Orientadores: Antonio Carlos Boschero, Fernanda Ortis / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-24T09:44:17Z (GMT). No. of bitstreams: 1 Benedicto_KeliCristina_M.pdf: 3000980 bytes, checksum: 12e30944c74a94d0e816edbc8b474907 (MD5) Previous issue date: 2013 / Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital. / Note: The complete abstract is available with the full electronic digital thesis or dissertations. / Mestrado / Fisiologia / Mestra em Biologia Funcional e Molecular

Bakgrund: Diabetes mellitus typ 1 är en av de vanligaste kroniska sjukdomarna bland barn och ungdomar och de med diabetes mellitus typ 1 har en ökad risk att drabbas av ätstörningar. Skolsköterskan träffar dessa ungdomar inom skolan och deras uppgift är att arbeta hälsofrämjande och förebyggande samt ge stöd till eleven i det dagliga livet. Syfte: Var att belysa ätstörningar hos ungdomar med diabetes mellitus typ 1. Metod: En litteraturöversikt med en induktiv ansats. Resultat: Baserades på 20 vetenskapliga kvantitativa artiklar. Fem kategorier framkom; Risk- och skyddsfaktorer som påverkar ätstörningar, Levnadsvanors samband med ätstörningar, Skillnader och likheter mellan könen, Insulinmanipulation och Konsekvenser av ätstörningar. Slutsats: Denna litteraturöversikt visade att det fanns många faktorer som hade samband med ätstörningar hos ungdomar med diabetes typ 1. Koppling till skolsköterskans hälsofrämjande roll i diskussionen ger förslag på hur skolsköterskan kan arbeta hälsofrämjande gentemot ungdomar med diabetes typ 1 och ätstörningar. Det saknas kvalitativ forskning kring skolsköterskans hälsofrämjande arbete med ungdomar med diabetes typ 1 och ätstörning. Det vore därför intressant med forskning som visade på vilket stöd dessa ungdomar själv anser att de behöver för att hantera sin diabetes och ätstörning. / Background: Diabetes mellitus type 1 is one of the most common chronic diseases among children and adolescents, and those with diabetes mellitus type 1 have an increased risk of eating disorders. The school nurse meets these adolescents within the school and their purpose is to work with health promotion and prevention and to provide support to the student in daily life. Aim: To illustrate eating disorders in adolescents with diabetes mellitus type 1. Method: A literature review with an inductive approach. Findings: Based on 20 scientific quantitative articles. Five categories emerged; Risk and protective factors affecting eating disorders, Living habits associated with eating disorders, Gender differences and similarities, Insulin manipulation and Consequences of eating disorders. Conclusion: This literature review shows that there are many factors related to eating disorders in adolescents with type 1 diabetes. Link to the school nurse's health promotion role in the discussion provides suggestions on how the school nurse could work health promotion towards adolescents with diabetes type 1 and eating disorders. It would therefore be interesting with research that showed what support these young people themselves think they need to manage their diabetes and eating disorders. / <p>Godkännandedatum: 2019-11-04</p>

Bakgrund: I Sverige är det cirka 50 000 personer som lever med diabetes mellitus typ 1. Det är en kronisk komplex sjukdom som kräver livslång behandling.  Sampel med vården krävs under hela sjukdomsförloppet där en god vårdrelation blir betydande. Självkännedom och god självkänsla underlättar för egenvården eftersom det handlar om att kunna se de egna styrkorna för en god hanteringsförmåga av sjukdomen. Syfte: Syftet var att beskriva erfarenheter av egenvård hos unga vuxna med diabetes mellitus typ 1.  Metod: En kvalitativ litteraturöversikt med induktiv ansats har gjorts. Resultatet baseras på 12 vetenskapliga artiklar. Resultat:  Två huvudteman framkom i resultatet och ett av de var utmaningar med fyra underteman: rädsla och oro, begränsningar, övergång till vuxen livet och hur vardagen kan påverka egenvården. Andra huvudtemat var socialt stöd med tre underteman: stöd från familj och vänner, vårdpersonalens betydelse och okunskap från omgivningen påverkar egenvården. Slutsatser: Stöd från familj och vänner var av stor betydelse när det gällde hur de unga vuxna med diabetes mellitus typ 1 skötte egenvården. Vårdpersonal hade ett stort ansvar i att stötta och vägleda personer till egenvård. Utomståendes okunskap kunde leda till försämrad egenvård för personerna. / Background: In Sweden there are about 50 000 people living with diabetes mellitus type 1. It is a chronic complex disease and demands a lifelong treatment. Teamwork with the healthcare is required throughout the course of the disease and a good relationship with the health care providers becomes significant. Self-awareness and good self-esteem facilitate self-care when it comes to being able to see one’s own strengths for a good management ability of the disease. Aim: The aim was to describe experiences of self-care among young adults with diabetes mellitus type 1. Method: A qualitative literature research that has an inductive design has been done. The results are based on twelve different scientific articles. Results:  Two main themes have emerged in results and one of them was challenge with four sub themes: fear and anxiety, limitations, transitions to adult life and how daily life can affect self-care. The other main theme was social support with three sub themes: support from family and friends, the importance of healthcare professionals and lack of knowledge by others that affects self-care. Conclusion:  Social support from family and friends was important when it comes to how young adults with diabetes mellitus type 1 managed self-care. Healthcare professionals have a big responsibility in supporting and guiding people to self-care. Lack of knowledge from others could lead to mismanagement of self-care.

The increasing healthcare burden of type 1 diabetes (T1D) makes finding preventive or therapeutic strategies a global priority. This chronic disease is characterized by the autoimmune destruction of the insulin-producing β cells. This destruction leads to poorly controlled blood glucose and accompanying life threatening acute and chronic complications. The role of viral infections as initiating factors for T1D is probable, but contentious. Therefore, my goal is to better characterize the effects of viral infection on human β cells in their function of producing insulin and to define innate immune gene responses in β cells upon viral infection. These aspects were evaluated in various platforms including mice engrafted with primary human islets, cultured primary human islets, β cells derived from human stem cells, and a human β cell line. Furthermore, the contributions of cell-type specific innate immune responses are evaluated in flow cytometry-sorted primary human islet cells. Taken together, the results from these studies provide insights into the mechanisms of the loss of insulin production in β cells during virus infection, and characterize the antiviral innate immune responses that may contribute to the autoimmune destruction of these cells in T1D.

Little is known about what variables affect self-management practices of adolescents with T1D. Few studies have examined differences in self-management behaviors by stage of adolescence. Similarly, no studies have examined all of the attributes of self-management, including Collaboration with Parents and Goals. In order to fill the gaps in the literature, a secondary data analysis with a descriptive correlation design was conducted to describe T1D self-management behaviors (Collaboration with Parents, Diabetes Care Activities, Diabetes Problem Solving, Diabetes Communication and Goals) during early, middle and late stages of adolescence. This study also examined whether the roles of covariates (regimen, duration of illness (DOI), gender) in self-management behaviors vary by stage of adolescence. Data from 504 subjects aged 13 – 21 years were analyzed and the age variable was transformed into three adolescent stages early (13-14) (n=163), middle (15-16) (n=159) and late (17-21) (n=182). The findings revealed significant differences between adolescent stages on Collaboration with Parents and the Diabetes Problem Solving subscale. The covariate analysis showed no significant effect modification for the covariates and stage on any of the subscales so the results did not differ from the ANOVA model. Covariate analysis showed significant associations between regimen and Collaboration with Parents, Diabetes Care Activities and Diabetes Problem Solving. DOI showed significant associations only with Diabetes Problem solving and gender had significant associations with Diabetes Care Activities and Diabetes Communication. The mean scores on Collaboration with Parents show an incremental decline in collaboration with parents as adolescents move through stages. The higher mean Diabetes Problem Solving scores found in the late adolescent group compared correlated with a higher degree of problem solving in this group when compared to those in the early or middle adolescent stage group. Regimen had significant associations with three of the five subscales suggesting this is an important variable for future study. DOI did not have a significant impact on self-management whereas gender related differences in the areas of Diabetes Activities and Diabetes communication warrant further investigation.

Bakgrund: Diabetes Mellitus (DM) är en kronisk sjukdom som kan påverka flera kroppsliga funktioner, vilket i sin tur kan leda till svåra komplikationer. En av dessa är svårläkta sår, vilket är förknippat med en omfattande börda för patienterna. Syfte: Att beskriva patienters upplevelser av att leva med diabetiska fotsår vid DM typ 1 och 2. Metod: Studien genomfördes genom en litteraturöversikt med kvalitativ metod. Studien baserades på elva vetenskapliga artiklar som återfanns genom artikelsökning i databaserna CINAHL och MEDLINE samt manuell sökning. Artiklarna analyserades enligt analys av Friberg i fem steg. Resultat: Litteraturöversikten resulterade i fyra huvudteman; upplevelser av fysisk påverkan, upplevelser av ekonomisk påverkan, upplevelser av social påverkan och upplevelser av emotionell påverkan. Vidare sammanställdes nio subteman. Slutsats: Diabetiska fotsår hos personer med diabetes påverkar psykologiska och sociala aspekter, begränsar rörlighet och orsakar funktionsnedsättning. Brist på stöd leder till ensamhet och börda, medan smärta hindrar social interaktion. Sjuksköterskor kan med kunskap och gott bemötande bidra till ökad kunskap om egenvård och psykosociala effekter och främjar patientens självständighet, hälsa och välbefinnande. / Background: Diabetes Mellitus (DM) is a chronic disease that can affect several bodily functions, which in turn can lead to severe complications. One of these are hard-to-heal wounds, which is associated with an extensive burden for the patients. Aim: To describe patients’ experience of living with diabetic foot ulcers in DM type 1 and 2. Method: The study was conducted through a literature review using a qualitative method. The study was based on eleven scientific articles that were found through an article-search in the databases CINAHL and MEDLINE as well as through manual search. The articles were analyzed according to analysis by Friberg in five steps. Results: The literature review resulted in four main themes; experiences of physical impact, experiences of financial impact, experiences of social influence and experiences of emotional impact. Furthermore, nine subthemes were compiled. Conclusion: Diabetic foot ulcers in people with diabetes affect psychological and social aspects, limits mobility and cause disability. Lack of support leads to loneliness and a feeling of being a burden to others, while pain hinders social interaction. With knowledge and compassion, nurses can contribute to increase the patient’s knowledge about self-care and psychosocial effects which can promote the patient's independence, health, and well-being.

Bakgrund  Övergången från ung till vuxen med sin uppsjö av nya upplevelser ses ofta som en utmaning av många. Att få diagnosen diabetes mellitus typ 1 innebär en ny omställning och ett stort ansvarstagande för individen. Den unge vuxnes välbefinnande och hälsa beror till stor del på deras förmåga till egenvård. Sjuksköterskans kompetens samt undervisning- och handledningsförmåga är av stor betydelse för patienter som diagnostiseras med sjukdomen. Sjuksköterskor behöver därför ha förståelse för hur sjukdomen upplevs för att en god vägledning i den nya livsstilen ska kunna ges.  Syfte  Syftet med denna studie var att beskriva unga vuxnas upplevelser av egenvård vid diabetes mellitus typ 1.  Metod  En icke-systematisk litteraturöversikt genomfördes där 15 kvalitativa vetenskapliga artiklar inkluderades och låg till grund för resultatet. Med hjälp av olika sökkombinationer i databaserna PubMed och CINAHL kunde artiklarna inhämtas och kvalitetsgranskas utifrån Sophiahemmet Högskolas bedömningsunderlag. Därefter genomfördes en integrerad dataanalys av de valda resultatartiklarna och sorterades in i huvudkategorier och subkategorier.  Resultat  Tre huvudkategorier och nio subkategorier identifierade. Huvudkategorierna var: Känslomässiga upplevelser hos unga vuxna med diabetes, Utmaningar vid egenvården av diabetes och Stödet till egenvård vid diabetes. Resultatet visade på att rädsla och oro inför komplikationer som kan uppstå i vardagen var en gemensam känsla bland deltagarna, precis som känslan av trygghet från familj och vänner upplevdes som välbehövlig av samtliga.  Slutsats  Resultatet visade på gemensamma upplevelser kring utmaningar som de unga vuxna stöter på i sin vardag. Dessa upplevda utmaningar kan undvikas om omgivningen får rätt kunskap om sjukdomen och fortsätter stödja de unga vuxna i sin behandling. Ansvaret ligger huvudsakligen hos den unga vuxna, men med stöd från sjukvården samt familj och vänner stärks individens förmåga att klara av sin egenvård. / Background  The transition from juvenile to adult with its plethora of new experiences is often seen as a challenge by many. Receiving the life-long diabetes mellitus type 1 during this transitional phase, fundamentally changes an individual ́s everyday life and requires the individual to adapt to a new reality of self-care. A great deal of responsibility follows along being diagnosed with type 1 diabetes which means that guidance and support is in the nurses hands. The nurse's role in aiding the patient in their disease management is significant, hence the nurses need to have an understanding of how the disease is experienced in order to provide good guidance in the new lifestyle.  Aim  The aim of this study was to describe young adults' experiences of self-care in type 1 diabetes mellitus.  Method  A non-systematic literature review was conducted. Fifteen qualitative research articles were included. With the help of various search combinations from the databases PubMed and CHINAL, the articles were retrieved and quality reviewed based on Sophiahemmet Högskolas/University ́s assessment tools for classification and quality review. Thereafter an integrated data analysis was performed of the selected result articles and the data was sorted into main categories and subcategories.  Results  Three main categories and nine subcategories were identified. The main categories were: Emotional experiences of young adults with diabetes, Challenges in self-care of diabetes and Support for self-care in diabetes.  Conclusions  Common challenges that the young adults encountered in their everyday lives were shown in the results. These experienced challenges could be avoided if the surrounding people got the right knowledge about the disease and a continued support of the young adults with their self-management. With the support from healthcare providers, family and friends, the individual's ability to manage their own care will be strengthened.

Bakgrund:  Diabetes mellitus typ 1 är ett långvarigt hälsotillstånd som påverkar många människor världen över. Att leva med diabetes typ 1 innebär en rad utmaningar och krav, särskilt för unga vuxna som befinner sig i en period av snabb utveckling och förändringar.  Syfte: Beskriva unga vuxnas upplevelse av att leva med Diabetes mellitus typ 1.  Metod: Litteraturöversikt där resultatet baserades på elva vetenskapliga artiklar med kvalitativ ansats. Dataanalysen utfördes i enlighet med en tematisk analys av Braun och Clarke. Resultat: Resultatet presenterar hur unga vuxna upplever livet med Diabetes mellitus typ 1 utifrån två huvudteman ‘’Förhållningsätt’ till diabetes’ &amp; ‘’Stödets betydelse’’. Slutsats: Att leva med Diabetes mellitus typ 1 har en betydande inflytande på de unga vuxnas liv som skapar utmaningar och påverkar livskvalitén. Utöver andra stora livsförändringar så behöver dessa individer dessutom parera med att hantera en livslång sjukdom där olika relationer spelade en stor roll, samtidigt som känslor av utanförskap bekämpas. Fortsatt forskning krävs att uppnå en djupare förståelse och för att säkerställa tillämpning av god omvårdnad.

INTRODUÇÃO: A retinopatia diabética (RD) é uma das complicações mais frequentes dos diabetes mellitus tipo 1 (DM1). Durante a hiperglicemia, as células endoteliais da retina são expostas a altas concentrações de glicose e são incapazes de conter seu influxo. Isso resulta na ativação de vias deletérias intracelulares que culminam com o aumento de espécies reativas de oxigênio (ROS) e lesão neuronal e vascular. O estado pró inflamatório e pró trombótico ativa vias pró-oxidantes como a da NADPH oxidase. O excesso de ROS não é devidamente tamponado pelas vias antioxidantes (tais como as vias da glutationa e da tiorredoxina) em situações de hiperglicemia crônica, o que contribui para perpetuar o dano. OBJETIVO: Caracterizar uma população de pacientes DM1 quanto ao grau de RD e analisar a associação desta complicação microvascular com cinco polimorfismo de um único nucleotídeo (SNP) em genes pertencentes a vias pró- e antioxidantes. MÉTODOS: Pacientes acompanhados no ambulatório de diabetes de dois hospitais terciários do estado de São Paulo foram submetidos a fotos digitais do fundo de olho que incluíam os sete campos padronizados no estudo Early Treatment Diabetic Retinopathy Study (ETDRS) ou a uma oftalmoscopia binocular indireta; ambos foram avaliados por um único oftalmologista em cada um dos hospitais. A genotipagem dos SNPs foi feita por reação em cadeia de polimerase após transcrição reversa com duas sondas marcadas para cada reação. Os seguintes SNPs foram estudados: rs713041 (gene GPX4), rs17883901 (gene GCLC), rs6610650 (gene CYBB), -675 T/A (gene CYBA) e rs7211 (gene TXNIP). Os dados clínicos foram coletados por consulta ao prontuário médico ou questionário. Foi utilizado o modelo de regressão logística nominal politômica, tendo como categoria de referência a ausência de RD (ARD) ou dicotômica, tendo como categorias de referência a ausência de RD proliferativa (RDP) ou ARD. Após correção de Bonferroni, um valor de p <= 0,02 foi considerado significante. RESULTADOS: Um total de 341 pacientes (62% mulheres; idade média de 35 [±11] anos; com 22 [±9] anos de duração do DM1 e HbA1c de 8,6% [±1,6]) foi incluído. A prevalência de RDP foi de 30%, enquanto 42% dos pacientes apresentavam RD não proliferativa (RDNP). Somente os SNPs cuja distribuição dos genótipos respeitou o equilíbrio de Hardy-Weinberg foram analisados. Após ajuste para potenciais fatores de confusão, a presença do alelo T no SNP rs713041 (+718 C/T) no GPX4 foi inversamente associada à prevalência de RDP em pacientes do sexo feminino, com um odds ratio (OR) de 0,36 (intervalo de confiança [IC] de 95% de 0,17 a 0,75; p = 0,007) na análise dicotômica de RDP versus ausência de RDP. A presença do alelo T no SNP rs17883901 (-129 C/T) no GCLC conferiu risco para RDP na análise politômica (OR de 4,23; IC 95% de 1,38 a 12,93; p=0,01) e conferiu risco para a presença de qualquer grau de RD na análise dicotômica (ARD versus RDNP + RDP; OR de 3,07; IC 95% de 1,22 a 8,95; p=0,02). Não houve associação entre o SNP rs6610650 (gene CYBB) e RD nessa população. CONCLUSÃO: Os SNPs funcionais rs713041 no GPX4 e rs17883901 no GCLC modularam a susceptibilidade a RD na população de pacientes com DM1 estudada / INTRODUCTION: Diabetic retinopathy (DR) is one of the most frequent complications of type 1 diabetes mellitus (T1D). During hyperglycemia, retinal endothelial cells are exposed to high glucose concentrations and are unable to contain their influx. This results in the activation of deleterious intracellular pathways that culminate with the increase of reactive oxygen species (ROS) and neuronal and vascular injury. The pro-inflammatory and prothrombotic state activates pro-oxidant pathways such as NADPH oxidase. The excess of ROS is not adequately buffered by the antioxidant pathways (such as glutathione and thioredoxin pathways) in situations of chronic hyperglycemia, which contributes to perpetuate the damage. OBJECTIVE: To characterize a population of T1D patients regarding DR degree and to analyze the association of this microvascular complication with five single nucleotide polymorphisms (SNP) in genes belonging to pro- and antioxidant pathways. METHODS: Patients followed at the diabetes outpatient clinic of two tertiary hospitals in the state of São Paulo were submitted to digital photos of the eye fundus that included the seven fields standardized in the Early Treatment Diabetic Retinopathy Study (ETDRS) or to binocular indirect ophthalmoscopy; both were evaluated by a single ophthalmologist in each one of the hospitals. SNP genotyping was performed by polymerase chain reaction after reverse transcription with two labeled probes for each reaction. The following SNPs were studied: rs713041 (GPX4 gene), rs17883901 (GCLC gene), rs6610650 (CYBB gene), -675 T/A (CYBA gene) and rs7211 (TXNIP gene). The clinical data were collected by consulting the medical chart or by questionnaire. The polytomous nominal logistic regression model was used, having as reference category the absence of DR (ADR) or the dichotomous nominal logistic regression model was used, having as reference categories the absence of proliferative DR (PDR) or ADR. After Bonferroni correction, a p value <= 0.02 was considered significant. RESULTS: A total of 341 patients (62% female; mean age of 35 [± 11] years-old; diabetes duration of 22 [± 9] years and HbA1c of 8.6% [± 1.6]) was included. The prevalence of PDR was 30%, while 42% of the patients had non-proliferative DR (NPDR). Only SNPs whose distribution of genotypes respected the Hardy-Weinberg equilibrium were analyzed. After adjusting for potential confounding factors, the presence of the T allele at rs713041 (+718 C/T) in GPX4 was inversely associated with the prevalence of PDR in female patients, with an odds ratio (OR) of 0.36 (95% confidence interval [CI] 0.17-0.75; p = 0.007) in the dichotomous analysis of PDR versus absence of PDR. The presence of the T allele at rs17883901 (-129 C/T) in GCLC conferred risk for PDR in the polytomous analysis (OR of 4.23; 95% CI 1.38 to 12.93; p = 0.01) and for any degree of DR in the dichotomous analysis (ADR versus NPDR + PDR; OR of 3.07; 95% CI 1.22-8.95; p = 0.02). There was no association between the SNP rs6610650 (CYBB gene) and DR in this population. CONCLUSION: The functional SNPs rs713041 in GPX4 and rs17883901 in GCLC modulated the susceptibility to DR in the studied population of patients with T1D

O papel da hiperglicemia na patogênese das complicações crônicas do diabetes mellitus tipo 1 (DM1) está bem estabelecido; um dos mecanismos propostos para explicar seus efeitos deletérios é o aumento da formação dos produtos finais de glicação avançada (AGEs). Os AGEs alteram irreversivelmente a estrutura de macromoléculas, comprometendo sua função biológica. Além disso, a interação com receptores para AGE (RAGEs) favorece vias de transdução de sinal que culminam na geração de espécies reativas de oxigênio (EROs). Um segundo tipo de receptor de AGEs, o AGER1 contrapõe-se à toxicidade dos AGEs, graças ao estímulo à atividade antioxidante e à redução do estresse inflamatório. Uma enzima de potencial interesse é a sirtuína 1, uma desacetilase que desempenha importante papel na resposta ao estresse e a compostos tóxicos e que parece ter sua atividade diminuída no DM, sendo negativamente modulada pelos AGEs. O sistema tiorredoxina (TXN) é um dos principais sistemas antioxidantes endógenos; a TXN é capaz de interagir com várias proteínas, tal como a TXN interacting protein (TXNIP), implicada na patogênese do DM e de suas complicações. Há poucos estudos na literatura abordando a expressão de receptores de AGEs e sua associação com complicações crônicas microvasculares no DM1. Os objetivos deste trabalho foram avaliar a expressão do mRNA dos genes que codificam o RAGE (AGER), o AGER1 (DDOST), a sirtuína 1 (SIRT1) e a TXNIP (TXNIP) pela técnica de reação em cadeia da polimerase após transcrição reversa em tempo real (RT-qPCR) em células linfomononucleares de sangue periférico de portadores de DM1 com diferentes graus de comprometimento microvascular (retinopatia diabética [RD], neuropatia autonômica cardiovascular [NAC] e nefropatia diabética [ND]). Os resultados dos genes-alvo foram normalizados pela média da expressão de dois genes controles endógenos (beta 2 microglobulina e beta actina). A expressão dos genes-alvo também foi quantificada em uma população de indivíduos controles não diabéticos (n=26, 80% do sexo feminino, idade mediana de 30 anos). Um total de 150 portadores de DM1 foi classificado em dois grupos distintos: Grupo A: pacientes sem complicações crônicas microvasculares e/ou com RD não proliferativa leve (n=68; 61,7% do sexo feminino; idade de 33 anos; idade ao diagnóstico de 12 anos; duração do DM1 de 19 anos; HbA1c de 8,1%; dados expressos em mediana) e Grupo B: pacientes com pelo menos uma das complicações microvasculares (RD não proliferativa moderada/ grave ou RD proliferativa e/ou NAC e/ou ND; n=82; 66% do sexo feminino; idade de 33 anos; idade ao diagnóstico de 11 anos; duração do DM1 de 21 anos; HbA1c de 8,2%). Fumantes não foram incluídos no estudo. As diferenças entre os grupos foram analisadas por Teste de Mann-Whitney e as correlações entre as variáveis contínuas foram avaliadas pelo teste de Spearman. Comparando-se o grupo de portadores de DM1 com o grupo controle, observou-se uma diminuição na expressão de DDOST (p=0,01) e um aumento na expressão de TXNIP (p < 0,001) no grupo DM1. Nas análises da diferença de expressão por complicação microvascular, a expressão relativa de TXNIP foi maior nos grupos A e B versus o grupo controle (p=0,01 e p=0,04, respectivamente); nos pacientes com a presença de RD não proliferativa moderada/grave e proliferativa (n=44) e naqueles com ausência de RD ou com RD não proliferativa leve (n=86) (p=0,0012 e p=0,01, respectivamente) em relação ao grupo controle; nos pacientes sem NAC (n=104) e com NAC (n=46) (p=0,03 e p=0,04, respectivamente) versus o grupo controle e por fim, em relação à taxa de filtração glomerular (TFGe) estimada, tanto os pacientes com valores <60 mL/min como aqueles com valores < 60 ml/min apresentaram maior expressão de TXNIP em relação ao grupo controle (p=0,01 e p=0,005, respectivamente). Os pacientes com ND (n=44) também apresentaram menor expressão relativa do gene DDOST (p=0,031) quando comparados aos pacientes sem ND (normoalbuminúricos, n=107) e ao grupo controle (p=0,011); os pacientes com TFGe <60 mL/min também apresentaram menor expressão de DDOST em relação ao grupo controle (p=0,03) Observou-se ainda uma correlação positiva da expressão de SIRT1 com a do AGER (? Spearman=0,51; p < 0,0001) e do DDOST (? Spearman=0,51; p < 0,0001). A expresssão de TXN correlacionou-se positivamente com a expressão de TXNIP (? Spearman=0,65; p < 0,0001), de SIRT1 (? Spearman=0,41; p < 0,0001) e de DDOST (? Spearman=0,23; p 0,004). Em um subgrupo de 30 portadores de DM1, observou-se que aqueles que consomem uma dieta rica em AGE têm maior expressão relativa de AGER (RAGE) (p=0,03). A expressão aumentada de TXNIP nas células linfomononucleares é afetada pelas anormalidades metabólicas que cursam com o DM1, mas não refletem a presença das complicações microvasculares. Por outro lado, a expressão do gene que codifica o AGER1 parece refletir o acometimento renal, já que está diminuída nos pacientes com ND e naqueles com TFGe < 60 mL/min/1,73m2 / The role of hyperglycemia in the pathogenesis of chronic complications of type 1 diabetes (T1D) is well established; one of the mechanisms proposed to explain its deleterious effects is the increased formation of advanced glycation end products (AGEs). AGEs irreversibly alter macromolecule structure, compromising its biological function. In addition, AGEs interact with its specific receptor RAGE (encoded by AGER) leading to the generation of reactive oxygen species (ROS). The AGER1 receptor (encoded by DDOST) counteracts RAGE signaling by stimulating cellular antioxidants and reducing inflammatory stress. An enzyme of potential interest is sirtuin 1, a deacetylase that plays an important role in the response to stress and to toxic compounds that may have their activity decreased in diabetes, being negatively modulated by AGEs. The Thioredoxin (TXN) system is a major endogenous antioxidant system; TXN is able to interact with several proteins, such as TXN interacting protein (TXNIP), implicated in the pathogenesis of diabetes and its complications. There are few studies addressing the expression of AGEs receptor and its association with microvascular chronic complications in T1D. The objectives of this study were to evaluate mRNA expression of the genes encoding RAGE (AGER), AGER1 (DDOST), sirtuin 1 (SIRT1) and TXNIP (TXNIP) (quantitative RT-PCR with the use of TaqMan probes) in peripheral blood mononuclear cells (PBMC) of T1D patients with diferent degrees of microvascular complications (retinopathy [DR], cardiovascular autonomic neuropathy [CAN] and nephropathy [DN]). The results of the target genes were normalized by the mean expression of two housekeeping genes (beta 2-microglobulin and beta actin). A total of 130 patients with T1D was sorted into two groups: Group A: patients without microvascular chronic complications or presenting mild non-proliferative DR (n = 68; 61.7% female; age 33; age at diagnostic 12; DM1 duration of 19 years, HbA1c 8.1%, data expressed as median), and Group B: patients with at least one of microvascular complication (moderate/severe non-proliferative DR or proliferative DR or CAN or ND; n = 82; 66% female; age 33 years; age at diagnosis of 11 years; duration of T1D of 21 years, HbA1c 8.2%; data expressed as median). Smokers were excluded from the study. Differences between groups were analyzed by Mann-Whitney test and correlations between continuous variables were assessed using Spearman\'s test. T1D patients presented, respectively, higher and lower relative expression of TXNIP (p<0.001) and DDOST (p=0.01) in comparison to the control group. In the analyses considering diabetes complications, TXNIP expression was higher in Groups A and B (p=0.01 and p=0.04, respectively) versus the control group. Patients with proliferative or moderate/severe non-proliferative DR (n=44) and also patients with mild non-proliferative DR or without DR (n=86) presented higher TXNIP expression versus the control group (p=0.0012 and p=0.01, respectively). Patients without (n=104) and with (n=46) CAN presented higher TXNIP expression than the control group (p=0.03 and p=0.04, respectively); finally, concerning estimated glomerular filtration rate (eGFR), both the group of patients with values <60 mL/min and < 60 ml/min presented higher TXNIP expression versus the control group (p=0.01 and p=0.005, respectivamente). Patients presenting DN (n=44) had a lower DDOST expression in comparison to patients without DN (n=107) (p=0.031) and to the control group (p=0.011); patients with eGFR <60 mL/min also presented a lower expression of DDOST in comparison to the control group (p=0.03). A positive correlation was observed between expression of SIRT1 and AGER (? Spearman=0=51; p < 0.0001) and between expression of SIRT1 and DDOST (? Spearman=0,51; p < 0.0001). The expression of TXN positively correlated with the expression of TXNIP (p Spearman=0.65; p < 0.0001), SIRT1 (p Spearman=0.41; p < 0.0001) and DDOST (p Spearman=0.23; p 0.004). In a subgroup of 30 T1D patients, a higher expression of the gene encoding RAGE was observed in those patients consuming a diet enriched in AGEs (p=0.03). Expression of TXNIP in PBMC is affected by the metabolic abnormalities of T1D but does not reflect the presence of microvascular complications while expression of the gene encoding AGER1 seems to reflect diabetic kidney impairment since it is decreased in patients with DN and in patients with an eGFR < 60 mL/min/1.73m2