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Autocuidado de los pies en personas con diabetes mellitus tipo 2 atendidas en un hospital público de Chiclayo, 2023Miranda Torres, Lesly Patricia January 2024 (has links)
Las complicaciones del pie diabético son costosas y en gran parte prevenibles a través del autocuidado. Por ello, esta investigación tuvo por objetivo: comprender el autocuidado de los pies en personas con diabetes mellitus tipo 2 atendidas en un hospital público de Chiclayo¿'2023. Esta investigación fue de tipo cualitativa, con un diseño descriptivo. Los sujetos que participaron fueron personas con diabetes mellitus tipo 2 que se atendían en el hospital Las Mercedes y se excluyeron a los que tenían pie diabético o amputación. La muestra fue no probabilística, por conveniencia. El tamaño de la muestra fue delimitado por saturación y redundancia. Para la recolección de datos se utilizó una guía de entrevista semiestructurada, validada por juicios de expertos y prueba piloto. Luego fue aprobada por el Comité de Ética en Investigación de la Facultad de Medicina para la ejecución del proyecto. Se procesaron los datos mediante análisis de contenido temático; así mismo, se aplicaron los criterios de rigor científico y principios éticos de bioética de Sgreccia. Los resultados fueron representados por 5 categorías: a) Hábitos en la revisión, higiene, secado y humectación de los pies, b) Apoyo familiar en el recorte de uñas y las medidas para mejorar la circulación de los pies, c) Uso del calzado adecuado dentro y fuera del hogar según temporada climática y comodidad, d) Costumbres y uso de la medicina tradicional en el autocuidado de los pies, e) Autoaprendizaje y necesidad de educación sanitaria para el autocuidado de los pies. En este estudio, los pacientes diabéticos muestran deficiencias en su autocuidado, como falta de hidratación en los pies. A pesar de algunas prácticas positivas, como la higiene adecuada de pies; la falta de apoyo familiar y la limitada enseñanza del personal de salud contribuyen a prácticas riesgosas. Se destaca la necesidad de proporcionar educación y supervisión para prevenir complicaciones. / Diabetic foot complications are costly and largely preventable through self-care. Therefore, this research aimed to: understand foot self-care in people with type 2 diabetes mellitus treated at a public hospital in Chiclayo, 2023. This research was qualitative, with a descriptive design. The subjects who participated were people with type 2 diabetes mellitus who were treated at the Las Mercedes hospital and those who had diabetic foot or amputation were excluded. The sample was non-probabilistic, for convenience. The sample size was limited by saturation and redundancy. A semi-structured interview guide was used to collect data, validated by expert judgments and pilot testing. It was then approved by the Research Ethics Committee of the Faculty of Medicine for the execution of the project. The data were processed through thematic content analysis; Likewise, the criteria of scientific rigor and ethical principles of Sgreccia bioethics were applied. The results were represented by 5 categories: a) Habits in checking, hygiene, drying and moisturizing the feet, b) Family supportin trimming nails and measures to improve foot circulation, c) Use of appropriate footwear inside and outside the home depending on the weather season and comfort, d) Customs and use of traditional medicine in foot self-care, e) Self-learning and the need for health education for foot self-care. In this study, diabetic patients show deficiencies in their self-care, such as lack of hydration in their feet. Despite some positive practices, such as proper foot hygiene; The lack of family support and the limited teaching of health personnel contribute to risky practices. The need to provide education and supervision to prevent complications is highlighted.
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Patienters upplevelser av egenvård vid diabetes mellitus typ 2 : En litteraturstudie / Patients’ Experiences Of Self-care In Diabetes Mellitus Type 2 : A literature reviewAmini, Nahid, Mowlavi, Violet January 2024 (has links)
Bakgrund: Folksjukdomen diabetes mellitus typ 2 (DMT2) är en kronisk sjukdom som kräver livslång behandling och anses vara ett globalt problem. I Sverige är det cirka 5 procent av befolkningen som har sjukdomen diabetes och en majoritet av dessa har DMT2. Risken för eventuella komplikationer kan minska om personen håller blodsockernivån under kontroll och är följsam i sin egenvård. En fördjupad kunskap om patienters upplevelser av egenvård vid DMT2 möjliggör för sjuksköterskan att erbjuda ett personcentrerat stöd och vägledning relaterat till sjukdomen. Syfte: Syftet med litteraturstudien var att belysa patienters upplevelser av egenvård vid diabetes mellitus typ 2. Metod: Litteraturstudie genomfördes baserad på tio vetenskapliga artiklar med kvalitativ ansats, som kvalitetsgranskades samt analyserades. Artiklarna har hämtats från databaserna Cinahl och PubMed. Resultat: Utifrån analysen kunde tre huvudkategorier och sex underkategorier identifieras. Huvudkategorierna består av Hinder för egenvård, Tillämpning av strategier och Förekomst av förutsättningar. Upplevelserna av egenvård vid DMT2 varierade, och påverkades av faktorer som varierande känslor, kunskapsbrist, kostvanor, fysisk aktivitet, stöd och motivation. Gemensamt för studierna var att personer med DMT2 beskrev olika hinder, strategier och förutsättningar som de upplevde kring sin sjukdom. Konklusion: Det kan antas att sjuksköterskor i mötet med patienter med DMT2, behöver tillämpa ett personcentrerat förhållningssätt inom sitt omvårdnadsarbete, vilket kan ha en direkt påverkan på patienters upplevelser av egenvård. / Background: The endemic disease diabetes mellitus type 2 (DMT2) is a chronic disease that requires lifelong treatment and is considered to be a global issue. Approximately 5 percent of the Swedish population have diabetes, and a majority of these have DMT2. The risk of possible complications can lessen if the person keeps their blood sugar level under control and is compliant in their self-care. An increased knowledge regarding patients’ experiences of self-care in DMT2 enables nurses to offer person-centered support and guidance related to the disease. Aim: The aim of the literature study was to illustrate patients’ experience of self-care in diabetes mellitus type 2. Method: The literature study was based on ten scientific articles with a qualitative approach, that went through quality assessment and was then further analysed. All studies were obtained from the databases Cinahl and PubMed. Results: Based on the analysis, three categories and six subcategories were identified. The three main consist of: Obstacles for self-care, Application of Strategies and Presence of Ideal Circumstances. The experiences of self-care in DMT2 varied and were influenced by factors such as emotions, lack of knowledge, diet, physical activity, support and motivation. The common denominator in the studies was that persons with DMT2 described different obstacles, strategies and ideal circumstances that they experienced regarding their illness. Conclusion: It can be presumed that nurses, in meeting patients with DMT2, need to apply a person-centred approach in their nursing work, which can have a direct impact on patients’ experiences of self-care.
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Effekt av fruktos på utveckling av karies och diabetes mellitus typ 2 : The effect of fructose in the development of dental caries and diabetes mellitus type 2Camay, Fides Mercy, Hosseini, Taraneh January 2023 (has links)
Introduction/Background: Fructose is a monosaccharide that can also be extracted from sugar beet and sugar cane. There are several foods with high fructose content and affect people’s healthy lifestyle. Dental caries is defined as a dental disease caused by bacteria and the presence of fermentable sugars. Diabetes mellitus type 2 previously known as adult-onset diabetes and referred to as non-insulin-dependent diabetes mellitus. It is the most common type of diabetes, accounting for approximately 90-95% of all diabetes cases. Aim: The aim of this study was to investigate fructose's influence and its effect on dental caries and in diabetes mellitus type 2 by answering questions: Does fructose have influence and effect on dental caries? Does fructose have an influence and effect on the plasma glucose in diabetes type 2? Method: The study was a literature review of articles from PubMed, CINAHL and Scopus. The selection process followed three steps and underwent quality reviews. There were 18 articles that were included in the study. Results: The result shows that fructose has some impacts and effects on caries and on plasma glucose. Fructose contributes to the growth of Streptococcus mutans. High intake of fructose increases the risk for diabetes mellitus type 2 and the development of dental caries. Conclusion: When fructose is consumed in large quantities, the caries-causing microorganisms produce acid to such an extent that demineralization of tooth substance can occur. High intake of fructose can also raise the level of plasma glucose and induce fatty liver in diabetes mellitus type 2.
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Egenvård vid diabetes typ 2- En beskrivande litteraturstudie : Personer med diabetes typ 2 erfarenheterSaadoon, Huda, Sundin, Linnea January 2024 (has links)
Bakgrund: Sjuksköterskans specifika kompetens är omvårdnad. Personcentrerad vård fokuserar på att se varje patient som en unik person med individuella behov. Vid diabetes har sjuksköterskan en viktig pedagogisk och handledande funktion för att stärka patientens förmåga att hantera sjukdomen. Sjuksköterskans ansvarsområde vid diabetes består av att ge information och bedöma patientbehov samt ge teoretisk och praktisk utbildning till alla diabetespatienter för att underlätta egenvården. Syfte: Att beskriva personer med diabetes typ 2 erfarenheter av att utföra egenvård. Metod: En beskrivande litteraturstudie innehållande 9 kvalitativa vetenskapliga artiklar. De vetenskapliga artiklarna har hittats eftersökning i databasen PubMed. Huvudresultat: Vid sociala sammanhang förekommer det svårigheter med att hålla sin kost, vilket kan leda till skuldkänslor och bli en psykologisk börda för personer med diabetes typ 2. Flera hinder för egenvård presenterades, alla med påverkan på blodsockernivån. Användning av mobilapp resulterade i att många av användarna lärde sig tolka blodsockervärden och identifiera mönster i aktivitetsnivå, kost och blodsockernivå och samband mellan dem för att kunna hålla blodsockret på en bra nivå. Utbildning är en viktig del i att ändra beteende gällande egenvård. Tillräcklig kunskap om sjukdomen, sekundära sjukdomar och åtgärder för att påverka sjukdomen möjliggör anpassning gällande livsstilen. Slutsats: Sjuksköterskor bör arbeta personcentrerat och för att kunna göra det är det bra att de får en inblick i hur diabetes typ 2 kan påverka personens liv och att det är mer som tillhör egenvård än vad man tänker på när man hör ordet. / Background: The nurse's specific competence is nursing. Person-centered care focuses on seeing each patient as a unique person with individual needs. In the case of diabetes, the nurse has an important educational and supervisory function to strengthen the patient's ability to manage the disease, also providing information and assessing patient needs as well as providing theoretical and practical training to all diabetes patients to facilitate self-care. Purpose: To describe people with diabetes type 2 experience with self-care. Method: A descriptive literature study including 9 qualitative scientific articles. The scientific articles were found through searching the database PubMed. Main result: Social contexts can mean difficulties with maintaining one's diet and feelings of guilt. It is a psychological burden for people with type 2 diabetes. Several barriers to self-care were presented. Using the mobile app resulted in many of the users learning to interpret blood sugar values and identify patterns in activity level, diet and blood sugar level and the relationship between them to keep blood sugar at a satisfactory level. Sufficient knowledge of the disease, secondary diseases, and measures to influence the disease enable adaptation regarding the lifestyle. Conclusion: Nurses should work person-centered and to be able to do that it is good that they get an insight into how diabetes type 2 can affect the person's life and that there is more to self-care then what comes to mind when you hear the word.
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Patienters upplevelser av livsstilsförändringar vid typ 2 diabetes : En litteraturstudie / Patients' Experiences Of Lifestyle Changes In Type 2 Diabetes : A literature reviewFernebrand, Louise, Eksten, Christian January 2024 (has links)
Bakgrund: Antalet personer som lider av typ 2 diabetes växer varje år. Typ 2diabetes är en av de vanligaste kroniska sjukdomarna i världen. Typ 2 diabetes kan också betraktas som en livsstilsrelaterad sjukdom baserad på en ohälsosam livsstil som ökar risken för sjukdom på grund av ohälsosamma matvanor, brist på fysisk aktivitet, stress, sömnbrist och tobaks- och alkoholkonsumtion. Således var livsstilsförändringarna en behandling som skulle kunna hjälpa patienter att förbättra hälsan utan medicinering, samt förbättra livsskvaliteten. Syfte: Litterturstudiens syfte var att belysa patienters upplevelser av lisstilsförändringar vid typ 2 diabetes. Metod: Litterturstudien sammanställde tio vetenskapliga artiklar dör patienters upplevelser av livsstilsförändirngar vid typ 2 diabetes studerats med en kvalitativ metod. Artiklarna hämtades från databaserna Pubmed och Cinahl samt kvalitetsgranskades enligt Statens beredning för medicinsk och social utvärdering. Resultat: De vetenskapliga artiklarna kom från nio länder dör det identifierades fyra huvudteman som presenterades i resultatet: 1) kostens betydelse 2) Den fysiska aktiviitetens betydelse 3) Motivationens betydelse 4) Informationens och kunskapens betydelse. Konklusion: Studien visade att kosten hade ens stor påverkan på patienternas livsstilsförändringar. Att utöva någon form av fysisk aktivitet visade sig också ha en stor inverkan på patientens möjligheter till livsstilsförändring. Den egna motivationen och stöd från familj och sjuksköterskan visade sig vara viktiga komponenter för att lyckas med sin förändring. Slutligen visade studien att patienterna behöver information om diabetes för att framgångsrikt kunna omvandla en ohälsosam livsstil till en hälsosam och få en bättre livskvalitet. / Background: The number of persons suffering from type 2 diabetes is growing annually. Type 2 diabetes is one of the most common chronic diseases globally. Type 2 diabetes can also be considered a lifestyle-related disease based on an unhealthy lifestyle that increases the risk og disease due to unhealthy eating habits, lack of physical activity, stress, lack of sleep, tobacco and alcohol consumption. Thus, lifestyle changes were one of the treatments that could have helped patients improve their health without medicationm as well as improve their quality of life. Aim: The purpose of the literature study was to describe patients´experience of lifestyle changes in type 2 diabetes. Method: The literature study complies ten scientific articals in which the patients´experiences of lifestyle changes in type 2 diabetes were included using a qualitative method. The articles were procured from the database Pubmed and Cinhal and were quality checked according to the Goverment´s preparation for medical and social evaluation. Results: The sciemtific articles were from nine contries where four main themes emerged as presented in the results: 1) Impotance of diet 2) Importance of physical activity 3) Importance of motivation 4) Importance of information and knowledge. Conclusion: The study showed that diet had a significant impact on patients´lifestyle changes. Engaging in some form of physical activity also proved to have a major impact on the patients´ability to change their lifestyle. Self-motivation and support from family and nurses were found to be important components for succsessful change. Finally, the study showed that patients need infromation about diabetes in order to successfully transform an unhealthy lifestyle into a healthy one and have a better quality of life.
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Ispitivanje endotelne disfunkcije i postojanja rezistencije na antitrombocitnu terapiju kod bolesnika sa tipom 2 dijabetes melitusa / Endothelial dysfunction and antiplatelet therapy resistance assessment in patients with type 2 diabetes mellitusMijović Romana 26 September 2016 (has links)
<p>UVOD: Procesi koji obuhvataju endotelnu disfunkciju, oksidativni stres, hroničnu inflamaciju, hiperaktivnost i aktivaciju trombocita te narušavanje ravnoteže procesa koagulacije i fibrinolize od najranijih faza razvoja dijabetes melitusa tip 2 (T2DM) promovišu aterogenezu i nastanak aterotromboznih komplikacija. Kompleksan terapijski pristup u T2DM ima za cilj ne samo uspostavljanje glikoregulacije, korekciju brojnih metaboličkih poremećaja i modifikaciju pridruženih faktora rizika za nastanak ateroskleroze već i primenu antitrombocitne terapije u cilju primarne ili sekundarne prevencije aterotromboznih komplikacija. Uprkos primenjenoj antiagregacionoj terapiji, deo bolesnika doživi rekurentne aterotrombozne atake. Bolesnici sa T2DM se izdvajaju kao grupa sa posebnim rizikom za recidivantne aterotromboze što može biti uslovljeno rezistencijom na primenjenu antitrombocitnu terapiju. Praćenje efekata antitrombocitne terapije i blagovremeno identifikovanje rezistentnih bolesnika ima za cilj optimizaciju primenjene antitrombocitne terapije što može biti od izuzetnog kliničkog značaja u smislu sprečavanja progresije aterotromboznog procesa. CILJ: Proceniti i uporediti nivoe biomarkera, pokazatelja endotelne aktivacije, aktivacije i agregabilnosti trombocita u bolesnika sa bolešću arterijskih krvnih sudova u tipu 2 dijabetes melitusa u odnosu na njihove vrednosti u zdravoj populaciji. Uporediti efikasnost primenjene antitrombocitne terapije tienopiridinima u bolesnika sa tipom 2 dijabetes melitusa i bolešću arterijskih krvnih sudova u odnosu na efikasnost ove terapije u nedijabetičnoj populaciji bolesnika sa bolešću arterijskih krvnih sudova. MATERIJAL I METODE: U ispitivanje je uključeno 100 ispitanika oba pola, starosti od 33 do 70 godina života, kod kojih je prethodno utvrđeno postojanje neke od kliničkih manifestacija bolesti arterijskih krvnih sudova (IBS, CVB, PAB) koji kao antitrombocitnu terapiju uzimaju tienopiridinski preparat, klopidogrel. Od toga, 50 uključenih ispitanika imalo je dijagnozu dijabetes melitus tipa 2, a 50 su bili bolesnici bez dijabetesa. Kontrolnu grupu je činilo 30 klinički i biohemijski zdravih ispitanika, nepušača koji su prema polnoj i dobnoj strukturi odgovarali ispitivanim grupama bolesnika. Svim ispitanicima su urađena antropometrijska merenja, laboratorijska analiza uzoraka krvi na automatizovanim analizatorima sa određivanjem parametara metabolizma glukoze, lipida, parametera inflamacije, KKS, parmetara koagulacije i trombocitnih pokazatelja. Određivanje serumske koncentracije sE–selektina i sP-selektina je vršeno ELISA tehnikom (R&D Systems, Inc. Minneapolis, USA). Plazmatska koncentracija vWFAg-a određivana je imunoturbidimetrijskom metodom na koagulacionom analizatoru Siemens Healthcare Diagnostics, Nemačka. Agregabilnost trombocita je određivana impedantnom agregometrijom (Multiple Electrode Aggregometry - MEA) na Multiplate analizatoru, Dynabyte, Minhen, Nemačka. Bazalna agregabilnost trombocita procenjivana je TRAP testom, rezidualna agregabilnost trombocita pod terapijom klopidogrela ADP testom, rezidualna agregabilnost trombocita pod terapijom aspirina, ASPI testom. Individualni odgovor na primenjenu antiagregacionu terapiju je procenjivan i na osnovu procenta sniženja bazalne agregabilnosti trombocita (%SAT) nakon primenjene antiagregacione terapije što je izračunato sledećim formulama: procena antiagregacionog efekta klopidogrela:%SATadp =100 x (1-ADP/TRAP) i procena antiagregacionog efekta aspirina:%SATaspi =100 x (1-ASPI/TRAP). REZULTATI: Nivo sE-slektina je bio signifikantno viši u bolesnika sa T2DM u odnosu na bolesnike bez dijabetesa (45,1±18,1vs.31,8±10,5ng/ml; p<0,001) i kontrolnu grupu zdravih ispitanika (45,1±18,1vs.27,2±11,2ng/ml; p<0,001). Plazmatski nivo vWF Ag, bio je statistički značajno viši u bolesnika sa T2DM u odnosu na grupu ispitanika bez dijabetesa (172±75,2vs. 146±40,6%; p=0,045), kao i u odnosu na kontrolnu grupu zdravih (172±75,2vs.130±33,8%; p=0,007). Nivo sPselektina bio je statistički značajno viši kod bolesnika s T2DM u odnosu na ispitanike u grupi dijabetesa (95,2±31,8vs.84,0±21,8 ng/ml; p=0,042) i kontrolnoj grupi (95,2±31,8vs.76,7±16,2ng/ml; p=0,004). Uočeno je da je %rP statistički bio značajno viši u grupi dijabetičara u odnosu na grupu ispitanika bez dijabetesa (3,47±1,30vs.2,30±1,30%; p<0,001) i kontrolnu grupu zdravih (3,47±1,30vs.2,29±1,23%; p<0,001). Bolesnici sa T2DM imali su statistički značajno više vrednosti ADP testa (70,3±22,0vs.56,9±19,7U; p=0,002) u odnosu na bolesnike bez dijabetesa, a uočen je i značajno niži stepen procenta sniženja bazalne agregabilnosti, %SATadp, u dijabetičara u odnosu na ispitanike bez dijabetesa (31,6±12,4vs. 48,6±12,6 %; p<0,001). U grupi ispitanika sa T2DM vrednost TRAP testa statistički značajno pozitivno koreliše sa brojem neutrofila (r=0,349;p= 0,013) i NLR-om (r=0,472;p=0,001), a multivarijantnom linearnom regresionom analizom dokazana je nezavisna povezanost TRAP testa i fibrinogena (B=9,61;p=0,009). Takođe, u istoj ispitivanoj grupi postoji pozitivna povezanost ADP testa sa HOMAIR (r=0,319;p=0,024), NLR-om (r=0,515;p<0,001), hsCRP-om (r=0,356;p=0,011), kao i sa %rP (r=0,302;p=0,049). Multivarijantnom linearnom regresionom analizom dokazana je nezavisna povezanost ADP testa i ITM (B=1,43;p=0,043). %SATadp u bolesnika sa T2DM negativno je korelisao sa ITM (r= -0,381;p=0,006), OS (r= - 0,387;p=0,006), HOMA-IR (r= -0,349;p=0,013), hsCRP-om (r= -0,288; p=0,043), %rP (r= -0,302;p=0,049), sE-selektinom (r= -0,369; p=0,008) i sP-selektinom (r= - 0,374;p=0,007). U grupi dijabetičara, postoji pozitivna povezanost %rP sa ITM (r=0,365;p= 0,016), OS (r=0,435;p=0,004), HOMA-IR (r=0,409;p=0,006), hsCRP (r=0,374;p=0,014), sP-selektinom (r=0,341;p=0,025) i vWFAg-om (r=0,348;p=0,022). Takođe, sE-selektin pozitivno koreliše sa ITM (r=0,380;p =0,006), OS (r=0,380; p=0,007), HOMA-IR (r=0,339;p=0,016), hsCRP-om (r=0,351;p=0,013), a sP-selektin sa ITM (r=0,312;p=0,027), OS (r=0,395;p=0,005), HOMA-IR (r=0,286;p=0,044), hsCRP-om (r=0,369; p=0,008) i nivoom sE – selektina (r=0,560;p <0,001). Evaluirajući odgovor na terapiju klopidogrelom u podgrupama bolesnika sa dijabetesom, napravljenim prema kvartilnoj distribuciji nivoa ADP-a, tj. stepenu rezidualne agregabilnosti trombocita u toku terapije klopidogrelom, uočeno je da ukupna bazalna agregabilnost trombocita procenjena TRAP testom statistički značajno raste od prvog do četvrtog kvartila (76,50 ±19,91 vs. 94,54±16,67 vs. 112,00±10,22 vs. 128,92±15,69U;p<0,001), dok se %SATadp od prvog do četvrtog kvartila značajno smanjivao (40,44±13,33 vs. 31,20±11,82 vs. 33,16±7,03 vs. 21,53±10,16%). ZAKLJUČAK: Koncentracije cirkulišućih biomarkera endotelne aktivacije, sE – selektina i vWF Ag-a, solubilnog biomarkera trombocitne aktivacije, sP – selektina, kao i procenat retikulisanih trombocita, %rP, markera trombocitnog prometa, značajno su povišene kod bolesnika sa bolešću arterijskih krvnih sudova u tipu 2 dijabetes melitusa u odnosu na njihove koncentracije kod zdravih ispitanika i bolesnika bez dijabetesa. Bolesnici sa T2DM imali su znatno viši stepen rezistencije na antitrombocitnu terapiju klopidogrelom u odnosu na bolesnike bez dijabetesa, procenjene stepenom rezidualne agregabilnosti trombocita, ADP test, kao i procentom sniženja ukupne bazalne agregabilnosti trombocita, %SATadp, metodom impedantne agregometrije, a što je uslovilo i trend učestalijeg ponavljanja ishemijskih ataka u odnosu na bolesnike bez dijabetesa. Međusobna povezanost ispitivanih biomarkera endotelne i trombocitne aktivacije (sE – selektina, vWF Aga, sP – selektina), kao i markera prometa trombocita (%rP) sa metaboličko inflamatornim parametrima i sa indikatorima odgovora na antiagregacionu terapiju, može ukazivati na to da nepovoljan metabolički milje dijabetičara može biti jedan od doprinosnih faktora lošem odgovoru na antitrombocitnu terapiju klopidogrelom.</p> / <p>INTRODUCTION: Processes involving endothelial dysfunction, oxidative stress, chronic inflammation, platelet activation and the imbalance between coagulation and fibrinolysis promote atherogenesis and atherothrombotic complications at early stage of diabetes mellitus type 2 (T2DM). The complex therapeutic approach in T2DM aims not only to reestablish glycemic control and to correct a number of metabolic disorders, but also to achieve primary or secondary prevention of atherothrombotic complications. Despite the applied antiplatelet therapy, some patients experience recurrent atherothrombotic attacks. Patients with T2DM are the group at particular risk for recurrent atherothrombosis, which can be caused by antiplatelet therapy resistance. Monitoring the effectiveness of antiplatelet therapy and identification of resistant patients aims to optimize the applied antiplatelet therapy, which can be of great clinical significance in terms of preventing progression of atherotrombotic processes. AIM: Evaluate and compare the levels of biomarkers, indicators of endothelial activation, platelet activation and aggregability in patients with arterial vascular disease in type 2 diabetes mellitus compared to their values in a healthy population. Compare the effectiveness of applied antiplatelet therapy with thienopyridines in patients with type 2 diabetes mellitus and arterial vascular disease compared to the efficacy of this therapy in nondiabetic population of patients with arterial vascular disease. MATERIAL AND METHODS: The study included 100 patients, 33 to 70 years of age, with previously established existence of some of the clinical manifestations of arterial vascular disease (CAD, CVD, PAD), taking thienopyridine antiplatelet therapy with clopidogrel. 50 patients was previously diagnosed with diabetes mellitus type 2 and 50 were nondiabetic patients. Control group included 30 age and sex matched healthy participants, non-smokers. All subjects underwent anthropometric measurements and laboratory analysis of blood samples on automated analyzers with determining the parameters of glucose metabolism, lipids, inflammation parameters, complete blood count, coagulation and platelet parameters. Serum concentrations of sEselectin and sP-selectin were determined by ELISA (R&D Systems, Inc., Minneapolis, USA). vWFAg was determined by immunoturbidimetry on coagulometer Siemens Healthcare Diagnostics, Germany. Platelet aggregability was determined by impedance aggregometry (Multiple Electrode Aggregometry - MEA) on Multiplate analyzer, Dynabyte, Munich, Germany. Basal platelet aggregability was estimated by TRAP test, residual platelet aggregability during clopidogrel treatment was estimated by ADP test and during aspirin treatement by ASPI test. Individual response to antiplatelet therapy was estimated by the percentage of decrease in basal platelet aggregability (%DPA) obtained after antiplatelet therapy, calculated bypresented formulas: %DPAadp =100 x (1-ADP/TRAP)and %DPAaspi =100 x (1- ASPI/TRAP). RESULTS: Concentration of sE-selectin was significantly higher in patients with T2DM in order to non-diabetic patients (45,1±18,1vs.31,8±10,5ng/ml;p<0,001) and healthy control group (45,1±18,1vs.27,2±11,2ng/ml; p<0,001). vWF Ag was significantly higher in diabetic patients than in non-diabetics (172±75,2vs. 146±40,6%; p=0,045) and healthy controls (172±75,2vs.130±33,8%; p=0,007). sP-selectin was also significantly higher in patients with T2DM than in non-diabetics (95,2±31,8vs.84,0±21,8 ng/ml; p=0,042) and healthy controls (95,2±31,8vs.76,7±16,2ng/ml; p=0,004). %rP was significantly higher in group of patients with T2DM than in nondiabetic patients (3,47±1,30vs.2,30±1,30%; p<0,001) and healthy control group (3,47±1,30vs.2,29±1,23%; p<0,001). T2DM patients had statistically higher values of ADP test (70,3±22,0vs.56,9±19,7U; p=0,002) compared to patients without diabetes, and significantly lower %DPAadp (31,6±12,4vs. 48,6±12,6 %; p<0,001). In T2DM group of patients, level of TRAP test correlated positively with number of white blood cells (r=0,349;p= 0,013) and NLR (r=0,472;p=0,001), and multivariant linear regression analisys showed significant independent association of TRAP test with fibrinogen (B=9,61;p=0,009). Statistically significant positive correlation of ADP test with HOMA-IR (r=0,319;p=0,024), NLR (r=0,515;p<0,001), hsCRP (r=0,356;p=0,011) and %rP (r=0,302;p=0,049) was observed in patients with T2DM. Multivariant linear regression analisys showed significant independent association of ADP test with BMI (B=1,43;p=0,043). %DPAadp negatively correlated with BMI (r=-0,381;p=0,006), WC (r= - 0,387;p=0,006), HOMA-IR (r= -0,349;p=0,013), hsCRP (r= -0,288; p=0,043), %rP (r= -0,302;p=0,049), sE-selectin (r= -0,369; p=0,008) and sP-selectin (r= -0,374;p=0,007) in diabetic patients. Significant positive correlation of %rP with BMI (r=0,365;p= 0,016), WC (r=0,435;p=0,004), HOMA-IR (r=0,409;p=0,006), hsCRP (r=0,374;p=0,014), sP-selectin (r=0,341;p=0,025) and vWFAg (r=0,348;p=0,022) was found in diabetics. Also, sE-selectin positively correlated with BMI (r=0,380;p =0,006), WC (r=0,380; p=0,007), HOMA-IR (r=0,339;p=0,016), hsCRP(r=0,351;p=0,013), and sPselectin correlated positively with BMI (r=0,312;p=0,027), WC (r=0,395;p=0,005), HOMA-IR (r=0,286;p=0,044), hsCRP (r=0,369; p=0,008) and sE – selectin (r=0,560;p <0,001). Evaluating the response to clopidogrel therapy in subgrpoups of diabetic patients accoarding the quartile distribution of ADP test (clopidogrel on-treatment platelet reactivity), it is found that total basal aggregability estimated by TRAP test significantly increased from the first to the fourth quartile (76,50 ±19,91 vs. 94,54±16,67 vs. 112,00±10,22 vs. 128,92±15,69U;p<0,001) while %DPAadp decreased (40,44±13,33 vs. 31,20±11,82 vs. 33,16±7,03 vs. 21,53±10,16%). CONCLUSION: Concentration of circulating biomarkers of endothelial activation, sE-selectin and vWF Ag, soluble marker of platelet activation, sP – selectin, as well as percentage of reticulated platelets, %rP, marker of platelet turnover, were significantly higher in patients with arterial vascular disease in T2DM compared to healthy controls and non-diabetics. Patients with T2DM had significantly higher degree of resistance to antiplatelet therapy with clopidogrel compared to non diabetics, estimated by ADP test, as well as with %DPAadp, what caused more frequent recurrent ischemic attacks compared to nondiabetic patients. Correlation of biomarkers of endothelial and platelet activation (sE – selectin, vWF Ag, sP – selectin) and markers of platelet turnover (%rP) with metabolic profile indicators and poor antiplatelet therapy response suggest that altered metabolic profile can be one of contributing factors of poor antiplatelet response in diabetic patients.</p>
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Značaj adiponektina u proceni kardiometaboličkog profila i rizika za razvoj tipa 2 šećerne bolesti kod gojaznih osoba / The significance of adiponectin in the assessment of cardiometabolic profile and of risk of type 2 diabetes development in obese personsPopović Đorđe 29 December 2016 (has links)
<p>Gojaznost se najčešće definiše kao uvećanje udela masne mase u ukupnoj telesnoj masi. Danas gojaznost poprima pandemijske razmere i karakter globalnog zdravstveno-socijalnog problema jer predstavlja faktor rizika za razvoj masovnih nezaraznih bolesti, pre svega tipa 2 šećerne bolesti (T2DM) i kardiovaskularnih bolesti. Adipokini su molekule koje luči masno tkivo i koji imaju značajnu ulogu u regulaciji mnogobrojnih procesa u ljudskom organizmu. Adiponektin (ADN) je adipokin sa antidijabetogenim, antiinflamatornim i antiaterogenim dejstvom. Tokom razvoja, pre svega, centralnog tipa gojaznosti dolazi do poremećaja u sekretornom profilu masnog tkiva, nastaje pad serumske koncentracije ADN i dolazi do razvoja mnogobrojnih kardiometaboličkih poremećaja. Cilj rada je ispitivanje značaja određivanja serumskog ADN u proceni kardiometaboličkog profila i utvrđivanje povezanosti njegovog nivoa sa procenjenim desetogodišnjim rizikom za razvoj T2DM kod gojaznih osoba. Studija preseka sprovedena na Klinici za endokrinologiju, dijabetes i bolesti metabolizma, Kliničkog centra Vojvodine je obuhvatila 65 ispitanika sa hiperalimentacionim tipom gojaznosti. Kod ispitanika je procenjen desetogodišnji rizik za razvoj T2DM i sprovedena su odgovarajuća antropometrijska, laboratorijska i morfološka ispitivanja. Ispitanici sa sniženim serumskim ADN su imali nepovoljniji kardiometabolički profil u odnosu na ispitanike sa normalnom vrednošću serumskog ADN dok nije bilo razlike u nivou desetogodišnjeg rizika za razvoj T2DM između navedenih grupa. Takođe, ispitanici sa metaboličkim sindromom (MS) i ispitanici sa nealkoholnom masnom bolešću jetre (NAFLD) su imali niži serumski ADN u odnosu na osobe bez MS i osobe bez NAFLD. Kod gojaznih osoba postoji značajna povezanost serumskog ADN sa većim brojem pokazatelja kardometaboličkog profila ali ne i sa procenjenim desetogodišnjim rizikom za razvoj T2DM.</p> / <p>Obesity is often defined as the significant increase in proportion of fat mass in total body mass. Nowadays, obesity exhibits pandemic proportions and acquires character of the global health and social problem, as it represents the risk factor for the development of non-communicable diseases, especially type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Adipokines are molecules secreted by adipose tissue which play an important role in the regulation of various processes in the human organism. Adiponectin (ADN) is an adipokine with anti-diabetic, anti-inflammatory and anti-atherogenic effects. During development of, above all, central obesity, disorders in the secretory profile of adipose tissue are arising, decline in serum concentrations of ADN advents, which leads to occurrence of numerous cardiometabolic disorders. The aim of study is to examine the significance of determining serum ADN in assessing the cardiometabolic profile, and determining its association with the estimated ten-year risk of developing T2DM in obese persons. Cross-sectional study conducted at the Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, included 65 persons with hyperalimentation type of obesity. Ten-year risk of developing T2DM was assessed and appropriate anthropometric, laboratory and morphological evaluations were performed. Persons with lower serum ADN had worse cardiometabolic profile compared to those with normal serum ADN value, while there was no difference in the level of ten-year risk of developing T2DM between two groups. Also, subjects with metabolic syndrome (MS) and subjects with nonalcoholic fatty liver disease (NAFLD) had lower serum ADN compared to persons without MS and to those without NAFLD. There is a significant association of serum ADN with a larger number of cardiometabolic profile indicators but not with the estimated ten-year risk of developing T2DM.</p>
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Funkcionalni magnetno rezonantni imidžing u dijagnostici dijabetesne nefropatije kod bolesnika sa tipom 2 dijabetes melitusa / Functional magnetic resonance imaging in the diagnosis of diabetic nephropathy in patients with type 2 diabetes mellitusMrđanin Tijana 06 June 2019 (has links)
<p>Uvod: Dijabetes melitus (DM) je oboljenje koje poprima karakteristike globalne epidemije. Sve ţešše oboljevaju pacijenti mlaŤeg ţivotnog doba. Simptomi DM tip 2 su blagi, ţesto neprimetni, te se oboljenje otkriva kada se veš manifestuju komplikacije. Dijabetesna nefropatija (DN) je jedna od mnogobrojnih komplikacija dijabetes melitusa tip 2, koja se završava terminalnom bubreţnom insuficijencijom. DN se ţesto neblagovremeno dijagnostikuje, zbog ţega se kasno zapoţinje leţenje. Rano otkrivanje DN od kljuţnog je znaţaja, jer omogušava primenu terapijskih postupaka usmerenih na oţuvanje preostalih zdravih nefrona i prevenciju terminalne bubreţne slabosti. Cilj: Prikazati poremešaj difuzije molekula vode unutar bubrega kod DN, koriššenjem mapa prividnog koeficijenta difuzije, kvantifikacijom vrednosti prividnog koeficijenta difuzije (ADC) i frakcione anizotropije (FA). Materijal i metode: U prospektivnu studiju bilo je ukljuţeno 10 zdravih dobrovoljaca i 91 pacijent oboleo od DM tip 2. Pacijenti oboleli od DM tip 2 podeljeni su u ţetiri grupe na osnovu vrednosti procenjene jaţine glomerularne filtracije (JGF) (grupe: I JGF ≥ 90, II 89-60, III 59-30, IV ≤ 29 ml/min/1,73m²). Svim ispitanicima uraŤen je MR pregled bubrega, uz primenu DWI (b=0 i b=400 s/mm²) i DTI (b=1000 s/mm²) sekvence, na aparatu jaţine 1.5T. ADC i FA vrednosti raţunate su u šest regija od interasa, po tri u korteksu i meduli svakog bubrega. Dobijene vrednosti komparirane su sa laboratorijskim parametrima bubreţne funkcije (urea, kreatinin, mokrašna kiselina) i procenjenom JGF. Rezultati: Ne postoje statistiţki znaţajne razlike ADC i FA vrednosti parenhima, korteksa i medule levog i desnog bubrega kod zdravih dobrovoljaca i DM pacijenata. Kod DM pacijenata ADC je veša u korteksu nego u meduli (p=0,00), a FA vrednost je veša u meduli nego u korteksu (p=0,284). Urea, kreatinin i cistatin C imaju negativnu korelaciju sa ADC korteksa, medule i parenhima (p<0,05), a JGF ima pozitivnu korelaciju sa ADC korteksa, medule i parenhima, kao i sa FA medule (p<0,05) kod DM pacijenata. Na osnovu Post hoc testa za ADC, kod DM pacijenata postoje razlike izmeŤu I i IV grupe, izmeŤu II i IV grupe i III i IV grupe (p≤0,05). IzmeŤu godina ţivota, teţine, BMI, JGF, HbA1c, uree i ŠUK-a, postoji razlika DM pacijenata i zdravih dobrovoljaca (p<0,05). Niţa je vrednost FA medule DM pacijenata u odnosu na zdrave dobrovoljce (p<0,05). Postoji razlika ADC korteksa, medule i parenhima izmeŤu zdravih dobrovoljaca i DM pacijenata IV grupe, kao izmeŤu DM pacijenata I i II grupe u odnosu na IV grupu. TakoŤe postoji razlika izmeŤu FA medule zdravih dobrovoljaca i DM pacijenata I i IV grupe (p<0,05). Regresiona analiza pokazala je uticaj kreatinina na ADC desnog bubrega i ADC oba bubrega, dok procenjena JGF i cistatin C imaju uticaj na ADC desnog i levog bubrega, ADC oba bubrega i FA levog bubrega (p<0,05). Traktografija je prikazala narušenu arhitektoniku kod pacijenata sa oštešenom bubreţnom funkcijom. Zakljuţak: Postoji korelacija laboratorijskih parametara bubreţne funkcije i procenjene JGF sa ADC i FA vrednostima bubrega, što ukazuje na ulogu funkcionalnog magnetno rezonantnog imidţinga u dijagnostici dijabetesne nefropatije. Neophodna su dalja istraţivanja koja še doprineti standardizaciji MR protokola i potvrdi znaţaja MR biomarkera u dijagnostici DN. Na osnovu naših rezultata vrednost FA medule osetljiviji je parametar od ADC vrednosti u otkrivanju ranog oštešenja bubrega u sklopu dijabetes melitusa.</p> / <p>Introduction: Diabetes mellitus (DM) is a disease that takes on the characteristics of a global epidemic. Patients of younger age are more and more commonly affected. Symptoms of type 2 DM are mild, often imperceptible, and therefore the disease is usually detected when complications are already manifested. Diabetic nephropathy (DN) is one of the many complications of type 2 diabetes mellitus that leads to terminal renal failure. Diagnosis of DN is often late, causing the delay of the treatmen. Early detection of DN is crucial because it allows the application of therapeutic procedures aimed at preserving the remaining healthy nephrons and preventing terminal renal failure. Objective: To investigate a diffusion of water molecule within a kidney in DN using apparent diffusion coefficient maps, by quantification of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in diabetic patients with DM type 2. Material and methods: The prospective study comprised 10 healthy volunteers and 91 DM type 2 patients. DM patients were divided into four groups based on the values of the estimated glomerular filtration (eGFR) (groups: I eGFR ≥ 90, II 89-60, III 59-30, IV ≤ 29 ml/min/1.73m²). All subjects were scanned by 1.5T MR using DWI (b=0 and b=400 s/mm²) and DTI (b=1000 s/mm²) sequences. ADC and FA values were calculated in six regions of interest, three in cortex and three in medulla of each kidney. Obtaned values were compared to laboratory parameters of renal function (urea, creatinine, uric acid) and eGFR. Results: There were no statistically significant differences between ADC and FA values of parenchyma, cortex and medulla of the left and the right kidney in healthy volunteers and DM patients. In DM patients, the ADC value was higher in the cortex than in the medulla (p=0.00) and the FA value was higher in the medulla than in the cortex (p=0.284). The negative correlation was found between urea, creatinine and cystatin C with ADC cortex, medulla and parenchyma (p<0.05), and the eGFR was positively correlated with ADC cortex, medulla and parenchyma, and with FA medulla (p<0.05) in DM patients. Based on the Post hoc test for ADC, in DM patients there were differences between I and IV group, between II and IV group, III and IV group (p≤0,05). Regarding age, weight, BMI, GFR, HbA1c, urea, and glucose in the serum, there was a difference between DM patients and healthy volunteers (p<0.05). The FA of medulla in DM patients was lower than of healthy volunteers (p<0.05). There were differences in ADC of cortex, medulla, and parenchyma between healthy volunteers and DM patients of IV group, as well as between DM patients of I and II group compared to IV group. There were differences of medulla FA values between healthy volunteers and group I, accompanied by healthy and IV group of DM patients (p<0.05). Regression analysis showed the influence of creatinine on ADC of right kidney and ADC of both kidneys, while eGFR and cystatin C have an effect on ADC of right and left kidney, ADC of both kidneys and FA of left kidney (p<0.05). The tractography showed the disturbed architectonics in patients with impaired renal function. Conclusion: There is correlation of laboratory parameters of renal function and eGFR with ADC and FA values of the kidney, indicating the role of functional magnetic resonance imaging in the diagnosis of DN. Further research that will contribute to standardizing the MR protocol and confirming the importance of MRI biomarker in the diagnosis of DN are needed. Based on our results, the values of medulla FA is more sensitive parameter than the ADC value in detecting early kidney damage in the context of diabetes mellitus.</p>
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Uticaj metformina na nastanak deficita vitamina B12 kod pacijenata sa tipom 2 dijabetes melitusa / Effects of metformin induce vitamin B12 deficiency in type 2 Diabetes mellitusNikolić Stanislava 17 April 2019 (has links)
<p>Prema podacima iz 2011 godine, u Srbiji je približno 630 000 ljudi (8,6%) obolelo od dijabetes melitus-a, a procenjuje se da će taj broj porasti na 730 000 (10,2%) do 2030 godine. Preko 90% obolelih ima tip 2 dijabetes melitus (T2DM). Prva linija medikamentne terapije predstavljaju bigvanidi čiji je najznačajniji predstavnik metformin. Prema literaturnim podacima, u oko 10-30% sluĉajeva, kontinuirana upotreba metformina ima za posledicu smanjenu intestinalnu apsorpciju vitamina B12. Tačan patofiziološki mehanizam koji dovodi do metforminom indukovane malapsorpcije vitamina B12 nije u potpunosti ispitan i poznat i postoji nekoliko aktuelnih teorija s ciljem objašnjenja ovog kompleksnog problema. Cilj rada je bio utvrđivanje nivoa, dinamike, trenda i učestalosti promena vitamina B12, holotranskobalamina (B12 aktiv), homocisteina i folne kiseline tokom kontinuirane primene metformina tokom godinu dana. Studija praćenja je sprovedena u Centru za laboratorijsku medicinu a u saradnji sa Klinikom za endokrinologiju, dijabetes i bolesti metabolizma, Kliničkog centra Vojvodine. Ovom studijom je obuhvaćeno 50 ispitanika obolelih od T2DM a u momentu uvođenja metformina. Svim ispitanicima je određivana koncentracija vitamina B12, B12 aktiva, homocisteina i folne kiseline, u momentu uvođenja terapije kao i nakon 4, 8 i 12 meseci primene metformina. Za dvanaest meseci kontinuirane primene metformina, utvrđen je kontinuirani pad i redukcija vrednosti ukupnog vitamina B12 za 25.29 %, odnosno vrednosti B12 aktiva za 23.26 %. U toku ispitivanja, utvrđen je kontinuirani trend porasta vrednosti homocisteina u krvi, s statistički značajnim porastom vrednosti homocisteina nakon osam meseci primene metformina. Pošavši od predpostavki da metformin istovremeno blokira apsorpciju vitamina B12 u gastrointestinalnom traktu kao i raspoloživost iz postojećih, tkivnih rezervi, zatečene količine ovog vitamina u ciljnim ćelijama se postepeno redukuju i troše, rezultujući krajnjem snižavanju nivoa metabolički aktivnih oblika kobalamina, te posledičnoj akumulaciji homocisteina kako u ćelijskom, tako i u vanćelijskom prostoru. Na osnovu dobijenih rezultata ispitivanja može se predložiti opservacija nivoa ukupnog vitamina B12 i homocisteina u krvi pre uvođenja metformina u terapiju tipa 2 dijabetes melitusa kao i dvanaest meseci nakon toga. Na osnovu nivoa jednogodišnjeg pada koncentracija ukupnog vitamina B12, porasta koncentracija homocisteina, kao i drugih kliničkih i laboratorijskih parametara, može se razmatrati opcija uvođenja supstitucione terapije vitaminom B12 ili dalja opservacija nivoa vitamin B12 u krvi i ćelijskom prostoru.</p> / <p>According to data from 2011, in Serbia, approximately 630.000 people (8.6%) were diagnosed with diabetes mellitus, and it is estimated that this number will increase to 730.000 (10.2%) by 2030. Over 90% are type 2 diabetes mellitus (T2DM) patients. The first line of medication therapy is metformin. According to the literature data, in about 10-30% of cases, continuous use of metformin causes impared intestinal absorption of vitamin B12. The exact pathophysiological mechanism leading to metformin induced malabsorption of vitamin B12 has not been fully known, and there are several current theories to explain this complex problem. The aim of this study was to determine the level, dynamics, trend and frequency of changes in blood levels of total vitamin B12, holotranscobalamin (B12 active), homocysteine and folic acid during continuous application of metformin, over a year. The study was carried out at the Center of Laboratory Medicine in cooperation with the Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Vojvodina. This study included 50 T2DM patients at the time of the introduction of metformin therapy. Levels of vitamin B12, holotranscobalamin, homocysteine and folic acid are determined before and after 4, 8 and 12 months of metformin administration, to all subjects. After a year of metformin use, the level of total vitamin B12 has been reduced by 25.29%, as well as holotranskobalamin by 23.26%. During the study, a continuous elevation of homocysteine levels was determined, with statistically significant increase in homocysteine values after eight months of metformin administration. Starting from the assumption that metformin blocks the absorption of vitamin B12 in the gastrointestinal tract as well as the availability of existing tissue reserves, the amount of this vitamin in the target cells is gradually reduced, resulting in an extremely low level of metabolically active forms of this vitamin and the consequent accumulation of homocysteine in intracellular and extracellular space. On the basis of the obtained test results, it may suggest observation of the level of total vitamin B12 and homocysteine prior to the introduction of metformin in T2DM therapy and after one year thereafter. Based on the level of one-year decline of total vitamin B12 and the increase of homocysteine concentrations, as well as other clinical and laboratory parameters, substitution therapy with vitamin B12 or further monitoring of laboratory parameters of vitamin B12 metabolism may be proposed.</p>
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O SP1 (transcription factor Sp1) participa da regulação transcricional do Slc2a4 mediada pelo receptor de estrógeno ER-alfa em adipócitos 3T3-L1 / SP1 (transcription factor Sp1) participates in the transcriptional regulation of Slc2a4 mediated by estrogen receptor ER-alpha in 3T3-L1 adipocytesAndrade, João Nilton Barreto 15 May 2018 (has links)
O diabetes mellitus tipo 2 (DM2) é caracterizado pela presença de resistência à insulina, a qual pode ser modulada pelo estrógeno, tanto em fêmeas como em machos. Nesse processo, o transportador de glicose GLUT4 (gene Slc2a4, solute carrier family 2 member 4) desempenha papel importante, pois aumento da expressão do GLUT4 melhora o controle glicêmico. Estradiol (E2) regula a expressão do Slc2a4 por meio do balanço dos efeitos contrários de seus receptores (ERs): ER-alfa estimula e ER-beta inibe a expressão. Efeitos transcricionais dos ERs envolvem a participação de co-reguladores, destacadamente o SP1 (transcription factor Sp1), potente estimulador do Slc2a4. Entretanto, o papel do SP1 na regulação do Slc2a4 mediada pelos ERs é desconhecido; e este foi o objetivo do presente estudo. Investigou-se adipócitos maduros 3T3-L1, tratados por 24 horas com E2, agonista de ER-alfa (PPT) ou agonista de ER-beta (DPN). Avaliou-se: a expressão gênica (RT-qPCR) de Slc2a4 e Sp1; o conteúdo (Western blotting) total de GLUT4 e o nuclear de ER-alfa/beta e SP1; a atividade de ligação do SP1 no Slc2a4 (ensaio de mobilidade eletroforética); e a formação de complexos SP1/ER-alfa (imunoprecipitação). Os resultados confirmaram que E2 aumenta a expressão de Slc2a4/GLUT4 pela ação preponderante do ER-alfa. O agonista PPT aumentou: o conteúdo nuclear de SP1, a interação SP1/ER-alfa e a atividade de ligação do SP1 no Slc2a4. O agonista DPN indicou que a ação repressora do ER-beta não envolve o SP1. Conclui-se que o efeito estimulador do ER-alfa na expressão do Slc2a4 envolve mecanismo de transativação gênica via SP1. Essas observações colocam a cooperação ER-alfa/SP1 como um novo alvo para o desenvolvimento de medidas terapêuticas para resistência à insulina e diabetes mellitus tipo 2 / Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, which can be modulated by estrogen in both females and males. In this process, the glucose transporter GLUT4 (solute carrier family 2 member 4 gene - Slc2a4) plays an important role, since increasing GLUT4 expression improves glycemic control. Estradiol (E2) regulates the expression of Slc2a4, by a mechanism in which estrogen receptors (ERs) play opposite effects: ER-alpha stimulates, whereas ER-beta inhibits the expression. Transcriptional effects of ERs involve co-regulators, notably the transcription factor SP1, a powerful enhancer of Slc2a4. However, the role of SP1 in the ERs-mediated regulation of Slc2a4 is unknown; and that was the aim of the present study. Differentiated adipocytes 3T3-L1 were treated (24 hours) with E2, ER-alpha agonist (PPT) or ER-beta agonist (DPN). It was analyzed: gene expression (RT-qPCR) of Slc2a4 and Sp1; total content o GLUT4 and nuclear content of ER-alpha/beta and SP1 (Western blotting); binding activity of SP1 into Slc2a4 promoter (electrophoretic mobility shift assay); and content of nuclear SP1/ER-alpha complexes (immunoprecipitation). Results confirmed that E2 increases the expression of Slc2a4/GLUT4, by the dominant effect of ER-alpha. The ER-alpha agonist PPT increased the nuclear content of SP1, the interaction of SP1/ER-alpha, and the binding activity of SP1 into the Slc2a4. The agonist DPN evinced that ER-beta activity does not involve the SP1. In conclusion, the enhancer effect of ER-alpha upon Slc2a4 gene expression involves a transactivation mechanism via SP1. This observation point outs the cooperation of ER-alpha/SP1 as a new target for the development of approaches to treat insulin resistance and T2DM
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