Representaciones sociales sobre diabetes tipo 2 en pacientes del área Metropolitana de Buenos Aires, Argentina

Introducción: Las características y complejidad de la diabetes mellitus tipo 2 motivan la necesidad de un abordaje multi e interdisciplinario. El estudio persigue caracterizar las representaciones sociales de la diabetes mellitus tipo 2 que posee un grupo de pacientes adultos, residentes en Área Metropolitana de Buenos Aires, Argentina Método: Estudio cuantitativo, descriptivo, corte transversal. Se aplicó cuestionario sociodemográfico elaborado ad hoc y técnica de palabras asociadas. Participaron 90 pacientes adultos, reclutados principalmente del servicio de diabetológica del Hospital de Clínicas "José de San Martin" dependiente de la Universidad de Buenos Aires. Resultados: El núcleo de la representación social estuvo integrado por palabras referidas al impacto y malestar emocional que causa esta patología; la identidad de la enfermedad y la necesidad de cuidado de la salud. La periferia contuvo los siguientes temas, de mayor a menor importancia: obesidad, complicaciones de la diabetes, plan alimentario, tratamiento médico y medicación. En menor medida, se mencionaron elementos como actividad física y sedentarismo. De manera tangencial, surgieron los elementos de desinformación y sexualidad. Discusión: La representación social de la diabetes mellitus tipo 2 en pacientes se caracteriza por reflejar, en su núcleo, el temor, impacto y malestar que causa esta enfermedad. La reproducción del discurso médico mediante los temas referidos a factores de riesgo, complicaciones y tratamiento, conforman el sistema periférico de la representación. Elementos importantes tales como actividad física, sedentarismo, desinformación y sexualidad, son poco mencionados. Se destaca la importancia de la salud mental, como una problemática central a abordar en este tipo de patologías. También se sugiere implementación de educación terapéutica.

Introduction: Characteristics and complexity of type 2 diabetes generates the need for a multi and interdisciplinary approach. The aim of the study is to characterize social representations of type 2 diabetes in a group of adult patients, living in the Metropolitan Area of Buenos Aires, Argentina. Method: Descriptive and cross-sectional design. An ad-hoc sociodemographic questionnaire and the associated words technique were applied. 90 adult patients participated, recruited mainly from a diabetes service of a public hospital. Results: The core of the social representation was made up of words referring to the impact and emotional discomfort caused by this pathology, the identity of the disease and the need for health care. The periphery contained the following topics, from most to least important: obesity, diabetes complications, eating plan, medical treatment, and medication. Elements such as physical activity and sedentary lifestyle were mentioned to a lesser extent. Also, misinformation and sexuality were mentioned tangentially. Discussion: Social representation of type 2 diabetes in patients is characterized by reflecting at its core, the fear, impact and discomfort that this disease causes. The reproduction of medical discourse, through topics related to risk factors, complications and treatment, make up the peripheral system of representation. Important elements such as physical activity, sedentary lifestyle, misinformation and sexuality are rarely mentioned. The importance of mental health is highlighted as a central problem to be addressed in this type of pathology. Also, it's suggested the implementation of therapeutic education.

Detección y seguimiento de pacientes según resultados de la prueba de FINDRISK en Atención Primaria

Introducción: la diabetes mellitus es una patología prevalente y por ello la implementación de estrategias prácticas para su diagnóstico son importantes desde la Atención Primaria. Objetivo: determinar los parámetros laboratoriales de los pacientes de la Unidad de Salud Familiar del barrio Chaipe (Encarnación, Paraguay) con moderado a muy alto riesgo de diabetes mellitus tipo 2 según la prueba de FINDRISK. Metodología: estudio prospectivo, observacional, descriptivo, transversal. Se incluyeron pacientes mayores de 18 años que acudieron a consultar en la Unidad de Salud Familiar del barrio Chaipe desde setiembre del 2022 a febrero del 2023. Se aplicó la prueba de FINDRISK para seleccionar a aquellos con moderado a muy alto riesgo de diabetes mellitus tipo 2 para las determinaciones laboratoriales. Resultados: la muestra estuvo conformada por 142 pacientes, con rango de edad menor a 45 años y predominio del sexo femenino. El 42,96 % tenía índice de masa corporal aumentado y 62,68 % circunferencia abdominal de riesgo. El 52,11 % no realizaba actividad física y el 27,46 % no consumía frutas y verduras diariamente. El 25,35 % eran hipertensos, el 11,97 % presentó en alguna oportunidad glicemia elevada y el 56,34 % tenía familiares con diabetes mellitus. El 4,93 % presentó glicemia ≥ 126 mg/dl y el 10,56 % valores de hemoglobina glicosilada (HBA1C) ≥ 6,5 %. El 14,08 % presentó colesterol total ≥ 200 mg/dl y 19,72 % triglicéridos ≥ 150 mg/dl. El 26,65 % presentó 3 o más criterios para síndrome metabólico y se encontró una relación significativa con el riesgo de diabetes mellitus. Conclusiones: se encontró una proporción significativa de pacientes con parámetros laboratoriales de glicemia, HBA1C, colesterol y triglicéridos aumentados.

Introduction: diabetes mellitus is a prevalent pathology and therefore the implementation of practical strategies for its diagnosis are important from Primary Care. Objective: to determine the laboratory parameters of patients from the United Family Healthcare of the Chaipe neighborhood (Encarnación, Paraguay) with moderate to very high risk of diabetes mellitus type 2 according to the FINDRISK test. Methodology: prospective, observational, descriptive, cross-sectional study. Patients over 18 years of age who came to consult at the United Family Healthcare in the Chaipe neighborhood from September 2022 to February 2023 were included. The FINDRISK test was applied to select those with moderate to very high risk of diabetes mellitus type 2 for the laboratory's determinations. Results: the sample was made up of 142 patients, with an age range of less than 45 years and a predominance of the female sex. 42.96 % had an increased body mass index and 62.68 % had an abdominal circumference at risk. 52.11 % did not do physical activity and 27.46 % did not consume fruits and vegetables daily. 25.35 % were hypertensive, 11.97 % had high blood glucose at some point and 56.34 % had family members with diabetes mellitus. 4.93 % had blood glucose ≥ 126 mg/dl and 10.56 % had glycosylated hemoglobin (HBA1C) values ​​≥ 6.5 %. 14.08 % had total cholesterol ≥ 200 mg/dl and 19.72 % had triglycerides ≥ 150 mg/dl. 26.65 % presented 3 or more criteria for metabolic syndrome and a significant relationship was found with the risk of diabetes mellitus. Conclusions: a significant proportion of patients with increased laboratory parameters of glycemia, HBA1C, cholesterol and triglycerides were found.

Características clínicas de pacientes con enfermedad del pie relacionado a la diabetes mellitus que acudieron al Hospital Nacional 2022-2023

Introducción: las enfermedades del pie relacionadas a la diabetes mellitus representan una de las causas de mayor morbilidad e incapacidad en las personas con diabetes mellitus tipo 2, siendo la causa más frecuente de ingreso hospitalario en dicho grupo. Objetivo: describir las características clínicas de los pacientes con enfermedad del pie relacionadas a la diabetes mellitus del Hospital Nacional 2022-2023. Metodología: se seleccionaron 113 pacientes portadores de diabetes mellitus tipo 2 con pie diabético mayores de 18 años. Se evaluaron las variables demográficas, medidas antropométricas, características de la enfermedad, comorbilidades y características clínicas del pie. Resultados: de los 113 estudiados 42 pacientes (37 %) correspondieron al sexo femenino y 71 (63 %) al sexo masculino, promedio de edad fue de 65 años DE 12,191. 75 pacientes (66 %) presentaron pie diabético, con lesión Wagner grado 4. El 81 % (92) tenía hipertensión arterial, sedentarismo 65 % (84), en menor frecuencia pacientes con sobrepeso 38 % (43), obesidad 25 % (38), tabaquismo 23 % (26) y dislipidemia 18 % (20). Conclusión: las características clínicas de los pacientes con diabetes tipo 2 con lesión en el pie coinciden con otros trabajos obtenidos a nivel mundial. Es muy importante prestar atención a este grupo de riesgo, mediante medidas preventivas y realizar el tratamiento precoz para disminuir las complicaciones.

Introduction: foot diseases related to diabetes mellitus represent one of the causes of greatest morbidity and disability in people with type 2 diabetes mellitus, being the most frequent cause of hospital admission in said group. Objective: to describe the clinical characteristics of patients with foot disease related to diabetes mellitus at Hospital Nacional 2022-2023. Methodology: 113 patients with type 2 diabetes mellitus with diabetic foot over 18 years of age were selected. Demographic variables, anthropometric measurements, disease characteristics, comorbidities, and clinical characteristics of the foot were evaluated. Results: of the 113 studied, 42 patients (37 %) were female and 71 (63 %) were male, average age was 65 years SD 12,191. 75 patients (66 %) presented diabetic foot, with Wagner grade 4 lesion. 81 % (92) had high blood pressure, sedentary lifestyle 65 % (84), less frequently overweight patients 38 % (43), obesity 25% (38) ), smoking 23 % (26) and dyslipidemia 18 % (20). Conclusion: the clinical characteristics of patients with type 2 diabetes with foot injury coincide with other works obtained worldwide. It is very important to pay attention to this risk group, through preventive measures and carry out early treatment to reduce complications.

Relación entre índice cintura cadera, índice cintura talla y la Escala FINDRISC en adultos de Guatemala / Relationship between waist-hip index, waist-height index and the FINDRISC Scale in adults from Guatemala

La diabetes mellitus tipo 2 (DM2) es una amenaza para la salud por las complicaciones derivadas de un diagnóstico tardío, donde la identificación oportuna es primordial. Con el objetivo de establecer la relación entre índice cintura talla (ICT), índice cintura cadera (ICC) y puntaje de la escala FINDRISC (Finnish Diabetes Risk Score) como determinantes del riesgo de padecer DM2 a largo plazo, se realizó este estudio predictivo transversal con adultos de 18 y 60 años atendidos en el Centro de Salud Primero de Julio del municipio de Mixco, Guatemala. Participaron 80 adultos, seleccionados por un muestreo aleatorio simple. El instrumento de recolección de datos estuvo conformado por tres secciones: información general de la persona, parámetros antropométricos y la encuesta de FINDRISC. Se generaron modelos lineales generalizados para identificar relaciones entre índice cintura talla (ICT), índice cintura cadera (ICC) y puntaje de la escala FINDRISC (Finnish Diabetes Risk Score). El 36.2% presentó riesgo de desarrollar DM2 a largo plazo; encontrándose un 21.2% en el nivel de riesgo alto y muy alto. Se comprobó que únicamente existe relación significativa entre el ICT y el puntaje de la escala de FINDRISC como determinante del riesgo de padecer DM2 a largo plazo. Se concluye que la implementación de la medición del ICT constituye una herramienta útil para identificar personas con riesgo de desarrollar DM2, siendo su aplicación sencilla, no invasiva, económica y de fácil acceso en los servicios de salud.

Type 2 diabetes mellitus (T2DM) is a health threat due to the complications derived from a late diagnosis, where timely identification is essential. This study aimed to establish the relationship between waist-height index (WHR), waist-hip index (WHR) and the FINDRISC (Finnish Diabetes Risk Score)scale as determinants of the risk of suffering from T2DM in the long term. A cross-sectional predictive study was carried out with a simple random sample of 80 adults between 18 and 60 years old treated at the Primero de Julio Health Center in Mixco, Guatemala. The data collection instrument was structured into three sections: general information, anthropometric parameters and the FINDRISC survey. Generalized linear models were generated to identify relationships between waist-height ratio (WHR), waist-hip ratio (WHR) and the FINDRISC scale score (Finish Diabetes Risk Score). The results shows that 36.2% of the participants were at risk of developing T2DM in the long term; 21.2% being at the high and very high risk level. It was found that there is only a significant relationship between the WHR and the FINDRISC scale score as a determinant of the risk of suffering from T2DM in the long term. The implementation of the waist height index measurement constitutes a useful tool to identify people at risk of developing T2DM, its application being simple, non-invasive, economical and easily accessible in health services.

Interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes / 中国药房

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

Determination and Mechanism Prediction of Potential Active Ingredients in Erdongtang Based on UHPLC-QqQ-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L-1）， baicalin（1 078.37-1 411.52 mg·L-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L-1）， timosaponin BⅡ（245.10-604.89 mg·L-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L-1）， rutin（46.91-1 553.61 mg·L-1）， glycyrrhizic acid（55.97-391.47 mg·L-1）， neomangiferin（37.45-127.03 mg·L-1）， nuciferine（0.89-63.48 mg·L-1）， hyperoside（6.96-136.78 mg·L-1）， liquiritin（30.89-122.78 mg·L-1）， liquiritigenin（26.64-110.67 mg·L-1）， protodioscin（58.57-284.26 mg·L-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L-1）， pseudoprotodioscin（5.49-22.96 mg·L-1）， ginsenoside Rb1（7.31-23.87 mg·L-1）， ginsenoside Rg1（10.78-28.33 mg·L-1）， ginsenoside Re（7.78-24.76 mg·L-1）， ophiopogonin D（2.08-4.29 mg·L-1）， methylophiopogonanone A（0.74-1.67 mg·L-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

Mechanism of Astragaloside Ⅳ on db/db Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Based on AMPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg-1 by gavage， and the metformin group was given 0.067 g·kg-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.

Glucagon-like Peptide-1/Glucose Dependent Insulin Stimulating Polypeptide Double Receptor Agonist-Tirzepatide / 医药导报

Tirzepatide,a new glucagon-like peptide-1/glucose dependent insulin stimulating polypeptide(GLP-1/GIP)double receptor agonist,has been clinically shown to have a strong hypoglycemic effect and a very significant effect on reducing body mass.It can improve insulin sensitivity,and has superior cardiovascular protection and the effect of improving nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH),with few side effects and good compliance.As a dual gut hor-mone agonist,tirzepatide shows strong potential to improve metabolic levels.This article reviews the mechanism of action and clini-cal studies of the GLP-1/GIP dual receptor agonist tirzepatide.

Islet β cell dedifferentiation in pathogenesis of type 2 diabetes / 中国病理生理杂志

Insulin secretion by islet β cells is a fundamental component in glucose homeostasis.Chronic meta-bolic stress causes β cell dysfunction as manifested by reduced cell mass and impaired insulin secretion,which contributes to the pathogenesis of type 2 diabetes(T2D).In the last decade,it has been putatively accepted that β cell dedifferentia-tion is a key pathological mechanism for β cell failure.β cell dedifferentiation is referred as the progressive process that β cells lose their identity and dedifferentiate into non-functional endocrine progenitor-like cells.Typically,aldehyde dehy-drogenase 1 family member A3(ALDH1A3)is a marker of β cell dedifferentiation.Chronic hyperglycemia can lead to de-differentiation of mature β cells,the mechanism of which involves oxidative stress and some key factors.β cell dedifferen-tiation is reversible,therefore,to intervene this process may represent a promising approach to the restoration of β cell function.In this review,we update the recent progress in the pathophysiology of β cell dedifferentiation to provide new strategy for the prevention and treatment of T2D.

Analysis of the Disease Burden of Type 2 Diabetes Attributable to High BMI in China from 1990 to 2019 based on Joinpoint Regression Model / 中国卫生统计

Objective To analyze the disease burden of type 2 diabetes mellitus(T2DM)attributable to high body mass index(BMI)in China from 1990 to 2019 in the context of rapid growth in high BMI rates.Methods Data was extracted from GBD 2019,and the disease burden of T2DM attributable to high BMI in China from 1990 to 2019 was analyzed for overall and subgroups defined by age and sex separately and jointly.The joinpoint regression models were used to analyze the trends of standardized death rate and standardized disability-adjusted life year(DALY)rate.Results From 1990 to 2019,the prevalence of T2DM increased from 2928.78 per 100000 to 6328.79 per 100000 in China.The number of T2DM deaths attributed to high BMI increased from 10500 to 47500 and the standardized death rate increased from 1.25 per 100000 to 2.39 per 100000.The attributed DALY increased from 771800 person-years to 3737600 person-years,and the standardized DALY rate increased from 80.21 per 100000 to 181.54 per 100000.Years of life lost(YLL)and years lived with disability(YLD)and their standardized rates also increased.From 1990 to 2019,the annual average percentage change of the standardized death rate and the standardized DALY rate of T2DM attributable to high BMI were 2.28%and 2.81%,respectively,which were statistically significant(P<0.05)and males were both higher than females.The standardized DALY rate and the standardized death rate of males exceeded that of females in 2010 and 2014,respectively.Age-stratified results showed that the burden of T2DM,which is attributed to a high BMI,is even greater in people over 50 years old.The YLD rate attributable to high BMI increased the most among the 15～49 age group,reaching 323.99%.Conclusion From 1990 to 2019,the disease burden of T2DM that can be attributed to high BMI increased significantly in China.It is necessary to strengthen prevention and control efforts,effectively manage population BMI,and adopt key interventions for high-risk groups to reduce the disease burden of T2DM.

Role of exercise-related irisin in diabetes mellitus and its complications / 中国医科大学学报

Diabetes mellitus is a complex metabolic disease involving multiple organ systems in the body.In recent years,its global incidence rate has increased year by year.In China,the blood glucose control of patients with diabetes mellitus who receive oral hypogly-cemic agents or insulin treatment remains poor.In the early disease stages,exercise is important to control blood glucose levels.Recently,many studies have found that the occurrence of type 2 diabetes mellitus was related to declining levels of irisin,an exercise-related muscle factor.Furthermore,studies have found that irisin improved insulin resistance,promoted the production of pancreatic isletβcells,and affected the body's glucose and lipid metabolism.In addition,its levels were also implicated in the occurrence of various complications,such as diabetic nephropathy and diabetes-related cardiovascular diseases.This article summarizes and analyzes the role of irisin in the occurrence and development of diabetes mellitus and further describes its impact and mechanism on various diabetic complications.

Study on the potential molecular mechanism of Ziyabiti tablets on type 2 diabetes based on network pharmacology / 中国药师

Objective To study the molecular mechanism of Ziyabiti tablets in the treatment of type 2 diabetes(T2DM)by network pharmacology.Methods The chemical components and related targets of Ziyabiti tablets were obtained from TCMSP,ETCM and CNKI,and the targets of T2DM were screened by OMIM and GeneCards databases.The"drug-component-target"network was built by Cytoscape 3.6.1 to screen out the core components and the core targets were screened by protein-protein interaction network.GO functional analysis and KEGG pathway enrichment analysis were performed by DAVID database.Results A total of 144 active components of Ziyabiti tablets were collected in this study,and quercetin,kaempferol,isorhamnetin and so on with higher degree values.There were 823 related targets,of which 700 were related to T2DM,including SRC,MAPK1,MAPK3,etc.GO function analysis suggested that it was related to molecular functions such as signal transduction,protein phosphorylation and protein binding.The main signaling pathways involved in KEGG pathway enrichment analysis were AGE-RAGE signaling pathways in lipid and atherosclerosis,prostate cancer,and diabetic complications.Conclusion Ziyabiti tablets have the characteristics of multi-component,multi-target,and multi-pathway synergistic intervention in the treatment of T2DM,which is mainly composed of quercetin,kaempferol,isorhamnetin and other components to regulate AGE-RAGE signaling pathways through SRC,MAPK1,MAPK3 targets.

Effects of Gegen Qinlian Decoction on PERK/ATF4/CHOP Signaling Pathway in Pancreatic Tissue of Mice with Type 2 Diabetes Mellitus / 中国中医药信息杂志

Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.

Meta-analysis and nursing implications of ketoacidosis caused by sodium-glucose transporter 2 inhibitors / 中华护理杂志

Objective To strengthen nursing awareness and attention,and improve the quality of medication and nursing care,Meta-analysis was used to evaluate the occurrence of sodium-glucose transporter 2 inhibitor related ketoacidosis.Methods Relevant randomized controlled trials were searched in 6 databases,such as CNKI,PubMed,Embase,and the Clinical trial platform,and the literature was screened based on inclusion and exclusion criteria.The search time was from the establishment of databases to January 2023.Revman 5.4.1 was used for quality evaluation and Meta-analysis.Results 24 randomized controlled trials were included.The Meta-analysis results showed that sodium-glucose transporter 2 inhibitors increased the incidence of ketoacidosis(RR=2.52,95％CI[1.82,3.49],P＜0.001).Subgroup analysis showed that the sodium-glucose transporter 2 inhibitors increased the incidence of ketoacidosis in patients with type 2 diabetes(RR=2.42,95％CI[1.70,3.43],P＜0.001),cardiovascular disease(RR=2.32,95％CI[1.59,3.39],P＜0.001),and chronic kidney disease(RR=2.82,95％CI[1.73,4.58],P＜0.001).Cargliflozin(RR=3.21,95％CI[1.43,7.18],P=0.005),Daggliflozin(RR=2.73,95％CI[1.51,4.93],P＜0.001),and Sogliflozin(RR=1.92,95％CI[1.06,3.50],P=0.030)increased the incidence of ketoacidosis,while Engliflozin(RR=1.80,95％CI[0.79,4.11],P=0.160)did not have a significant effect.When the eGFR of patients≤60(mUmin/1.73m2)(RR=2.74,95％CI[1.63,4.60],P＜0.001),the duration of medication≤ 12 month(RR=3.31,95％CI[1.79,6.12],P＜0.001),or the duration of medication＞12 month(RR=2.19,95％CI[1.23,3.91],P=0.008),the sodium-glucose transporter 2 inhibitors increased the occurrence of ketoacidosis.Conclusion For patients receiving sodium-glucose transporter 2 inhibitors treatment regardless of whether they are complicated with diabetes,especially those with heart and kidney diseases,in the early and middle stages of medication,with eGFR ≤60 ml/(min·1.73m2),and those with other susceptibility factors,we should strengthen the observation of patients'medication,optimize medication care,and early identify and intervene in the occurrence of ketoacidosis.

Mechanisms of Shexiang Baoxin Pill in homo-therapy for heteropathy in type 2 diabetes mellitus and coronary heart disease based on network pharmacology / 药学实践与服务

Objective To probe into the mechanism of Shexiang Baoxin Pill in homo-therapy for heteropathy for type 2 diabetes mellitus （T2DM） and coronary heart disease （CHD） based on network pharmacology. Methods All chemical components and action targets of these seven traditional Chinese medical in Shexiang Baoxin Pill were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）, Traditional Chinese Medicines Integrated Database （TCMID）, The Encyclopedia of Traditional Chinese Medicine （ETCM） and BATMAN-TCM platform, and the DisGeNET and GeneCards databases were used to obtain CHD and T2DM-related Disease targets. The “drug-component-target” network map was constructed by Cytoscape 3.8.2 software, the protein-protein interaction （PPI） network map was constructed by STRING database, and the GO biological process analysis and KEGG pathway enrichment analysis were performed on the common targets of Shexiang Baoxin Pill for T2DM and CHD using DAVID online database. Results A total of 101 potential active ingredients for the treatment of T2DM and CHD in Shexiang Baoxin Pill were screened out, corresponding to 229 targets. Network analysis results showed that the common main active ingredients in Shexiang Baoxin Pill for treating T2DM and CHD might be chenodeoxycholic acid, ursodeoxycholic acid, cinnamic aldehyde, bile acids, cinnamic acid, and ginsenosides. The results of pathway enrichment analysis showed that the mechanism of action of Shexiang Baoxin Pill in the treatment of type 2 diabetes and coronary heart disease in treating T2DM and CHD might be related to the inhibition of inflammatory response and oxidative stress. Conclusion Shexiang Baoxin Pill could play a role in treating CHD and T2DM through multiple components, multiple targets and multiple pathways, which provided a certain theoretical basis for the clinical application and further research of Shexiang Baoxin Pill.

Effect of Irisin on islet β cell function in type 2 diabetic rats by regulating autophagy through PI3K/AKT/mTOR pathway / 中国生物制品学杂志

@#Objective To investigate whether Irisin improves islet β cells function in rats with type 2 diabetes mellitus(T2DM)by enhancing autophagy through the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway,so as to provide new ideas for clinical treatment of chronic metabolic diseases such as T2DM and metabolic syndrome.Methods Thirty SD male rats were randomly divided into normal group(NC group),T2DM group,and Irisin intervention group(T2DM + Irisin group). High-fat and high-sugar diet for 5 weeks plus low-dose(35 mg/kg)streptozotocin(STZ)induced T2DM rat model. After 8 weeks of intraperitoneal injection of Irisin,rats were tested for fasting blood glucose(FBG),fasting insulin(FINS),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C). The intraperitoneal glucose tolerance test(IPGTT),intraperitoneal insulin tolerance test(IPITT)and hyperglycemic clamp test were performed to assess the islet function and insulin resistance level of rats in each group. The expression levels of PI3K/AKT/mTOR pathway proteins and autophagyrelated proteins in the pancreas were subsequently detected by Western blot. The expression levels of insulin,microtubuleassociated protein 1 light chain 3(MAP1LC3),p62,and lysosomal associated membrane protein-2(LAMP-2)in rat pancreas were detected by immunohistochemistry(IHC).Results There was an interaction between FBG and intervention time in rats(F = 11. 751,P = 0. 000),and the FBG gradually decreased in the T2DM + Irisin group with the prolongation of the intervention time. From the 4th week of intervention,the FBG in the T2DM + Irisin group decreased significantly compared with that in the T2DM group(F = 1 008. 870,P = 0. 000). Compared with NC group,the serum concentrations of TC,TG,and LDL-C concentrations in the T2DM group significantly increased(each P = 0. 000),while the HDL-C concentrations significantly decreased(P = 0. 000). After Irisin intervention,the above indexes were all improved(P = 0. 010,0. 000,0. 000 and 0. 000,respectively). Western blot results showed that compared with NC group,p62 protein expression and LC3Ⅱ/LC3Ⅰincreased significantly(P = 0. 008 and 0. 048,respectively),and LAMP-2 protein expression decreased significantly(P = 0. 000)in T2DM group. LC3Ⅱ/LC3Ⅰexpression level further increased after Irisin intervention(P =0. 000),but p62 protein level significantly decreased(P = 0. 047)and LAMP-2 protein expression increased significantly(P = 0. 000),and the IHC results were consistent with the Western blot results. The levels of p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR decreased significantly in the T2DM group compared with NC group(P = 0. 006,0. 031 and0. 000,respectively),and the above indicators further decreased after Irisin intervention(P = 0. 033,0. 013 and 0. 000,respectively).Conclusion Irisin can enhance autophagy through PI3K/AKT/mTOR signaling pathway to improve islet βcells function,providing a new idea for the treatment of T2DM.

Analysis of Potential Active Ingredients and Mechanism of Baihu Jia Renshentang in Treatment of Obesity Complicated with Type 2 Diabetes Mellitus / 中国实验方剂学杂志

ObjectiveTo investigate the potential active ingredients and targets of Baihu Jia Renshentang（BHJRST） for the treatment of obesity combined with type 2 diabetes mellitus（T2DM） by network pharmacology and in vivo experiments. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify the material basis of BHJRST. Subsequently， potential targets for the action of the active ingredients were queried in databases such as ChEMBL， Therapeutic Target Database（TTD）， YaTCM， DisGeNET and Traditional Chinese Medicine on Immuno-Oncology（TCMIO）， and the shared targets were identified by taking the intersection of these targets with disease targets. The shared targets were imported into the STRING database to construct a protein-protein interaction（PPI） network， the hub genes were identified by cytoHubba plug-in， and molecular docking was used to validate the binding energy of the hub genes to the bioactive ingredients in BHJRST. Meanwhile， the shared targets were imported into the DAVID platform for gene ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis. The predicted results were subsequently verified by animal experiments. Eighteen 8-week-old male skeletal muscle insulin-like growth factor-1 receptor dysfunction（MKR） mice were induced by a high-fat diet for 12 weeks in order to prepare a mouse model of obesity combined with T2DM. The mice were randomly divided into the model group， metformin group（0.2 g·kg-1） and BHJRST group（27 g·kg-1 in raw material）， and another 6 male FVB mice of the same age as the normal group. The mice in each group were were given the corresponding drugs by gavage， and the normal and model groups were given the same amount of distilled water by gavage， 1 time/d for 6 consecutive weeks. At the end of administration， the body mass， Lee's index， fasting blood glucose（FBG）， oral glucose tolerance test（OGTT） of mice in each group were examined， and the pathological morphology of the white adipose tissue of the epididymis was observed， and the expression of the mRNA of the hub genes in the white adipose tissue of the epididymis was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultA total of 200 bioactive components of BHJRST were identified， of which 64 bioactive components were reverse-matched to 384 targets， and a total of 308 targets were associated with obesity combined with T2DM. Hub genes included mitogen-activated protein kinase 1（MAPK1）， signal transducer and activator of transcription 3（STAT3）， MAPK3， interleukin（IL）-2， Janus kinase 1（JAK1）， nuclear transcription factor-κB p65（RELA）， estrogen receptor 1（ESR1）， transcription factor AP-1（JUN）， MAPK14 and lymphocyte-specific protein tyrosine kinase（LCK）. GO functional annotation showed that it was mainly enriched in cytoplasm， cell membrane and nucleus， and was closely related to important biological processes such as peptide serine phosphorylation， protein phosphorylation and inflammation. In KEGG enrichment analysis， metabolic pathway， lipid and atherosclerosis， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） and MAPK signal pathways were significantly enriched. The molecular docking results showed that the hub genes had a stable binding relationship with 10 bioactive components， including quercetin， isoliquiritigenin， and morin， in BHJRST. The results of animal experiments showed that BHJRST could significantly reduce body mass， Lee's index and FBG levels（P<0.01） in mice with obesity combined with T2DM， improve the pathological changes of white adipose tissue， and down-regulate the the mRNA expression of the hub genes in white adipose tissue of the epididymis（P<0.01）. ConclusionIn this study， 10 potentially active components such as quercetin， isoliquiritigenin， and morin in BHJRST are identified through network pharmacology and animal experiments， and it is possible to treat obesity combined with T2DM by regulating lipid and atherosclerosis， phosphatidylinositol PI3K/Akt and MAPK signal pathways， which provides important clues and theoretical basis for the study of its mechanism and clinical application.

Agmatine ameliorates diabetes type 2-induced nephropathy in rats

@#Objective: To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic nephropathy. Methods: A single dose of streptozotocin (40 mg/kg) coupled with a fructose diet induced diabetes in Wistar rats. Agmatine (40 and 80 mg/kg) was administered to rats for 12 weeks. The body weight and fasting blood glucose were measured weekly. Insulin level, urine output, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C were also determined at the end of the experiment. Furthermore, superoxide dismutase, glutathione, interleukin-1β, interleukin-6, and tumor necrosis factor-alpha were evaluated in kidney tissue. Histopathological study was also performed using hematoxylin and eosin staining. Results: Agmatine at both doses significantly increased final body weight, and lowered fasting blood glucose, urine output, insulin, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C levels compared with the diabetic group (P < 0.05). Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated rats. Moreover, the histopathological changes in renal structure were ameliorated by agmatine treatment. Conclusions: Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative stress. The molecular mechanisms of its nephroprotective actions need to be investigated in future study.

Plant foods intake and risk of type 2 diabetes: Findings from a registry-based prospective cohort study / 环境与职业医学

Background Lifestyle intervention or dietary modification has been the cornerstone of primary prevention and management of type 2 diabetes (T2D). Objective To investigate the associations of plant foods intake with the risk of incident T2D. Methods Based on a general population cohort, the Shanghai Suburban Adult Cohort and Biobank (SSACB), dietary data were collected for each participant in Songjiang District of Shanghai at enrollment with a validated Food Frequency Questionnaire (FFQ), and plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) were calculated. Incident T2D cases were identified according to physician diagnosis (fasting blood glucose ≥7.0 mmol·L−1, or 2 h value during a 75-g oral glucose tolerance test ≥11.1 mmol·L−1, or glycosylated hemoglobin ≥6.5%, or with typical symptoms of hyperglycemia or hyperglycemic crisis, accompanied by a random plasma glucose ≥11.1 mmol·L−1) or medication records, obtained from the electronic information system for residents' medical insurance. Multivariable-adjusted Cox proportional hazards models and restricted cubic splines were used to evaluate the associations of foods from different sources with the risk of incident T2D. Results A total of 29016 participants [age at baseline (55.3±11.6) years] with a median follow-up duration of 5.688 years until 21 September 2022 were included. Plant foods (unprocessed) intake was associated with a decreased risk of incident T2D [HR (95%CI): 0.983 (0.969, 0.998)]. In comparison with participants in the highest quartile (≥859.3 g) of plant foods daily intake, the risk of incident T2D for those in the lowest quartile (<500.9 g) was higher [HR (95%CI): 1.250 (1.012, 1.544)]. No significant associations of animal foods [HR (95%CI): 1.006 (0.987, 1.026)] and processed foods [HR (95%CI): 0.978 (0.944, 1.014)] intakes were found with the risk of incident T2D. Replacing 50 g animal foods [HR (95%CI): 0.982 (0.968, 0.996)] or processed foods [HR (95%CI): 0.983 (0.969, 0.998)] with 50 g plant foods was associated with significantly decreased risks of incident T2D. Additionally, non-linear associations of PDI (Pnonlinear=0.023) and hPDI (Pnonlinear=0.016) with the risk of incident T2D were found in the SSACB. Conclusion Plant foods intake, especially healthful plant foods intake, is significantly associated with a decreased risk of incident T2D.

Effect of Buyang Huanwutang on Skeletal Muscle Injuries in Mouse Model of Type 2 Diabetes Mellitus / 中国实验方剂学杂志

ObjectiveTo study the effects of Buyang Huanwutang on the skeletal muscle injuries in type 2 diabetes mellitus from mitochondrial transport， glucose metabolism， oxidative stress， and inflammation. MethodA total of 60 SPF-grade male C57BL/6J mice were selected in this study. The mouse model of type 2 diabetes mellitus was established with a high-fat diet combined with intraperitoneal injection of streptozotocin. The mice were assigned by the random number table method into blank control， model， high-， medium-， and low-dose （86.5， 43.2， 21.6 g·kg-1， respectively） Buyang Huanwutang， and metformin （150 mg·kg-1） groups， 10 mice in each group. During the experiment period， blood glucose and other indicators of mice were measured regularly. At the end of the experiment， skeletal muscle samples were collected and frozen in 4% paraformaldehyde and -80 ℃， respectively. Blood samples were sent for examination. The skeletal muscle was stained with hematoxylin-eosin. The levels of inflammation indicators and reactive oxygen species （ROS） were determined by enzyme-linked immunosorbent assay. The expression of mitochondrial proteins was determined by Western blot and immunohistochemistry. ResultCompared with the blank control group， the model group showcased increased fasting blood glucose， water intake， and food intake （P<0.01） and decreased body weight （P<0.01）. Compared with the model group， metformin and Buyang Huanwutang reduced the fasting blood glucose， water intake， and food intake （P<0.05， P<0.01） and increased the body weight （P<0.01）. Compared with the blank control group， the model group showed rising levels of tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and ROS （P<0.01）， which were decreased by metformin and Buyang Huanwutang （P<0.05， P<0.01）. The skeletal muscle fibers in the model group were generally atrophic and thin， which suggested atrophy and morphological changes of the skeletal muscle， while metformin and Buyang Huanwutang alleviated the pathological changes of the skeletal muscle and restored the morphology of fiber bundles. Compared with the blank control group， the modeling down-regulated the expression of the mitofusin2 （Mfn2） （P<0.01）， which was up-regulated by metformin and Buyang Huanwutang （P<0.05， P<0.01）. Compared with the blank control group， the modeling up-regulated the expression of the dynamin-related protein （Drp1） （P<0.01）， which were down-regulated by metformin and Buyang Huanwutang （P<0.01）. ConclusionBuyang Huanwutang can improve the body weight and attenuate the pathological changes of the skeletal muscle， reduce fasting blood glucose， food intake， and water intake， lower the levels of TNF-α， IL-6， and ROS， down-regulate the expression of Drp1， and up-regulate the expression of Mfn2 in the mouse model of type 2 diabetes mellitus.