento. Outrossim há necessidade urgente de uma intervenção para mudança de hábitos na população para que a medicalização seja diminuída para a promoção da saúde (AU).

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Introduction: Diabetes mellitus is a metabolic disease characterized by inadequate control of blood glucose levels, mainly a chronic state of hyperglycemia, caused by different pathogenic processes, leading to complications of the nervous system including axonopathies, neurodegenerative diseases,neurovascular diseases and general cognitive impairment.Objective: To evaluate the clinical complications of type 2 diabetes in women.Methodology: This was a cross-sectional, prevalence study.Two groupsof women were used, where all women were diagnosed with Type 2 diabetes and aged between 40 and 60 years, with oral treatment -G1 and treatment with insulin therapy -G2, both provided by the public network .To compare the variables studied, the Mann-Whitney method was used, adopting a significance level of less than 5% (p, value 0.05).Results:The proportion of people with diabetes in Piauí, with consultation and glycated hemoglobin requested in the first four months of 2021, 2022, 2023, was 18, 16 and34 percentages, respectively and in Boa Hora in the same four months it was 36, 39, 56percentages, respectively.SUS hospital procedures -by place of residence -Piauí was a total of 1,193 and in Boa Hora 24. The group of women studied showed a significant difference in fasting blood glucose and glycated hemoglobin when comparing groups G1 and G2.Almost 100% of the sample was obese (BMI > 25), did not smoke and did not practice physical activity.Conclusions: It was concluded that the patients' illness worsened over the years with increased medication.The absence of good health promotion practices, physical activity and nutrition may have contributed to the worsening.Furthermore, there is an urgent need for intervention to change habits in the population so that medicalization is reduced to promote health (AU).

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Introducción: La diabetes mellitus ecaracterizada por un control inadecuado de los niveles de glucosa en sangre, principalmente un estado crónico de hiperglucemia, causado por diferentes procesos patogénicos, derivando en complicaciones del sistema nervioso incluyendo axonopatías, enfermedades neurodegenerativas, enfermedades neurovasculares y deterioro cognitivo general.Objetivo: Evaluar las complicaciones clínicas de la diabetes tipo 2 en mujeres.Metodología: Se trata de un estudio transversal de prevalencia.Se utilizaron dos grupos de mujeres, donde todas fueron diagnosticadas con diabetes tipo 2 y con edades entre 40 y 60 años, con tratamiento oral -G1 y tratamiento con insulinoterapia -G2, ambos prestados por la red pública.Para comparar las variables estudiadas se utilizó el método de Mann-Whitney, adoptando un nivel de significancia inferior al 5% (p, valor 0,05).Resultados:La proporción de personas con diabetes en Piauí, con consulta y hemoglobina glucosilada solicitada en los primeros cuatro meses de 2021, 2022, 2023, fuede 18, 16 y 34 porcentajes, respectivamente y en Boa Hora en los mismos cuatro meses fue de 36 , 39, 56 porcentajes, respectivamente.Los procedimientos hospitalarios del SUS -por lugar de residencia -en Piauí fueron en total 1.193 y en Boa Hora 24. El grupo de mujeres estudiado presentó diferencia significativa en la glucemia en ayunas y en la hemoglobina glucosilada al comparar los grupos G1 y G2.Casi el 100% de la muestra era obesa (IMC > 25), no fumaba y no practicaba actividad física.Conclusiones:Se concluyó que la enfermedad de los pacientes empeoró con el paso de los años con el aumento de la medicación.La ausencia de buenas prácticas de promoción de la salud, actividad física y nutrición puede haber contribuido al empeoramiento.Además, es urgente intervenir para cambiar los hábitos de la población para promover la salud (AU).

Assuntos

Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Doenças Neurodegenerativas/patologia , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/patologia , Hiperglicemia , Hiperglicemia/induzido quimicamente , Estudos Transversais/métodos , Estatísticas não Paramétricas , Diabetes Mellitus/patologia

RESUMO

Anethole is a terpenoid with antioxidant, anti-inflammatory, and neuronal blockade effects, and the present work was undertaken to study the neuroprotective activity of anethole against diabetes mellitus (DM)-induced neuropathy. Streptozotocin-induced DM rats were used to investigate the effects of anethole treatment on morphological, electrophysiological, and biochemical alterations of the sciatic nerve (SN). Anethole partially prevented the mechanical hyposensitivity caused by DM and fully prevented the DM-induced decrease in the cross-sectional area of the SN. In relation to electrophysiological properties of SN fibers, DM reduced the frequency of occurrence of the 3rd component of the compound action potential (CAP) by 15%. It also significantly reduced the conduction velocity of the 1st and 2nd CAP components from 104.6 ± 3.47 and 39.8 ± 1.02 to 89.9 ± 3.03 and 35.4 ± 1.56 m/s, respectively, and increased the duration of the 2nd CAP component from 0.66 ± 0.04 to 0.82 ± 0.09 ms. DM also increases oxidative stress in the SN, altering values related to thiol, TBARS, SOD, and CAT activities. Anethole was capable of fully preventing all these DM electrophysiological and biochemical alterations in the nerve. Thus, the magnitude of the DM-induced neural effects seen in this work, and the prevention afforded by anethole treatment, place this compound in a very favorable position as a potential therapeutic agent for treating diabetic peripheral neuropathy.

Assuntos

Derivados de Alilbenzenos , Anisóis , Diabetes Mellitus Experimental , Estresse Oxidativo , Nervo Isquiático , Animais , Derivados de Alilbenzenos/farmacologia , Nervo Isquiático/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , Anisóis/farmacologia , Anisóis/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Neuropatias Diabéticas/metabolismo , Potenciais de Ação/efeitos dos fármacos , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico

RESUMO

Type 2 diabetes mellitus (T2DM) is a widespread chronic disease characterized by persistent hyperglycemia, leading to severe complications such as diabetic cardiomyopathy and nephropathy, significantly affecting patient health and quality of life. The complex mechanisms underlying these complications include chronic inflammation, oxidative stress, and metabolic dysregulation. Diabetic cardiomyopathy, marked by structural and functional heart abnormalities, and diabetic nephropathy, characterized by progressive kidney damage, are major contributors to the increased morbidity and mortality associated with T2DM. AdipoRon, a synthetic adiponectin receptor agonist, has shown potential in preclinical studies for mimicking the beneficial effects of endogenous adiponectin, reducing inflammation and oxidative stress, and improving lipid metabolism and mitochondrial function. This systematic review evaluates the therapeutic potential of AdipoRon, focusing on its impact on diabetic cardiomyopathy and nephropathy. Through a comprehensive literature search and analysis, we highlight AdipoRon's role in ameliorating cardiovascular and renal complications in various animal models and cellular systems. The findings underscore the urgent need for translational clinical studies to validate AdipoRon's efficacy and safety in human populations, aiming to advance this promising therapeutic approach from experimental models to clinical application, potentially offering new hope for improved management of diabetic complications.

RESUMO

Fomitiporia species have aroused the interest of numerous investigations that reveal their biological activity and medicinal potential. The present investigation shows the antioxidant, anticancer, and immunomodulatory activity of acidic polysaccharides obtained from the fungus Fomitiporia chilensis. The acidic polysaccharides were obtained for acidic precipitation with 2% O-N-cetylpyridinium bromide. Chemical analysis was performed using FT-IR and GC-MS methods. The antioxidant capacity of acidic polysaccharides from F. chilensis was evaluated by scavenging free radicals with an ABTS assay. Macrophage proliferation and cytokine production assays were used to determine the immunomodulatory capacity of the polysaccharides. Anti-tumor and cytotoxicity activity was evaluated with an MTT assay in the U-937, HTC-116, and HGF-1 cell lines. The effect of polysaccharides on the cell cycle of the HCT-116 cell line was determined for flow cytometry. Fourier Transform-infrared characterization revealed characteristic absorption peaks for polysaccharides, whereas the GC-MS analysis detected three peaks corresponding to D-galactose, galacturonic acid, and D-glucose. The secreted TNF-α concentration was increased when the cell was treated with 2 mg mL-1 polysaccharides, whereas the IL-6 concentration was increased with all of the evaluated polysaccharide concentrations. A cell cycle analysis of HTC-116 treated with polysaccharides evidenced that the acidic polysaccharides from F. chilensis induce an increase in the G0/G1 cell cycle phase, increasing the apoptotic cell percentage. Results from a proteomic analysis suggest that some of the molecular mechanisms involved in their antioxidant and cellular detoxifying effects and justify their traditional use in heart diseases. Proteomic data are available through ProteomeXchange under identifier PXD048361. The study on acidic polysaccharides from F. chilensis has unveiled their diverse biological activities, including antioxidant, anticancer, and immunomodulatory effects. These findings underscore the promising therapeutic applications of acidic polysaccharides from F. chilensis, warranting further pharmaceutical and medicinal research exploration.

Assuntos

Antineoplásicos , Antioxidantes , Polissacarídeos Fúngicos , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Animais , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células HCT116 , Citocinas/metabolismo , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Espectroscopia de Infravermelho com Transformada de Fourier , Apoptose/efeitos dos fármacos

RESUMO

Diabetes-related foot osteomyelitis (DFO) is a common yet complex condition, often complicated by concurrent soft tissue infections (STIs). This study evaluates the efficacy of a two-step conservative surgical approach, hypothesizing that it offers comparable outcomes to a one-step procedure. Conducted on a cohort of 93 patients with DFO, the study categorized cases into two types: OM1 (osteomyelitis without STI) and OM2 (osteomyelitis with STI). OM2 was further subdivided into OM2a (early diagnosis) and OM2b (late diagnosis), with OM2 patients undergoing initial soft tissue debridement followed by elective bone surgery. The results indicated no significant differences in infection recurrence or amputation rates between the two surgical approaches, with recurrence observed in 20.7% of cases and amputations in 10.8%. The two-step procedure was associated with higher inflammatory responses and greater need for antibiotics and hospital admissions. However, these factors did not translate into increased recurrence or amputation compared to the one-step procedure. The study supports the two-step approach as a safe and effective method for managing complicated DFO cases, providing a viable alternative to immediate amputation or single-stage surgery. Despite some limitations, including regional specificity and potential underdiagnosis in late-diagnosed cases, the findings offer valuable insights for clinical management and suggest further research to refine treatment protocols. The study's strengths include confirmed histopathological diagnoses and consistent follow-up, reinforcing the validity of the two-step surgical approach for complex DFO treatment.

RESUMO

The aim of this study was to shed light on a crucial issue through a comprehensive evaluation of the cost-effectiveness and cost-utility of a cutting-edge web-based foot-ankle therapeutic exercise program (SOPeD) designed for treating modifiable risk factors for ulcer prevention in individuals with diabetes-related peripheral neuropathy (DPN). In this randomized controlled trial, 62 participants diagnosed with DPN were assigned to the SOPeD software or received usual care for diabetic foot. Primary outcomes were DPN symptoms and severity, foot pain and function, and quality-adjusted life years (QALYs). Between-group comparisons provided 95% confidence intervals. The study also calculated incremental cost-effectiveness and cost-utility ratios (ICERs), analyzed direct costs from a healthcare perspective, and performed a sensitivity analysis to assess uncertainty. The web-based intervention effectively reduced foot pain, improved foot function and showed favorable cost-effectiveness, with ICERs ranging from (USD) $5.37-$148.71 per improvement in different outcomes. There is a high likelihood of cost-effectiveness for improving DPN symptoms and severity, foot pain, and function, even when the minimum willingness-to-pay threshold was set at $1000.00 USD. However, the intervention did not prove to be cost-effective in terms of QALYs. This study reveals SOPeD's effectiveness in reducing foot pain, improving foot function, and demonstrating cost-effectiveness in enhancing functional and clinical outcomes. SOPeD stands as a potential game-changer for modifiable risk factors for ulcers, with our findings indicating a feasible and balanced integration into public health systems. Further studies and considerations are vital for informed decisions to stakeholders and the successful implementation of this preventive program on a larger scale.Trial Registration: ClinicalTrials.gov, NCT04011267. Registered on 8 July 2019.

Assuntos

Análise Custo-Benefício , Pé Diabético , Terapia por Exercício , Humanos , Pé Diabético/prevenção & controle , Pé Diabético/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Terapia por Exercício/economia , Idoso , Anos de Vida Ajustados por Qualidade de Vida , Tornozelo/fisiopatologia , Internet , Resultado do Tratamento , Pé/fisiopatologia

RESUMO

It is well-established that dysfunction of megalin-mediated albumin endocytosis by proximal tubule epithelial cells (PTECs) and the activation of the Renin-Angiotensin System (RAS) play significant roles in the development of Diabetic Kidney Disease (DKD). However, the precise correlation between these factors still requires further investigation. In this study, we aimed to elucidate the potential role of angiotensin II (Ang II), a known effector of RAS, as the mediator of albumin endocytosis dysfunction induced by high glucose (HG) in PTECs. To achieve this, we utilized LLC-PK1 and HK-2 cells, which are well-established in vitro models of PTECs. Using albumin-FITC or DQ-albumin as tracers, we observed that incubation of LLC-PK1 and HK-2 cells with HG (25 mM for 48 h) significantly reduced canonical receptor-mediated albumin endocytosis, primarily due to the decrease in megalin expression. HG increased the concentration of Ang II in the LLC-PK1 cell supernatant, a phenomenon associated with an increase in angiotensin-converting enzyme (ACE) expression and a decrease in prolyl carboxypeptidase (PRCP) expression. ACE type 2 (ACE2) expression remained unchanged. To investigate the potential impact of Ang II on HG effects, the cells were co-incubated with angiotensin receptor inhibitors. Only co-incubation with 10-7 M losartan (an antagonist for type 1 angiotensin receptor, AT1R) attenuated the inhibitory effect of HG on albumin endocytosis, as well as megalin expression. Our findings contribute to understanding the genesis of tubular albuminuria observed in the early stages of DKD, which involves the activation of the Ang II/AT1R axis by HG.

Assuntos

Albuminas , Angiotensina II , Endocitose , Células Epiteliais , Glucose , Túbulos Renais Proximais , Receptor Tipo 1 de Angiotensina , Endocitose/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/efeitos dos fármacos , Angiotensina II/farmacologia , Glucose/metabolismo , Glucose/farmacologia , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Humanos , Albuminas/metabolismo , Suínos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Losartan/farmacologia

RESUMO

INTRODUCTION: Diabetes mellitus is one of the most common diseases worldwide, with a high morbidity and mortality rate. Its prevalence has been increasing, as well as its acute complications, such as hyperglycemic crises. Hyperglycemic crises can present with combined features of diabetic ketoacidosis and hyperosmolar state. However, their implications are not fully understood. OBJECTIVE: To describe the characteristics, outcomes, and complications of the diabetic population with hyperglycemic crises and to value the combined state in the Latin American population. MATERIALS AND METHODS: Retrospective observational study of all hyperglycemic crises treated in the intensive care unit of the Fundación Valle del Lili between January 1, 2015, and December 31, 2020. Descriptive analysis and prevalence ratio estimation for deaths were performed using the robust Poisson regression method. RESULTS: There were 317 patients with confirmed hyperglycemic crises, 43 (13.56%) with diabetic ketoacidosis, 9 (2.83%) in hyperosmolar state, and 265 (83.59%) with combined diabetic ketoacidosis and hyperosmolar state. Infection was the most frequent triggering cause (52.52%). Fatalities due to ketoacidosis occurred in four patients (9.30%) and combined diabetic ketoacidosis/hyperosmolar state in 22 patients (8.30%); no patient had a hyperosmolar state. Mechanical ventilation was associated with death occurrence (adjusted PR = 1.15; 95 % CI 95 = 1.06 - 1.24). CONCLUSIONS: The combined state was the most prevalent presentation of the hyperglycemic crisis, with a mortality rate similar to diabetic ketoacidosis. Invasive mechanical ventilation was associated with a higher occurrence of death.

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Introducción. La diabetes mellitus es una de las enfermedades más frecuentes en todo el mundo, con una tasa elevada de morbimortalidad. Su prevalencia ha ido en aumento y, también, sus complicaciones agudas, como las crisis hiperglucémicas. Las crisis hiperglucémicas pueden presentar características combinadas de cetoacidosis diabética y estado hiperosmolar. Aún no se conocen completamente sus implicaciones. Objetivo. Describir las características, los resultados y las complicaciones de la población diabética con crisis hiperglucémicas, y valorar el estado mixto en la población latinoamericana. Materiales y métodos. Se trata de un estudio observacional retrospectivo de pacientes con crisis hiperglucémicas atendidos en la unidad de cuidados intensivos de la Fundación Valle del Lili, entre el 1º de enero de 2015 y el 31 de diciembre de 2020. Se realizó un análisis descriptivo y se estimó la razón de prevalencia para muerte mediante el método de regresión de Poisson. Resultados. Se incluyeron 317 pacientes con crisis hiperglucémica confirmada, 43 (13,56 %) con cetoacidosis diabética, 9 (2,83 %) en estado hiperosmolar y 265 (83,59 %) en estado mixto. La causa desencadenante más frecuente fue la infección (52,52 %). Cuatro pacientes fallecieron por cetoacidosis (9,30 %), 22 (8,30 %), por un estado mixto; ninguno se encontraba en estado hiperosmolar. La asistencia respiratoria mecánica se asoció con la muerte (razón de prevalencia ajustada = 1,15; IC95%: 1,06-1,24). Conclusiones. El estado combinado fue la presentación más prevalente de la crisis hiperglucémica, con una tasa de mortalidad similar a la de la cetoacidosis diabética, y la asistencia respiratoria mecánica invasiva se asoció con una mayor ocurrencia de muerte.

Assuntos

Cetoacidose Diabética , Hiperglicemia , Humanos , Estudos Retrospectivos , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/complicações , América Latina/epidemiologia , Hiperglicemia/epidemiologia , Hiperglicemia/complicações , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Prevalência , Idoso , Unidades de Terapia Intensiva , Coma Hiperglicêmico Hiperosmolar não Cetótico/epidemiologia , Coma Hiperglicêmico Hiperosmolar não Cetótico/complicações

RESUMO

AIM: To determine the association between atherogenic markers, such as total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL-C), triglycerides/HDL-C ratio (TG/HDL-C), and triglycerides-glucose index (TyG), and the risk of 1-year amputation in adults with diabetic foot in a tertiary level hospital. METHODS: Retrospective cohort study conducted in 162 adult patients with diabetic foot. The outcome was amputation, defined as "primary amputation in patients' clinical history after their first hospitalization due to foot ulcer.". The cutoff point was determined using Youden's J statistic. The relative risk (RR) was presented as an association measure. RESULTS: A TyG index of >9.4 [RR: 1.64 (1.10-2.45)] was associated with a high risk of amputation after 1-year in adults with diabetic foot. However, while a TC/HDL ratio of >4.69 [RR: 1.38 (0.94-2.03)] and a TG/HDL-C ratio > 3.57 [RR: 1.35 (0.89-2.06)] did not show associations with risk of amputation after 1-year. CONCLUSIONS: Only a TyG index of >9.4 was associated with an increased risk of 1-year amputation in adults with diabetic foot. Future studies with larger samples and a longitudinal design may provide more robust evidence and a better understanding of clinical implications.

Assuntos

Amputação Cirúrgica , Biomarcadores , Pé Diabético , Centros de Atenção Terciária , Humanos , Pé Diabético/cirurgia , Pé Diabético/sangue , Pé Diabético/epidemiologia , Amputação Cirúrgica/estatística & dados numéricos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Centros de Atenção Terciária/estatística & dados numéricos , Biomarcadores/sangue , Estudos de Coortes , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/cirurgia , Aterosclerose/complicações , Fatores de Risco , Triglicerídeos/sangue , HDL-Colesterol/sangue , Adulto , Glicemia/análise , Glicemia/metabolismo

RESUMO

Objectives: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus (DM) with symptoms like intense pain and impaired quality of life. This condition has no treatment; instead, the pain is managed with various antidepressants, including duloxetine. The aim of this study is to analyze the evidence on the efficacy of duloxetine in the management of DPN. Methods: A systematic search in different databases was conducted using the keywords "diabetic neuropathy", "duloxetine therapy", "neuropathic pain", and "Diabetes Mellitus". Finally, eight studies were included in this meta-analysis. Results: All articles comparing duloxetine at different doses vs. a placebo reported significant differences in favor of duloxetine on pain scales like 24 h Average Pain Severity (standardized mean difference [SMD] = -1.06, confidence interval [CI] = -1.09 to -1.03, and p < 0.00001) and BPI Severity (SMD = -0.70, CI = -0.72 to -0.68, and p < 0.00001), among others. A total of 75% of the meta-analyses of studies comparing duloxetine at different doses showed a tendency in favor of the 120 mg/d dose. There were significant differences in favor of duloxetine when compared to routine care on the Euro Quality of Life (SMD = -0.04, CI = -0.04 to -0.03, and p < 0.00001) and SF-36 Survey (SMD = -5.86, CI = -6.28 to -5.44, and p < 0.00001) scales. There were no significant differences on the visual analog scale (VAS) when comparing duloxetine and gabapentin. Conclusions: Duloxetine appears to be effective in the management of DPN in different pain, symptom improvement, and quality of life scales.

RESUMO

Diabetes mellitus and its complications are a known public health problem nowadays. Diabetic nephropathy is one of the main complications and the result of multiple mechanisms, including: activation of the renin-angiotensin-aldosterone system, formation of advanced glycation end products and chronic inflammation that led to glomerular and tubulo-interstitial damage producing mesangial expansion and glomerulosclerosis, which finally results in chronic kidney disease. Early detection of diabetic nephropathy is essential for adequate intervention to stop, or at least slow down its progression. Multiple markers have been described, not only the classic ones such as serum creatinine, urea, and albuminuria, but at this point also novel biomarkers such as neutrophil gelatinase-associated lipocalin, tumor necrosis factor 1 receptor and monocyte chemoattractant protein-1, among others. The aim of this article was to provide an update review of the role of biomarkers in the diagnosis of diabetic nephropathy.

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with various complications, including diabetic foot, which can lead to significant morbidity and mortality. Non-healing foot ulcers in diabetic patients are a major risk factor for infections and amputations. Despite conventional treatments, which have limited efficacy, there is a need for more effective therapies. MicroRNAs (miRs) are small non-coding RNAs that play a role in gene expression and have been implicated in diabetic wound healing. miR expression was analyzed through RT-qPCR in 41 diabetic foot Mexican patients and 50 controls. Diabetic foot patients showed significant increases in plasma levels of miR-17-5p (p = 0.001), miR-191-5p (p = 0.001), let-7e-5p (p = 0.001), and miR-33a-5p (p = 0.005) when compared to controls. Elevated levels of miR-17, miR-191, and miR-121 correlated with higher glucose levels in patients with diabetic foot ulcers (r = 0.30, p = 0.004; r = 0.25, p = 0.01; and r = 0.21, p = 0.05, respectively). Levels of miR-17 showed the highest diagnostic potential (AUC 0.903, p = 0.0001). These findings underscore the possible role of these miRs in developing diabetes complications. Our study suggests that high miR-17, miR-191, and miR-121 expression is strongly associated with higher glucose levels and the development of diabetic foot ulcers.

Assuntos

MicroRNA Circulante , Diabetes Mellitus Tipo 2 , Pé Diabético , Humanos , Pé Diabético/sangue , Pé Diabético/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Masculino , Feminino , Pessoa de Meia-Idade , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Idoso , MicroRNAs/sangue , MicroRNAs/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Perfilação da Expressão Gênica

RESUMO

This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM). METHODS: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM. RESULTS: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN. CONCLUSION: The review presents a possible relationship between DPN and CAN, such as in their severity.

Assuntos

Doenças do Sistema Nervoso Autônomo , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/fisiopatologia , Humanos , Diabetes Mellitus Tipo 2/complicações , Doenças do Sistema Nervoso Autônomo/epidemiologia , Doenças do Sistema Nervoso Autônomo/complicações , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/complicações , Cardiomiopatias Diabéticas/diagnóstico , Sistema Nervoso Autônomo/fisiopatologia , Fatores de Risco

RESUMO

Diabetic foot ulcers (DFUs) result in tissue damage or impairment of deeper structures that affect quality of life. The impacts are numerous, and even after a long treatment period, 65% of patients experience recurrence. Among the interventions used to accelerate the healing process of DFUs, photobiomodulation therapy (PBMT) is a painless, noninvasive, and low-cost treatment. To achieve effective therapeutic results optimal PBMT parameters are necessary. The positive effect of PBMT on diabetic cells may be dependent on fluence (J/cm2) and wavelength (nm). This double-blind, randomized clinical trial will be conducted at the University Clinic of Physical Therapy. One hundred patients will be randomly placed in 4 groups. A Laserpulse Ibramed (Helium-Neon, HeNe, 660 nm) with 20 W power will be used (continuous mode), with doses stipulated for each treatment group (GL1, 4 J/cm2; GL2, 8 J/cm2; GL3, 12 J/cm2) and Endophoton KLD GaAs 904 nm (ST, 10 J/cm2) for 2 nonconsecutive days per week for 10 weeks, for a total of 20 sessions. The primary outcomes will be ulcer healing rate and University of Texas classification scores. Patients' DFUs will be assessed on the 1st day, 5 weeks, and 10 weeks of treatment then 1 month after the end of treatment. This study may aid effective clinical decision-making for the management of DFUs.

RESUMO

BACKGROUND: MiRNA-146a and miRNA-223 are key epigenetic regulators of toll-like receptor 4 (TLR4)/tumor necrosis factor-receptor-associated factor 6 (TRAF6)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway, which is involved in diabetic nephropathy (DN) pathogenesis. The currently available oral anti-diabetic treatments have been insufficient to halt DN development and progression. Therefore, this work aimed to assess the renoprotective effect of the natural compound 6-gingerol (GR) either alone or in combination with metformin (MET) in high-fat diet/streptozotocin-induced DN in rats. The proposed molecular mechanisms were also investigated. METHODS: Oral gavage of 6-gingerol (100 mg/kg) and metformin (300 mg/kg) were administered to rats daily for eight weeks. MiRNA-146a, miRNA-223, TLR4, TRAF6, nuclear factor-kappa B (NF-κB) (p65), NLRP3, caspase-1, and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA expressions were measured using real-time PCR. ELISA was used to measure TLR4, TRAF6, NLRP3, caspase-1, tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1ß) renal tissue levels. Renal tissue histopathology and immunohistochemical examination of fibronectin and NF-κB (p65) were performed. RESULTS: 6-Gingerol treatment significantly reduced kidney tissue damage and fibrosis. 6-Gingerol up-regulated miRNA-146a and miRNA-223 and reduced TLR4, TRAF6, NF-κB (p65), NLRP3, caspase-1, TNF-α, IL-1ß, HIF-1α and fibronectin renal expressions. 6-Gingerol improved lipid profile and renal functions, attenuated renal hypertrophy, increased reduced glutathione, and decreased blood glucose and malondialdehyde levels. 6-Gingerol and metformin combination showed superior renoprotective effects than either alone. CONCLUSION: 6-Gingerol demonstrated a key protective role in DN by induction of miRNA-146a and miRNA-223 expression and inhibition of TLR4/TRAF6/NLRP3 inflammasome signaling. 6-Gingerol, a safe, affordable, and abundant natural compound, holds promise for use as an adjuvant therapy with metformin in diabetic patients to attenuate renal damage and stop the progression of DN.

Assuntos

Catecóis , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Dieta Hiperlipídica , Inflamassomos , Metformina , MicroRNAs , Animais , Masculino , Ratos , Catecóis/farmacologia , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Quimioterapia Combinada , Álcoois Graxos/farmacologia , Hipoglicemiantes/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Metformina/farmacologia , Metformina/administração & dosagem , MicroRNAs/metabolismo , MicroRNAs/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Receptor 4 Toll-Like/metabolismo

RESUMO

Chronic kidney disease (CKD) is a growing global public health challenge worldwide. In Mexico, CKD prevalence is alarmingly high and remains a leading cause of morbidity and mortality. Diabetic kidney disease (DKD), a severe complication of diabetes, is a leading determinant of CKD. The escalating diabetes prevalence and the complex regional landscape in Mexico underscore the pressing need for tailored strategies to reduce the burden of CKD. This narrative review, endorsed by the Mexican College of Nephrologists, aims to provide a brief overview and specific strategies for healthcare providers regarding preventing, screening, and treating CKD in patients living with diabetes in all care settings. The key topics covered in this review include the main cardiometabolic contributors of DKD (overweight/obesity, hyperglycemia, arterial hypertension, and dyslipidemia), the identification of kidney-related damage markers, and the benefit of novel pharmacological approaches based on Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA). We also address the potential use of novel therapies based on Mineralocorticoid Receptor Antagonists (MRAs) and their future implications. Emphasizing the importance of multidisciplinary treatment, this narrative review aims to promote strategies that may be useful to alleviate the burden of DKD and its associated complications. It underscores the critical role of healthcare providers and advocates for collaborative efforts to enhance the quality of life for millions of patients affected by DKD.