Hyper-reactive platelets and type 2 diabetes / 中南大学学报(医学版)

Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.

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.

Manejo odontológico del paciente diabético: revisión narrativa / Dental management of the diabetic patient. Narrative review

La diabetes mellitus es una enfermedad metabólica caracterizada por altos niveles de glucosa en sangre y defectos en la producción y/o la acción de la insulina. La hiperglucemia crónica puede derivar en complicaciones metabólicas y vasculares como micro- y macroangiopatías y alteraciones en el metabolismo de lípidos y proteínas. Los pacientes diabéticos mal controlados o no controlados presentan signos y síntomas evidenciables a nivel bucal. En el mundo, alrededor del 8,8% de los adultos de entre 20 y 79 años padecen este trastorno endócrino, y se estima que para el año 2045 unos 629 millones de personas de este rango etario tendrán diabetes. Por ello, es fundamental que el odontólogo se encuentre familiarizado con el manejo médico de estos pacientes, a fin de estar preparado para brindarles un tratamiento adecuado y responder a las emergencias médicas que se presenten durante su atención. En esta revisión se emplearon resultados extraídos manualmente de artículos indexados en las bases de datos MEDLINE y EBSCO que responden a la búsqueda de los términos diabetes mellitus, dental management, oral surgery y HbA1c, con el objetivo de describir el manejo médico-odontológico del paciente diabético hasta la fecha (AU)

Diabetes Mellitus is a metabolic disease characterized by high blood glucose levels and defects in the production and/or the use of insulin. Chronic hyperglycemia can lead to metabolic and vascular complications. Vascular complications include micro and macroangiopathies. The metabolic disorders are: alterations of lipid and protein metabolism. Patients with poorly controlled or uncontrolled diabetes present symptoms that are evident in the oral cavity. Around 8.8% of adults between 20-79 years old, worldwide, have this endocrine disorder and it is estimated that by 2045, 629 million people in this age group, will have diabetes. Therefore, it is essential for dentists to be familiar with the medical management of these patients, in order to provide adequate treatment and eventual management of medical emergencies that may occur during dental treatment. The present review used data extracted manually from articles indexed in the MEDLINE and EBSCO databases, using the terms: Diabetes mellitus, Dental Management, Oral Surgery and HbA1c. The following article aims to describe the medical/dental management of the diabetic patient updated to date (AU)

Prevalência de hiperglicemia de estresse em uma unidade de terapia intensiva / Prevalence of stress hyperglycemia in an intensive care unit

Objetivo: Avaliar a prevalência e o manejo da hiperglicemia de estresse em pacientes internados em uma unidade de terapia intensiva. Métodos: Estudo retrospectivo, realizado de janeiro a junho de 2018. Os dados foram obtidos a partir de 582 prontuá- rios eletrônicos, considerando os valores glicêmicos durante a hospitalização, história prévia ou não de diabetes mellitus, causas do internamento, tempo de permanência na unidade de terapia intensiva, presença de complicações durante o internamento e conduta utilizada em caso de hiperglicemia de estresse. Resulta- dos: Dos 582 pacientes internados na unidade de terapia intensi- va, 579 tiveram sua glicemia indicada nos prontuários analisados; 341 (58,9%) apresentaram hiperglicemia em algum momento da internação, sendo a hiperglicemia de estresse caracterizada em 200 pacientes (35%). A duração média de internamento desses pacientes foi de 8,39±10,9 dias, e a causa mais frequente de inter- namento foi devido a pós-operatório por diversas causas, somando 148 indivíduos (74%). Dentro os pacientes, 72 (36%) apresenta- ram alguma complicação. Além disso, 13 casos (6,5%) evoluíram para óbito. Conclusão: Estudos disponíveis sobre alvos de gli- cose em pacientes críticos das unidades de terapia intensiva apresentam difícil interpretação devido às diferenças subs- tanciais no grupo de populações e aos protocolos de gestão de pacientes utilizados em vários centros. Todavia, a prevalência da hiperglicemia de estresse encontrada nesta amostra é se- melhante à de outras casuísticas estudadas. O índice eleva- do de complicações enfatiza a necessidade de padronização nos critérios para diagnóstico e tratamento da hiperglicemia de estresse objetivando melhor prognóstico desses pacientes independentemente da causa do internamento.

Objective: To evaluate the prevalence and management of stress hyperglycemia in patients hospitalized in anintensive care unit. Methods: Retrospective study, carried out from January to June 2018. Data were obtained from 582 electronic medical records, considering glycemic values during hospitalization, existence of previous history of Diabetes Mellitus, causes of hospitalization, length of stay in the intensive care unit, presence of complications during hospitalization, and behavior used in case of stress hyper- glycemia. Results: Of the 582 patients admitted in the ICU, 579 had their glycemia indicated in the charts analyzed: 341 (58,9%) had hyperglycemia in a certain moment of hospitalization, with stress hyperglycemia being present in 200 patients (35%). The average duration of hospitalization of these patients was 8,39 ± 10,9 days, and the most frequent cause of hospitalization was postoperative for various causes, totaling 148 individuals (74%). Of the patients, 72 (36%) presented some type of complication and 13 patients (6,5%) died. Conclusion: Available studies on glucose targets in critical intensive care unit patients are difficult to be interpre- ted because of substantial differences in the study populations and of patient management protocols used at various centers. However, the prevalence of stress hyperglycemia found in this sample is similar to that of other study groups. The high com- plication rate emphasizes the need for standardization of the criteria for diagnosis and treatment of stress hyperglycemia aiming at a better prognosis of these patients regardless of the cause of hospitalization.

Relationship between Stress Hyperglycemia and Catheter-related Urinary Tract Infection in Stroke Patients / 中国医学科学院学报

Objective To verify the relationship between catheter-related urinary tract infection(CAUTI)and stress hyperglycemia during catheter retention in stroke patients. Methods We used nosocomial infection monitoring system to track the status of CAUTI in stroke patients in a hospital.The study cohort was all the patients who received retention catheterization from January 2016 to March 2020.According to the nested case-control design,multivariate logistic regression analysis was performed to explore the relationship between stress hyperglycemia and CAUTI in stroke patients with indwelling catheter. Results A total of 322 cases of CAUTI and 644 cases of non-CAUTI were enrolled in this study.The length of stay in the case group was(20.68 ± 3.73)d,significantly longer than that[(13.00 ± 4.01)d]in the control group(t=29.473,P <0.001).Compared with non-stress hyperglycemia,stress hyperglycemia posed a higher risk of CAUTI in the stroke patients with indwelling catheter(OR=2.020,95% CI=1.447-2.821,P=0.000)and led to the higher incidence of CAUTI in one thousand days(P<0.001). Conclusion Stress hyperglycemia in the stroke patients with indwelling catheter can significantly increase the risk of CAUTI.

Evaluation of 1, 5 -Anhydroglucitol as a Biomarker for Type 2 Diabetes Mellitus in Patients without Overt Nephropathy

1,5-Anhydroglucitol (1,5-AG) is a non-fasting glycemic marker that responds to hyperglycemia excursions. The reduction in serum levels of 1,5-AG is associated with an increase in postprandial glycemia and glycosuria, phenomena that increase the risk and severity of diabetic complications. The objective is to assess the ability of 1,5-AG to discriminate type 2 diabetes (T2D) patients without overt kidney disease, for screening or diagnostic purposes. The Human Research Ethics Committee of Universidade Federal do Paraná (UFPR) approved the project. Serum samples from 567 individuals classified as healthy subjects (n = 291) and T2D (n = 276) with moderate glycemic control (HbA1c of 7-8%), matched by gender, were analyzed. Serum 1,5-AG levels were measured using an automated enzymatic method (GlycoMark, Inc.). Receiver Operating Characteristic (ROC) curve analysis for 1,5-AG showed sensibility of 65.3% and specificity of 91.1% to detect T2D at cut-off point of 92 µmol/L. The results were similar to the groups' discrimination by glycemia (sensibility/specificity, 62.2%; 89.0%) at cut-off point of 6.3 mmol/L. HbA1c was the best discriminator (sensibility/specificity, 87.4%; 94.2%) at a cut-off point of 5.8% (40 mmol/mol). The serum 1,5-AG concentration was not able to discriminate T2D in the presence of moderate glycemic control with no overt nephropathy.

Diabetes y COVID-19, una relación de ida y vuelta / Diabetes and COVID-19, one relation to go and comeback

Diabetic patients are at risk of developing unfavorably from SARS-COV19 disease, especially when they have poor glycemic control. On the other hand, in the case of diabetic patients with severe COVID, they evolve with severe hyperglycemia, often difficult to manage. Marked hyperglycemia has also been described in people without a known history of previous diabetes, even there have been reported cases of insulin-dependent diabetes debut in days after the disease. The aim of this review is to analyze possible mechanisms involved in the relationship between COVID-19 and DIABETES.

El efecto de los antihiperglicemiantes en los parámetros ecocardiográficos diastólicos y sistólicos / The effect of antihyperglycemic agents on diastolic and systolic echocardiographic parameters

Resumen La enfermedad metabólica diabetes mellitus tipo 2 ocasiona alteraciones en la estructura y en la funcionalidad miocárdica por diferentes mecanismos bioquímicos los cuales pueden ocasionar disfunción diastólica y sistólica, por lo cual el uso de los antihiperglicemiantes aparte de su efecto en la reducción de la hiperglicemia y la hemoglobina glicosilada, algunos han demostrado reducción en la mortalidad cardiovascular y de las hospitalizaciones por insuficiencia cardiaca, basado en estudios clínicos sobre este impacto en el miocardio. También se ha evaluado el efecto de estos fármacos por medio del ecocardiograma transtorácico. El objetivo de este articulo es analizar los valores de los parámetros ecocardiográficos sistólicos y diastólicos en pacientes diabéticos tipo 2 o alguna cardiopatía de base como antecedente de infarto al miocardio e insuficiencia cardiaca con el uso de metformina, sulfonilureas, los inhibidores de la dipeptidilpeptidasa 4 (sitagliptina, alogliptina y linagliptina, vildagliptina), los análogos de GLP1 (liraglutide, albiglutide y exenatide).

Abstract Metabolic disease type 2 diabetes mellitus causes alterations in both structure and myocardial functionality by different biochemical mechanisms which can cause diastolic and systolic dysfunction, which is why the use of antihyperglycemic agents apart from its effect in the reduction of hyperglycemia and glycosylated hemoglobin, some groups have shown reduction in cardiovascular mortality and hospitalizations for heart failure this based on clinical studies, by hypothesis, theories and pleiotropic mechanisms on this impact on the myocardium. On the other hand, the effect of these drugs on the myocardium has also been evaluated by transthoracic echocardiography. Therefore, the aim of this article is to analyze the values of systolic and diastolic echocardiographic parameters in type 2 diabetic patients or some underlying heart disease as a history of myocardial infarction and heart failure with the use of metformin, sulfonylureas, inhibitors of the dipeptidylpeptidase 4 (sitagliptin, alogliptin and linagliptin, vildagliptin), GLP1 analogues (liraglutide, albiglutide and exenatide).

Antioxidant effect of endothelin-1 receptor antagonist protects the rat kidney against chronic injury induced by hypertension and hyperglycemia / Efeito antioxidante de antagonista dos receptores de endotelina-1 protege ratos contra lesão renal crônica induzida por hipertensão e hiperglicemia

ABSTRACT Hypertension and Diabetes mellitus are the two main causes of chronic kidney disease that culminate in the final stage of kidney disease. Since these two risk factors are common and can overlap, new approaches to prevent or treat them are needed. Macitentan (MAC) is a new non-selective antagonist of the endothelin-1 (ET-1) receptor. This study aimed to evaluate the effect of chronic blockade of ET-1 receptor with MAC on the alteration of renal function observed in hypertensive and hyperglycemic animals. Genetically hypertensive rats were divided into control hypertensive (HT-CTL) group, hypertensive and hyperglycemic (HT+DIAB) group, and hypertensive and hyperglycemic group that received 25 mg/kg macitentan (HT-DIAB+MAC25) via gavage for 60 days. Kidney function and parameters associated with oxidative and nitrosative stress were evaluated. Immunohistochemistry for neutrophil gelatinase-associated lipocalin (NGAL), ET-1, and catalase in the renal cortex was performed. The HT+DIAB group showed a decrease in kidney function and an increase in NGAL expression in the renal cortex, as well as an increase in oxidative stress. MAC treatment was associated with attenuated ET-1 and NGAL production and increases in antioxidant defense (catalase expression) and nitric oxide production. In addition, MAC prevented an increase in oxidant injury (as measured by urinary hydroperoxide and lipid peroxidation), thus improving renal function. Our results suggest that the antioxidant effect of the ET-1 receptor antagonist MAC is involved in the improvement of kidney function observed in hypertensive and hyperglycemic rats.

RESUMO Hipertensão e Diabetes Mellitus figuram como as duas principais causas de doença renal crônica que culmina em doença renal terminal. Uma vez que os dois fatores de risco são comuns e podem se sobrepor, novas abordagens preventivas e terapêuticas se fazem necessárias. O macitentan (MAC) é um novo antagonista não-seletivo dos receptores da endotelina-1 (ET-1). O presente estudo teve como objetivo avaliar os efeitos do bloqueio crônico dos receptores da ET-1 com MAC sobre a alteração da função renal em animais hipertensos e hiperglicêmicos. Ratos geneticamente hipertensos foram divididos em grupos com animais hipertensos de controle (HT-CTL), hipertensos e hiperglicêmicos (HT+DIAB) e hipertensos e hiperglicêmicos tratados com 25 mg/kg de macitentan (HT-DIAB+MAC25) via gavagem por 60 dias. Foram avaliados função renal e parâmetros associados ao estresse oxidativo e nitrosativo. Exames de imunoistoquímica foram realizados para lipocalina associada à gelatinase neutrofílica (NGAL), ET-1 e catalase no córtex renal. O grupo HT+DIAB exibiu diminuição da função renal e aumento na expressão de NGAL no córtex renal, bem como estresse oxidativo aumentado. O tratamento com MAC foi associado a atenuação da produção de ET-1 e NGAL e maior ativação das defesas antioxidantes (expressão de catalase) e elevação da produção de óxido nítrico. Além disso, o MAC evitou exacerbação da lesão oxidante (medida por hidroperóxidos urinários e peroxidação lipídica), melhorando assim a função renal. Nossos resultados sugerem que o efeito antioxidante do antagonista dos receptores da ET-1 MAC esteja imbricado no aprimoramento da função renal observada em ratos hipertensos e hiperglicêmicos.

Estudio descriptivo de las cetoacidosis atendidas en urgencias de un hospital de la Comunidad de Madrid mediante la herramienta Savana Manager / Diabetic ketoacidosis in a emergency department of a hospital in Madrid (Spain) using the Savana Manager tool

Objetivo: El objetivo del estudio fue describir las características y evolución de los pacientes que acudieron a las urgencias de nuestro hospital y fueron diagnosticados de cetoacidosis diabética (CAD) utilizando la novedosa herramienta de Big Data Savana. Método: Estudio retrospectivo descriptivo de los pacientes atendidos en urgencias del Hospital Universitario Infanta Leonor durante los años 2011 al 2016 con diagnóstico de CAD. La búsqueda se realizó con Savana Manager. Resultados: Se diagnosticaron 95 episodios de CAD en 68 pacientes. Del total de episodios de CAD, 57 fueron en diabéticos tipo 1 (de ellos 4 LADA), 25 en diabéticos tipo 2, 2 en diabéticos postpancreatectomía y 12 fueron debuts diabéticos. Del total, 61 (64,2%) requirieron ingreso hospitalario, de ellos 23 (24,2%) ingresaron en UCI. La media de HbA1c fue de 10,6 ± 2,1%. Tres pacientes requirieron reingreso tras el alta. La mortalidad fue muy baja con el fallecimiento en 1 paciente diagnosticado simultáneamente de cáncer pulmonar. Los desencadenantes de la CAD fueron: 35 casos (36,8%) falta de adherencia al tratamiento, 31 (32,6%) infecciones, 12 (12,6%) debuts, 8 (8,4%) varias causas y 9 (9,5%) no se pudo determinar la causa. Se clasificaron como CAD de gravedad leve un 28%, un 38% como de gravedad moderada y 34% como graves. La duración del ingreso no se relacionó con la severidad de la cetoacidosis. Conclusiones: La CAD es una complicación grave que afecta tanto a diabéticos tipo 1 como a tipo 2 con elevado porcentaje de ingresos hospitalarios y en UCI, aunque con baja mortalidad en nuestro medio. La duración de los ingresos no se relaciona con la severidad del cuadro.

Objective: the study was designed to describe the clinical features and evolution of the diabetic patients attended in our hospital emergency department with diabetic ketoacidosis (DKA) using the novel Big Data tool Savana. Method: Retrospective descriptive study of the patients attended in the emergency room of the Infanta Leonor University Hospital during the years 2011 to 2016 with diagnosis of CAD. The search was made with Savana. Results: 95 episodes of DKA were diagnosed in 68 patients. Of the total episodes of CAD 57 were in type 1 diabetics (of which 4 were LADA), 25 in type 2 diabetics, 2 in diabetics postpancreatectomy and 12 were new onset of diabetes. Of the total, 61 (64.2%) required hospital admission, of which 23 (24.2%) were admitted to the intensive care unit (ICU). The mean HbA1c was 10.6 ± 2.1%. Three patients required readmission after discharge. Mortality was very low with death in 1 patient simultaneously diagnosed of lung cancer. The triggers of CAD were: 35 cases (36,8%) lack of adherence to treatment, 31 (32.6%) infections, 12 (12.6%) new onset, 8 (8,4%) various causes and 9 (9.5%) the cause could not be determined. They were classified as mild DKA 28%, 38% as moderate and 34% as severe. The duration of admission was not related to the severity of ketoacidosis. Conclusions: DKA is a serious complication that affects both, type 1 and type 2 diabetics patients, with a high percentage of hospital and ICU admissions, although with low mortality in our environment. The lenght of the stay in hospital is not related to the severity of the DKA.

Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

Kidney Disease in Diabetes Mellitus: Cross-Linking between Hyperglycemia, Redox Imbalance and Inflammation / Doença Renal do Diabetes: Cross-Linking entre Hiperglicemia, Desequilíbrio Redox e Inflamação

Abstract Chronic hyperglycemia is the key point of macro- and microvascular complications associated with diabetes mellitus. Excess glucose is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease, which is currently the leading cause of dialysis in the world. The pathogenesis of the disease is complex, multifactorial and not fully elucidated; many factors and mechanisms are involved in the development, progression and clinical outcomes of the disease. Despite the disparate mechanisms involved in renal damage related to diabetes mellitus, the metabolic mechanisms involving oxidative/inflammatory pathways are widely accepted. The is clear evidence that a chronic hyperglycemic state triggers oxidative stress and inflammation mediated by altered metabolic pathways in a self-perpetuating cycle, promoting progression of cell injury and of end-stage renal disease. The present study presents an update on metabolic pathways that involve redox imbalance and inflammation induced by chronic exposure to hyperglycemia in the pathogenesis of diabetic kidney disease.

Resumo A hiperglicemia crônica é o ponto-chave das complicações macro e microvasculares associadas ao diabetes mellitus. O excesso de glicose é responsável por induzir desequilíbrio redox e inflamação sistêmica e intra-renal, desempenhando um papel crítico na patogênese da doença renal do diabetes, configurada atualmente como a principal causa de doença renal dialítica em todo o mundo. A patogênese da doença é complexa, multifatorial e, não totalmente elucidada, estando vários fatores e mecanismos associados ao seu desenvolvimento, progressão e desfechos clínicos. Apesar dos mecanismos díspares envolvidos nos danos renais durante o diabetes, os caminhos metabólicos pela via oxidativa/inflamatória são amplamente aceitos e discutidos. As evidências acentuam que o estado hiperglicêmico crônico desencadeia o estresse oxidativo e a inflamação mediada por diversas vias metabólicas alteradas em um ciclo-vicioso de autoperpetuação, promovendo aumento da injúria celular e progressão para a doença renal dialítica. O presente artigo traz, portanto, uma atualização sobre os caminhos metabólicos que envolvem o desequilíbrio redox e a inflamação induzidos pela exposição crônica à hiperglicemia na patogênese da doença renal do diabetes.

A hiperglicemia altera o perfil inflamatório e imunometabólico de macrófagos derivados de medula óssea de camundongos / Hyperglycemia alters the inflammatory and immunometabolic profile of mouse bone marrow derived macrophages

O diabetes mellitus é um grupo heterogêneo de distúrbios metabólicos caracterizado pela hiperglicemia. Indivíduos diabéticos possuem maior susceptibilidade a infecções comparado a indivíduos sadios e a hiperglicemia é um dos principais fatores que contribuem para isso, em parte, por alterar a resposta imune. Sendo assim, os macrófagos, como células essenciais para a resposta inflamatória, podem apresentar importante papel na resposta imune alterada de indivíduos diabéticos. Neste estudo, investigamos como a hiperglicemia modula os macrófagos derivados da medula óssea (BMDMs) sob um estímulo inflamatório. Para realizar este estudo, os BMDMs de camundongos C57BL/6 machos não diabéticos e diabéticos (60 mg/kg de aloxana, iv) (CEUA / FCF / USP-488) foram cultivados sob condições normais de glicose (5,5 mM) e alta concentração de glicose (25 mM ou 40 mM) e estimuladas ou não com lipopolissacarídeo (LPS, 100 ng/mL). Em comparação com os BMDMs dos camundongos não diabéticos, os BMDMs dos camundongos diabéticos estimulados com LPS apresentaram menor expressão de CD38 no tempo basal e após 24 horas, além de menor expressão de receptor do tipo Toll (TLR)-4 na superfície celular, menor capacidade fagocítica e redução na secreção de óxido nítrico, lactato, fator de necrose tumoral- e interleucina (IL)-10, porém apresentaram maior expressão de CD80, CD86 e MHC-II, maior consumo de oxigênio e maior fosforilação em quinase ativada por estresse/quinase Jun-amino-terminal (SAPK/JNK) subunidade p46 e em quinase regulada por sinal extracelular (ERK) subunidade p42, proteína quinase B (AKT) e proteína quinase C (PKC)-δ assim como maior secreção de IL-6. Quando os BMDMs dos camundongos não diabéticos foram cultivados sob condições de alta concentração de glicose in vitro e estimulados com LPS, a expressão de TLR4 e os níveis de óxido nítrico e peróxido de hidrogênio foram reduzidos. Por outro lado, os BMDMs diabéticos que também foram cultivados em alta concentração de glicose in vitro apresentaram níveis aumentados de lactato e fosforilação reduzida em AKT e PKC-δ, porém apresentaram fosforilação aumentada em p46 SAPK/JNK. A alta concentração de glicose parece modificar o comportamento dos macrófagos, afetando diferentes aspectos dos BMDMs diabéticos e não diabéticos sob estímulo de LPS, assim a hiperglicemia deixa um legado de glicose, induzindo uma memória glicêmica, alterando o estado basal dos macrófagos, modificando a via de sinalização do TLR4 contribuindo para a susceptibilidade de indivíduos diabéticos a infecções

Diabetes mellitus is a heterogeneous group of metabolic disorders characterized by hyperglycemia. Diabetic individuals are more susceptible to infections compared to healthy subjects, and hyperglycemia is one of the major contributing factors, partly because they alter the immune response. Thus, macrophages, as essential cells for the inflammatory response, may play an important role in the altered immune response of diabetic individuals. In this study, we investigated how hyperglycemia modulates bone marrow derived macrophages (BMDMs) under an inflammatory stimulus. To perform this study, BMDMs from non-diabetic male and diabetic C57BL/6 mice (60 mg / kg aloxane, iv) (CEUA / FCF / USP-488) were cultured under normal glucose conditions (5.5 mM) and high glucose concentration (25 mM or 40 mM) and stimulated or not with lipopolysaccharide (LPS, 100 ng / ml). Compared to non-diabetic mice BMDMs, the BMDMs of LPS-stimulated diabetic mice showed lower expression of CD38 at baseline and after 24 hours, as well as lower Toll-like receptor (TLR)-4 on the cell surface, lower secretion of lactate, tumor necrosis factor-, and interleukin (IL)-10, but showed higher expression of CD80, CD86 and MHC-II, higher oxygen consumption and greater phosphorylation in stress-activated kinase/Jun-amino-terminal kinase (SAPK / JNK) p46 subunit and in extracellular signal regulated kinase (ERK) p42 subunit, protein kinase B (AKT) and protein kinase C (PKC)-δ as well as higher secretion of IL-6. When the BMDMs of nondiabetic mice were cultured under conditions of in vitro high glucose concentration and stimulated with LPS, the levels of TLR4 expression, nitric oxide and hydrogen peroxide were reduced. On the other hand, diabetic BMDMs that were also cultured in high glucose concentration of glucose in vitro showed increased levels of lactate and reduced phosphorylation in AKT and PKC-δ, but showed increased phosphorylation in p46 SAPK/JNK. A high glucose concentration seems to modify the behavior of macrophages, affecting different aspects of diabetic and non-diabetic BMDMs under the same LPS stimulus. Hyperglycemia leaves a glucose legacy, inducing a glycemic memory, altering the basal state of macrophages, modifying the TLR4 signaling pathway, and may play a key role in the high susceptibility of diabetic individuals to infections

Mecanismos involucrados en la fragilidad ósea en diabetes mellitus / Mechanisms involved in the bone fragility in diabetes mellitus

La diabetes es una enfermedad crónica asociada con importantes comorbilidades. El sistema esquelético parece ser un objetivo adicional de daño mediado por diabetes. Se acepta que la diabetes tipo 1 y tipo 2 se asocian con un mayor riesgo de fractura ósea. Varios estudios han demostrado que los cambios metabólicos causados por la diabetes pueden influir en el metabolismo óseo disminuyendo la calidad y la resistencia del hueso. Sin embargo, los mecanismos subyacentes no se conocen por completo pero son multifactoriales y, probablemente, incluyen los efectos de la obesidad, hiperglucemia, estrés oxidativo y acumulación de productos finales de glicosilación avanzada. Estos darían lugar a un desequilibrio de varios procesos y sistemas: formación de hueso, resorción ósea, formación y entrecruzamiento de colágeno. Otros factores adicionales como la hipoglucemia inducida por el tratamiento, ciertos medicamentos antidiabéticos con un efecto directo sobre el metabolismo óseo y mineral, así como una mayor propensión a las caídas, contribuirían al aumento del riesgo de fracturas en pacientes con diabetes mellitus. Esta revisión tiene como objetivo describir los mecanismos fisiopatológicas subyacentes a la fragilidad ósea en pacientes diabéticos. (AU)

Diabetes is a chronic disease associated with important comorbidities. The skeletal system seems to be an additional target of diabetes mediated damage. It is accepted that type 1 and type 2 diabetes are associated with an increased risk of bone fracture. Several studies have shown that metabolic changes caused by diabetes can influence bone metabolism by decreasing bone quality and resistance. However, the underlying mechanisms are not completely known but they are multifactorial and probably include the effects of obesity, hyperglycemia, oxidative stress and accumulation of advanced glycosylation end products. These would lead to an imbalance of several processes and systems: bone formation, bone resorption, formation and collagen crosslinking. Other additional factors such as treatment-induced hypoglycemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism, as well as an increased propensity for falls, would contribute to the increased risk of fractures in patients with diabetes mellitus. This review aims to describe the pathophysiological mechanisms underlying bone fragility in diabetic patients. (AU)

Valor pronóstico de los trastornos de la glucemia en la insuficiencia cardíaca congestiva / Prognostic value of glycemia´s disorders in congestive heart failure

Introducción: Existen escasas evidencias de que la glucemia se pueda utilizar para predecir las complicaciones de la insuficiencia cardiaca congestiva. Por esta razón se determinó medir los valores de glucemia de los pacientes con insuficiencia cardiaca congestiva en varios momentos de su ingreso. Objetivo: Identificar el valor pronóstico de los trastornos de la glucemia en la aparición de complicaciones de la insuficiencia cardiaca congestiva. Métodos: Se incluyeron los pacientes ingresados por insuficiencia cardiaca congestiva entre 2013 y 2015, que cumplieran con los criterios de Framingham y no tuvieran tratamientos hiperglucemiantes ni enfermedad terminal. Se les cuantificó glucemia al ingreso, al siguiente día en ayuno y posprandial, y de estar alteradas se realizó hemoglobina glucosilada para determinar si eran diabéticos previos. Se buscó asociación entre la glucemia y las complicaciones intrahospitalarias. Resultados: Se estudiaron 111 pacientes. Las complicaciones más frecuentes fueron los trastornos electrolíticos, la muerte, el shock y el edema pulmonar; los antecedentes patológicos no influyeron en la aparición de complicaciones. Hubo una asociación entre la hiperglucemia intrahospitalaria (p=0,032) y la hiperglucemia de estrés (p=0,035) con la presencia de complicaciones, la hiperglucemia posprandial fue la que mostró una influencia independiente en dicha evolución clínica (p=0,037). Conclusiones: Se encontró una alta frecuencia de hiperglucemia de ingreso, basal y posprandial y una asociación entre la hiperglucemia intrahospitalaria y la posibilidad de complicación durante los períodos de agudización de la insuficiencia cardiaca congestiva(AU)

Introduction: There are scanty evidences that glycemia can be used for predicting the complications of congestive heart failure (CHF). For this reason, it was decided to measure the glycemia values of patients with CHF in several moments of their admission. Objective: To identify the prognostic value of glycemia´s disorders in the appearance of complications of the congestive heart failure. Methods: There were included the patients admitted due to congestive heart failure between 2013 and 2015, who met with Framingham's criteria and had not been under hyperglycaemic treatments nor presenting a terminal illness. Their glycemia was quantified in the admission moment, also the following day in fasting and postprandial, and of being altered a glusocilada hemoglobin´s test was performed to determine if they were diabetics previously. Association between the glycemia and in-hospital complications was looked-up. Results: 111 patients were studied, finding as more frequent complications electrolytic disorders, death, shocks and pulmonary oedema; the pathological background did not have influence in the appearance of complications. There was an association between the in-hospital hyperglycaemia (p=0.032) and the hyperglycaemia due to stress (p=0.035) with the presence of complications, being the posprandial hyperglycaemia the one that showed an independent influence in the above mentioned clinical evolution (p=0.037). Conclusions: There was found a high frequency of hyperglycaemia in the admission moment, as well as basal and postprandial hyperglycaemia; and an association between the in-hospital hyperglycemia and the possibility of complications during the periods of worsening of the CHF(AU)

Investigation of the effect of gestational diabetes on fetal cardiac tissue in streptozotocin induced in rats

Abstract Purpose: To investigate the cause of congenital anomalies resulted from gestational diabetes on fetal cardiac tissue in experimental animal study model. Methods: Totally 12 female Wistar albino rats were divided into two groups, each consisting of 6 rats. Streptozotocin (60 mg/kg) was administered intraperitoneally to the study group by dissolving in citrate solution. The rats with a blood glucose level of 200 mg/dL and above were considered to be diabetic rats. Total antioxidant status (TAS), total oxidative stress (TOS) and oxidative stress index (OSI) values were calculated in the cardiac tissues and maternal serum samples of the fetuses delivered by cesarean section after the mating process. The cardiac tissues were also subjected to histopathological examination. Results: TOS and OSI values in fetal cardiac tissues of the diabetic rats were found to be significantly higher than that of the control group (p=0.026 and p=0.005). Histopathological examination revealed that the mitotic index was lower and the cell organization was found to be damaged in the fetuses of the study group rats. Conclusion: Increased levels of free oxygen radicals considered to be due to hyperglycemia may cause congenital anomalies, especially during organogenesis period, by disrupting cell homeostasis and adversely affecting mitosis.

Ácido úrico como marcador pronóstico de Proteinuria en 24 horas en pacientes diabéticos / Uric acid as a prognostic marker of Proteinuria in diabetic and renal patients

Desde el desarrollo de la Diabetes Mellitus (DM) hasta la aparición de nefropatía transcurren varios años, siendo la albuminuria la primera evidencia de la misma. El Ácido Úrico (AU) parece ser importante en la génesis de nefropatía diabética. Objetivo: Determinar la relación entre niveles séricos de AU y valores de proteinuria en 24 horas en pacientes diabéticos que acudieron a las consultas de Diabetes y Nefrología. Métodos: Estudio de campo, transversal y correlacional. Se determinaron niveles séricos de glicemia, creatinina y AU, además de proteinuria en 24 horas en 94 pacientes, que fueron divididos en 2 grupos: ≤5 años y >5 años de diagnóstico de la DM. Resultados: La edad promedio fue 62,4+ 12,9 años. Predominó el género femenino (69,1%). La DM tipo 2 representó 97,1%. Las complicaciones crónicas más frecuentes fueron las Cardiovasculares (45,7%) y la Nefropatía (30,9%). El valor promedio de Glicemia en ayunas fue 138,1+ 58,5 mg/dl, Creatinina 1,15 + 0,84 mg/dl, AU 4,9+1,8 mg/dl. La mediana de Proteinuria en 24 horas fue 112,1mg/24horas / Varianza (σ) 697872 (mg/24 horas)2. 37, 2% presentó Enfermedad Renal Crónica estadio 2. Se encontró HTA en 72,7% de pacientes con AU elevado. El AU mostró correlación positiva con proteinuria en 24 horas mayor a 150 mg/dl. 4,75 mg/dl funcionó como punto de corte del AU, con 69% de sensibilidad y 69,23% de especificidad. Valores superiores a éste tradujeron 5 veces más riesgo de proteinuria >150 mg/dl. El AU resultó ser un fuerte indicador pronóstico para la aparición de proteinuria(AU)

It often takes several years since the development of Diabetes Mellitus (DM) until the onset of ephropathy, and usually albuminuria is the first clinical evidence of kidney damage. Uric Acid (UA) seems to play an important role in diabetic nephropathy. Objective: To determine the relationship between serum UA and 24-hours Proteinuria in diabetic patients treated on the Diabetes and Nephrology outpatient consultations. Methods: A descriptive cross-sectional correlational study was conducted on 94 patients. Fasting plasma glucose, serum creatinine and UA were determined, as well as 24-hour Proteinuria. Patients were classified into 2 groups: ≤5 years and >5 years since the diagnosis of DM. Results: The mean age was 62, 4+ 12, 9 years. The majority of patients were females (69, 1%). DM2 accounted for 97,1% of all Diabetes types. Cardiovascular diseases (45,7%) and Nephropathy (30,9%) were the most common chronic complications. Fasting plasma glucose mean was 138,1+ 58,5 mg/dl, Creatinine 1,15 + 0,84 mg/dl, UA 4,9+1,8 mg/dl. 24-hours Proteinuria median was 112,1mg/24horas / Variance (σ) 697872 (mg/24- hours) 2. 37,2% showed stage 2 Chronic Kidney Disease. Arterial hypertension was found on 72,7% of the sample with increased UA levels. UA displayed a positive association with 24-hour roteinuria > 150 mg/24 h. 4,75 mg/dl was found as the cut-off point, with sensitivity of 69% and specificity of 69,23%. Subjects with Serum UA above 4,75 mg/dl had a 5 times higher risk of proteinuria>150 mg/dl. Conclusion: UA was a strong prognosis marker for the onset of proteinuria in diabetic patients(AU)