Background: Diabetes is a common and costly disease that is expected to continue even to grow in prevalence and health expenditures over the coming decades. Type 2 diabetes is the most common diabetes type and is characterized by insulin resistance and relative insulin deficiency. Type 2 diabetes develops over a long period and is often undetected over years. During this time, people almost always first develop any of the pre-diabetic states, i.e. impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or a combination of both (IFG&IGT). This thesis focuses on type 2 diabetes only. In the following, the term diabetes is used to refer to type 2 diabetes only. Diabetes is associated with a sedentary lifestyle and obesity. While those are not the only factors contributing to the development and maintenance of diabetes, several studies have shown that prevention of diabetes among individuals at high risk through lifestyle change is possible, effective and cost-effective, especially targeting diet and exercise to reduce weight. No previous study had, however, estimated the cost-effectiveness of diabetes prevention strategies from a population-based perspective including healthy individuals and also considered IFG and IGT as two distinct pre-diabetic states. Objective: The overall objective of this thesis was to establish, describe and evaluate a model that can assess the cost-effectiveness of lifestyle intervention programs to prevent diabetes. Methods: First, a Markov Model was established using data from the literature. The cost of a German diabetes prevention program was estimated. Second, risk equations for change to worsened glucose states were estimated using factor analysis and logistic regression based on consecutive data from the Västerbotten Intervention Program (VIP). The risk equations described transition probabilities in the final model and were based on several risk factors such as age, sex, physical activity and smoking status. Third, information on the Short-Form 36 questionnaire from the VIP population was transformed into Short-Form 6D. Health utility weights (HUW) by glucose group and four risk factors were estimated using beta regression. Fourth, an updated Markov model was established using an updated model structure compared to the one in Paper I, program costs of Paper I, risk equations of Paper II, health utility weights of Paper III and updated cost and mortality estimates. Results: The first model in Paper I showed that lifestyle intervention programs have the potential to be cost-effective with a high degree of uncertainty. The risk equations in Paper II indicated that the impact of each risk factor depended on the starting and ending pre-diabetes state, where high levels of triglyceride, hypertension, and high body mass index were the strongest risk factors to transit to a worsened glucose state. The overall mean HUW in Paper III was 0.764 with healthy individuals having the highest HUW, those with diabetes the lowest and those in pre-diabetic states ranging in between. The intervention described in Paper IV was cost-effective for all sex and age scenarios ranging from 3,833 EUR/QALY gained (women, 30 years) to 9,215 EUR/QALY gained (men, 70 years). The probability that the intervention is cost-effective was high (85.0-91.1%). Conclusion: We established a model that can estimate the cost-effectiveness of different scenarios of initiatives to prevent diabetes. The prevention or the delay of the onset of diabetes is feasible and cost-effective. A small investment in a healthy lifestyle with the change in physical activity and diet together with weight loss can have a decent, cost-effective result. The full range of possibilities this model offers has not been evaluated so far. We have, however, shown that implementing a lifestyle intervention program like the Västerbotten Intervention Programme would be cost-effective.

As doenças cardiovasculares e o diabete melito fazem parte das DCNT prioritárias da OMS, devido às altas taxas de morbimortalidade e incapacidade que geram a cada ano. Estima-se que no mundo existam 387 milhões de diabéticos e outros 316 milhões de pessoas com características de risco, como pré-diabete. Cerca de 60% dos pacientes com DM2 desenvolvem doença cardiovascular, a qual inicia de forma concomitante aos distúrbios do metabolismo da glicose, podendo existir mecanismos fisiopatológicos comuns entre as doenças. Metade dos eventos coronarianos, inclusive a morte súbita, ocorrem em indivíduos assintomáticos, evidenciando a necessidade de novos marcadores precoces, já que em muitos deles a morte é a primeira manifestação. Recentemente, tem sido sugerido que os miRNAs envolvidos na regulação da expressão gênica podem ser caracterizados como biomarcadores em diversas doenças. Nosso objetivo é identificar alterações no perfil de miRNAs circulantes em indivíduos euglicêmicos e pré-diabéticos com e sem aterosclerose subclínica, utilizando a tecnologia de qPCR Arrays, com a finalidade de identificar candidatos a biomarcadores moleculares dessa condição. Encontrou-se que a aterosclerose subclínica esteve associada com o envelhecimento, a menopausa, etnia branca, dislipidemia, resistência à insulina, o aumento da adiposidade, leptina e do TNF-α. O aumento do miR98-5p e a diminuição dos miRNAs miR-212-3p, miR-145-5p, miR-93-5p, miR15a-5p, miR-19a-3p, miR32-5p levaram a ativação da via de sinalização da aterosclerose. Os resultados sugerem que a inflamação foi o principal mecanismo associado com o desenvolvimento de aterosclerose subclínica neste estudo. / Cardiovascular Disease and Diabetes Mellitus are relevant NCDs for the WHO. It´s estimated that, worldwide, there are 387 millions of diabetics and 316 millions of people with risk characteristics like prediabetes. About 60% of patients with T2DM develops cardiovascular disease, which starts at the same time as disorders of glucose metabolism, there may be common pathophysiological mechanisms among diseases. Half of coronary events, including sudden death, occurs in asymptomatic individuals. This fact, highlights the need for new early markers of the disease, especially in asymptomatic patients, since in many of them, death is the first manifestation. It has been recently suggested that miRNAs involved in pos-transcriptional regulation of gene expression, could be characterized as biomarkers of diseases. Our goal is to identify changes in the profile of circulating microRNAs in euglycemic and prediabetic patients with or without subclinical atherosclerosis, by quantitative Polymerase Chain Reaction array (qPCR Array) in order to find molecular biomarkers of this condition. We found that subclinical atherosclerosis was associated with aging, menopause, white ethnicity, dyslipidemia, insulin resistance, increased adiposity, leptin and TNF-α. The up-regulation of miR98-5p and the down-regulation miR-212-3p, miR-145-5p, miR-93-5p, miR15a-5p, miR-19a-3p, miR32-5p led to activation of the signaling pathway of atherosclerosis. The results suggest that inflammation was the main mechanism associated with the development of subclinical atherosclerosis in this study.

O trato gastrointestinal é um sítio de alta exposição antigênica, por isso requer a presença de mecanismos de regulação imunológica mediada por linfócitos T reguladores e T auxiliares produtores de IL-17 (Th17) na mucosa intestinal. Se houvera falha na indução desses mecanismos, pode ocorrer o desequilíbrio das populações de bactérias comensais da microbiota intestinal, denominado de disbiose, geralmente associado à ruptura da barreira intestinal e translocação de bactérias ou LPS para o sangue. Neste sentido, alguns estudos têm evidenciado a importância dos linfócitos Th17 no intestino, já que estas células tem a capacidade de manter a integridade da barreira intestinal e, como conseqüência controlar a colonização e translocação bacteriana. Em adição, em pacientes e animais diabéticos têm sido observada a correlação de altos níveis de LPS circulantes e resistência à insulina. Baseado nessas evidências, nosso objetivo foi avaliar o papel da citocina IL-17 no controle das alterações inflamatórias e metabólicas no modelo de diabetes do tipo 2 (DM2). Para isso, foram utilizados camundongos C57BL/6 selvagens (WT) ou deficientes do receptor da citocina IL-17 (IL-17R-/-) submetidos à dieta controle (DN), composta por 10% de gorduras, 70% de carboidratos e 20% de proteínas ou à dieta hiperlipídica (DH), composta por 60% de gorduras, 20% de carboidratos e 20% de proteínas. Nossos dados demonstraram que a deficiência do receptor de IL-17 protegeu os animais contra a obesidade, mas os mesmos desenvolveram maior hiperglicemia e hiperinsulinemia decorrente da resistência à insulina. Além disso, foi verificada a hiperplasia das ilhotas pancreáticas, anormalidades na arquitetura e intenso infiltrado inflamatório no intestino (íleo) dos animais IL-17R-/- comparados aos WT após DH. Esse fato parece estar correlacionado a um defeito da migração de neutrófilos para a mucosa intestinal, uma vez que foi detectada reduzida expressão gênica da quimiocina CXCL-1 e do receptor CXCR-2 no íleo desses animais. De maneira interessante, as populações de neutrófilos (CD11b+Ly6G+) e de macrófagos anti-inflamatórios (CD11b+CX3CR1+) mostraram-se aumentadas nos linfonodos mesentéricos dos animais IL-17R-/- após DH. Em seguida, foi constatada maior translocação bacteriana no sangue tanto de animais IL-17R-/- submetidos à DN como DH. Entretanto, a análise metagenômica do gene 16S revelou a prevalência de bactérias Bacteroidetes e Proteobacterias, principais representantes de bactérias gram-negativas, somente nas fezes dos animais IL-17R-/- submetidos à DH. Em conjunto, estes dados indicam que o eixo IL-17/IL-17R é importante na manutenção da homeostase intestinal e na regulação das alterações inflamatórias e metabólicas associadas ao DM2 / The gastrointestinal tract is a high antigenic exposure site, so it requires the presence of immune regulation mechanisms mediated by regulatory T lymphocytes and IL-17- producing T helper lymphocytes (Th17) in the intestinal mucosa. If there is a failure in the induction of these mechanisms, may occur the imbalance in the populations of commensal bacteria of the intestinal microbiota, called dysbiosis, generally associated with the break of the intestinal barrier and translocation of bacteria or their products like LPS into the blood. In this regard, some studies have evidenced the importance of Th17 lymphocytes in the intestine, since these cells have the ability to maintain the integrity of the intestinal barrier, and consequently controlling the colonization and bacterial translocation. In addition, in patients and diabetic animals have been observed correlation between high circulating levels of LPS and insulin resistance. Based on this evidence, our objective was to evaluate the role of IL-17 cytokine in the control of inflammatory and metabolic changes in the type 2 diabetes (T2DM). For this reason, were used C57BL/6 wild-type mice (WT) or lacking of IL-17 cytokine receptor (IL-17R-/-) mice undergoing to the control diet (ND) comprising 10% fat, 70% carbohydrate and 20% protein or high fat diet (DH), comprising 60% fat, 20% carbohydrates and 20% protein. These data demonstrate that IL-17 receptor deficiency protected the animals against obesity, but these mice developed hyperglycemia and hyperinsulinemia due to insulin resistance. Furthermore, we verified a hyperplasia of the pancreatic islets, abnormalities in architecture and intense inflammation in the intestine (ileum) of IL-17R-/- animals undergoing DH compared to WT. This appears to be correlated to a defect in the neutrophil migration to the intestinal mucosa, since was detected reduced gene expression of the CXCL-1 chemokine and CXCR-2 receptor in the ileum of these animals. Interestingly, the populations of neutrophils (CD11b+Ly6G+) and antiinflammatory macrophages (CD11b+CX3CR1+) were shown to be increased in the mesenteric lymph nodes of IL-17R-/- animals after DH. Later, it was found more bacterial translocation in blood, both in IL-17R-/- mice with ND or DH. However, the metagenomic analyzes of the 16S gene revealed increased of Proteobacteria and Bacteroidetes phyla, the main representatives of gram-negative bacteria, only in the faeces of IL-17R-/- mice underwent DH. Together, these data indicate that IL-17/IL-17R axis is important in maintaining intestinal homeostasis and the regulation of inflammatory and metabolic alterations associated to T2DM

INTRODUÇÃO: O diabetes melito tipo 2 constitui uma doença crônica, caracterizada pelo longo curso clínico, por não apresentar cura e por requerer, de forma variável, gerenciamento contínuo e permanente. Um aspecto que vem suscitando interesse é a qualidade de vida destes pacientes. OBJETIVO: Descrever o perfil e estudar as associações entre a Qualidade de Vida Relacionada à Saúde (QVRS) e variáveis sócio-demográficas e clínicas em idosos diabéticos tipo 2. MÉTODOS: Realizou-se um estudo epidemiológico transversal, em 117 idosos diabéticos tipo 2, atendidos no Ambulatório de Diabetes do Serviço de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. As variáveis independentes foram avaliadas por dois questionários: um sócio-demográfico e um clínico. A variável dependente, a QVRS, foi aferida pelo questionário \"Short Form General Health Survey\" (SF-36), constituído de oito dimensões. Para analisar os dados realizou-se uma análise bivariada e posteriormente, de regressão múltipla, por meio de modelos lineares generalizados, supondo distribuição de probabilidades gama com função de ligação logarítmica. RESULTADOS: O perfil da qualidade de vida deste grupo é inferior àqueles sem diabetes, comparando com dados da literatura; todas as dimensões do SF-36 apresentaram influência de pelo menos uma variável, no sentido de diminuição da qualidade de vida; o estado geral de saúde (EGS) foi a dimensão com maior associação (quatro variáveis); número de co-morbidades foi o fator negativo que se associou com maior número de dimensões do SF-36. CONCLUSÕES: Observou-se comprometimento da qualidade de vida tanto nas dimensões físicas como nas dimensões não físicas; A teoria que valoriza a sobrecarga (burden) do diabético como mecanismo importante na determinação da qualidade de vida é a que mais se adequou aos dados de nossa amostra. / INTRODUCTION: Type 2 Diabetes melito constitutes a chronic illness, characterized by the long clinical course, not presenting cure and requiring, in a changeable way, continuous and permanent management. An aspect that is generating interest is the quality of life of these elderly patients. OBJECTIVE: To describe the profile and to study the association between Health-Related Quality of Life (HRQL) and demographic and clinical variables of elderly people with type 2 diabetes. METHODS: It was realized an epidemiologic cross-sectional type study, with 117 elderly patients with type 2 diabetes, taken care in the Service of Endocrinologia and Metabologia, at Hospital das Clinicas (College of Medicine of the University of Sao Paulo). Service of Endocrinologia and Metabologia of the Hospital of the Clinics of the College of Medicine of the University of São Paulo. The independent variables were evaluated by two questionnaires: a demographic and a clinical. The dependent variable, the HRQL, was measured by the questionnaire \"Shorts General Form Health Survey\" (SF-36), wich considers eight domains. In order to analyze the data, it was realized a bivaried analysis and, after that, a multiple regression analysis, using generalized linear models, considering the distribution of probabilities to be gamma, with logarithmic function. RESULTS: The profile of the quality of life of the chosen elderly people wiht type 2 diabetes was worse than the quality of life of those people without diabetes, if compared with literature data; every dimension of the SF-36 indicated influence of at least one variable, towards the reduction of the quality of life; the general state of health (EGS) was the dimension with the greatest association (with four variables); the number of comorbidities was the negative factor that was associated with the greatest quantity of dimensions of the SF-36. CONCLUSIONS: It was observed a negative effect in the quality of life of those elderly people with type 2 diabetes in the physical domains as well as in the non-physical domains. The theory that values the overload of people with diabetes as an important tool in the determination of the quality of life is the one that is more suitable to the data of our sample.

O diabetes mellitus tipo 2 (DM2), uma doença que afeta milhões de pessoas em todo o mundo, é marcado pela presença de complicações micro e macrovasculares, as quais estão associadas à disfunção endotelial, inflamação e fibrose. A aldosterona, cujos níveis plasmáticos estão elevados em pacientes e modelos experimentais de DM2, aumenta a geração de espécies reativas de oxigênio (ERO) e a expressão de marcadores inflamatórios. As citocinas IL-1? e IL-18 são liberadas principalmente após ativação de plataformas moleculares denominadas inflamassomas, as quais incluem os receptores NLRP3. Recentemente, demonstramos que o receptor NLRP3 contribui para a disfunção vascular induzida pela aldosterona. Considerando a existência de evidências que a aldosterona, via receptor mineralocorticoide (MR) e NLRP3, induz a produção de mediadores inflamatórios e, consequentemente, ativação do inflamassoma, podendo assim contribuir para o processo inflamatório no diabetes, nós hipotetizamos que o bloqueio de receptores MR e NLRP3 previne a ativação do inflamassoma e reduz o desenvolvimento das alterações vasculares funcionais associadas ao DM2. Observamos que artérias mesentéricas de animais diabéticos apresentam aumento da expressão/ativação de caspase-1 e IL-11?, aumento dos níveis plasmáticos de IL-1?, aumento da atividade da caspase- 1 em macrófagos do lavado peritoneal e prejuízo no relaxamento dependente de endotélio, comparativamente a artérias do grupo controle. Os tratamentos com espironolactona (antagonista MR) e MCC950 (inibidor de receptor NLRP3) atenuam a disfunção vascular, reduzem a expressão e a atividade da caspase-1 e diminuem os níveis plasmáticos de IL-1?. Células de músculo liso vascular e macrófagos derivados da medula estimulados com aldosterona também apresentam aumento da expressão dos componentes do inflamassoma, o que poderia contribuir para as alterações observadas em animais diabéticos. Pacientes com DM2 apresentam correlação positiva entre os níveis de aldosterona e de IL-1? e/ou glicemia. Em conclusão, nosso estudo demonstra que a aldosterona induz disfunção vascular e processo inflamatório no diabetes tipo 2 através da ativação de MR e do inflamassoma NLRP3. / Type 2 diabetes mellitus (T2DM), a disease that affects millions of people around the world, is marked by the presence of micro and macrovascular complications, which are associated with endothelial dysfunction, inflammation and fibrosis. Aldosterone excess aggravates endothelial dysfunction in diabetes by promoting insulin resistance, fibrosis, oxidative stress and inflammation. Aldosterone activates the molecular platform inflammasome in cells of the immune system, an event that contributes to vascular dysfunction induced by the mineralocorticoid hormone. However, it is unclear whether activation of the inflammasome contributes to the effects of aldosterone in diabetes-associated vascular abnormalities. In the present study we tested the hypothesis that aldosterone induces vascular dysfunction in T2DM via activation of mineralocorticoid receptors (MR) and assembly of the NLRP3 inflammasome. To determine whether aldosterone activates the NLRP3 inflammasome and NLRP3 activation contributes to diabetes-associated vascular dysfunction, mesenteric arteries from control mice (db/m) and mice with type 2 diabetes (db/db), treated with vehicle, spironolactone (MR antagonist) or the NLRP3 antagonist MCC950, were used. Db/db mice exhibited increased vascular expression/activation of caspase-1 and IL-1?, increased plasma IL-1? levels, increased number of caspase-1-positive macrophages in the peritoneal lavage as well as reduced acetylcholine (ACh) vasodilation, compared to control db/m mice. Treatment of db/db mice with spironolactone and MCC950 reduced vascular caspase-1, decreased plasma IL-1? levels and partly restored ACh responses. Spironolactone treatment also reduced the number of caspase-1-positive-macrophages in db/db mice. Vascular smooth muscle cells and bone marrow-derived macrophages stimulated with aldosterone also exhibited increased expression of inflammatory components, which may contribute to diabetes-associated vascular changes. Patients with T2DM exhibited a correlation between aldosterone and IL-1? levels and/or glycemia. In conclusion, our study demonstrates that aldosterone induces vascular dysfunction and inflammatory process in type 2 diabetes through MR receptor activation and NLRP3 inflammation.

Trata-se de uma pesquisa quase experimental que objetivou avaliar as contribuições de um programa educativo, focado na automonitorização da glicemia capilar, para as pessoas com diabetes mellitus tipo 2, desenvolvida em unidade ambulatorial de um hospital de nível terciário do interior paulista, em amostra de 25 pessoas com diabetes mellitus tipo 2. O programa educativo teve duração de 12 meses, estruturado com cinco encontros, dos quais dois foram individuais e utilizados para realizar a coleta de dados, nos dois tempos do estudo, que ocorreram antes e após o programa educativo, respectivamente, e três na modalidade grupal, nos quais foram desenvolvidas as intervenções educativas por meio de ferramentas visuais e interativas, com ênfase no conceito de autoeficácia da Teoria Social Cognitiva. Todos os participantes receberam sete reforços educativos por contato telefônico, sobre os temas discutidos nos grupos. Compuseram o estudo as variáveis sociodemográficas, clínicas, antropométricas, exames laboratoriais, automonitorização da glicemia capilar, autocuidado, conhecimento sobre a doença e autoeficácia. Os dados de caracterização da amostra foram apresentados por meio da estatística descritiva, e as análises entre os tempos, antes e após a participação do programa educativo, foram realizadas por meio dos testes de Wilcoxon e McNemar, com o nível de significância estatística 5%. Na caracterização da amostra, houve predomínio do sexo masculino 14 (56,0%), adultos idosos com média de 60,16 (DP=8,58) anos de idade, tempo médio de diagnóstico de 17,28 (DP=8,22) anos. O exame laboratorial referente à glicemia de jejum aumentou no T12, e a hemoglobina glicada manteve o mesmo valor médio, após o programa educativo. Na automonitorização da glicemia capilar, houve resultados indicativos de melhora dos parâmetros, após a participação no programa educativo, para os itens referentes ao conhecimento do valor da glicemia pós-prandial (p=0,0039), interpretação dos resultados de glicemia capilar com as refeições e medicamentos (p=0,0156) e reconhecimento de \"fraqueza\" como um sintoma da hiperglicemia (p=0,0386). A variável de autocuidado com a doença apresentou resultado negativo no item sobre a prática de exercício físico específico, ao diminuir o valor médio após o programa educativo (p=0,0445). O escore médio de conhecimento sobre a doença aumentou após o programa educativo (p>0,05). Para a autoeficácia, a média total da escala diminuiu após o programa educativo, no T0 a média foi de 1,67 (DP=0,72) e no T12 1,55 (DP=0,51). O programa educativo contribuiu, de maneira positiva, para as variáveis da automonitorização da glicemia capilar, autocuidado com o diabetes mellitus e conhecimento sobre a doença. Observou-se aumento no valor do escore médio em seis itens da autoeficácia no T12. Os resultados mostraram contribuições positivas para as pessoas na realização da automonitorização da glicemia capilar, como forma de manter o controle da doença / This is a quasi-experimental study that aimed to evaluate the contributions of an educational program focused on the self-monitoring of capillary glycemia for people with type 2 diabetes mellitus developed in an outpatient unit of a tertiary-level hospital in the interior of São Paulo in a sample of 25 people with type 2 diabetes mellitus. The educational program lasted 12 months, structured with five meetings. Of the five meetings, two were individual and used to collect data, in the two study times, which occurred before and after the educational program, respectively; and three meetings in the group modality, in which the educational interventions were developed by means of visual and interactive tools, with emphasis on the concept of self-efficacy of Social Cognitive Theory. All the participants received seven educational reinforcements by telephonic contact, about topics discussed in the groups. The study was composed these variables: of sociodemographic, clinical, anthropometrics, laboratory tests, selfmonitoring of capillary glycemia, self-care, knowledge about the disease and selfefficacy. The characterization data of the sample were presented by means of descriptive statistics and the analyzes between the times before and after the participation of the educational program were held by means of the tests of Wilcoxon and McNemar, with the level of statistical significance 5%. In the characterization of the sample, there was a predominance of male 14 (56.0%), elderly adults with average of 60.16 (SD = 8.58) years old, average diagnosis time of 17,28 (SD = 8.22) years. The laboratory test for fasting glycemia increased in T12 and glycated hemoglobin maintained the same average value after the educational program. In the selfmonitoring of capillary glycemia, there were indicative results of improvement of the parameters, after participation in the educational program, for the items related to knowledge of the value of postprandial blood glucose (p = 0.0039), interpretation of capillary glycemia results with meals and medications (p = 0.0156), and recognition of \"weakness\" as a symptom of hyperglycemia (p = 0.0386). The self-care variable with the disease presented a negative result in the item on the practice of specific physical exercise, decreasing the average value after the educational program decreased (p = 0.0445). The average score of knowledge about the disease increased after the educational program (p> 0.05). For self-efficacy, the total average of the scale decreased after the educational program, at T0 the average was 1.67 (SD = 0.72) and at T12 1.55 (SD = 0.51). The educational program contributed positively to the variables of self-monitoring of capillary glycemia, self-care with diabetes mellitus and knowledge about the disease. There was an increase in the value of the average score in six items of self-efficacy in T12. The results showed positive contributions to people in the selfmonitoring of capillary glycemia as a way to maintain control of the disease

O principal distúrbio metabólico decorrente do Diabetes mellitus tipo 2 e da Síndrome Metabólica corresponde a alterações no metabolismo lipídico. Portanto, torna-se importante a melhor compreensão de alguns aspectos do metabolismo de lipoproteínas plasmáticas. Nesse sentido, a avaliação do metabolismo dos quilomícrons e da transferência de lípides de lipoproteínas plasmáticas para a lipoproteína de alta densidade (HDL), pode fornecer informações importantes relacionadas com o processo aterogênico. No presente estudo, foram estudados 15 indivíduos portadores de Diabetes mellitus tipo 2, 15 indivíduos com Síndrome Metabólica e 14 controles normolipidêmicos. Foi avaliada a cinética plasmática de uma nanoemulsão lipídica artificial com comportamento metabólico similar ao dos quilomícrons naturais, marcada com triglicérides (TG-3H) e éster de colesterol (EC-14C) radioativos. A nanoemulsão de quilomícrons artificiais foi injetada endovenosamente e amostras de sangue foram coletadas durante intervalos préestabelecidos. As curvas de decaimento plasmático dos lípides radioativos da nanoemulsão foram traçadas e as taxas fracionais de remoção (TFR) foram calculadas por análise compartimental. Para avaliação da transferência de lípides foi utilizada uma nanoemulsão semelhante a LDL (LDE) marcada com TG-3H e colesterol livre-14C (CL-14C) ou fosfolípides-14C (PL-14C) e EC-3H, como doadora de lípides para a HDL. Após incubação in vitro da LDE com o plasma, seguiu-se a precipitação das lipoproteínas que contem apolipoproteína B, restando no sobrenadante apenas a HDL. As taxas de transferência de lípides foram expressas em % de radioatividade encontrada no sobrenadante. Também foi determinado o diâmetro da HDL por espalhamento de luz. A TFR-EC dos grupos DM2 (p <0,05) e SM (p <0,01) comparado ao grupo controle apresentou-se diminuída, enquanto que as TFR-TG foram similares nos três grupos. Houve maior transferência de fosfolípides e colesterol nos grupos DM2 e SM comparando-se com grupo controle (p<0,001) A transferência de triglicérides e de éster de colesterol não diferiu entre os grupos. Não observou-se diferença no diâmetro da HDL nos três grupos. Concluindo, nossos resultados sugerem que a remoção plasmática dos remanescentes de quilomícrons encontra-se alterada em pacientes com SM e com DM2. Além disso, a transferência de lípides presentes na superfície das lipoproteínas para a HDL encontra-se aumentada nesses dois distúrbios metabólicos. Essas alterações podem contribuir com a maior incidência de aterosclerose nesses pacientes. / The main metabolic disturbances occurring as a result of type 2 diabetes mellitus (DM2) and Metabolic Syndrome (MetS) are alterations in the metabolism of lipids. It is therefore, important to better understand the aspects by which plasma lipoproteins are metabolized. The evaluation of chylomicron metabolism and lipid transfer of high density lipoprotein (HDL) can thus yield useful information regarding the atherosclerotic process. In this study, 15 Type 2 Diabetes individuals, 15 Metabolic Syndrome individuals and 14 normolipidemic control individuals were studied. The plasmatic kinetics of an artificial lipidic nanoemulsion mimicking the behavior of natural chylomicrons were evaluated. This artificial chylomicron nanoemulsion, labele with radioactive triglycerides (TG-3H) and radioactive cholesteryl oleate (CO-14C) was injected intravenously and blood samples collected at pre-established time intervals. The plasmatic decay curve of the radioactive lipids of the nanoemulsion was traced and the fractional clearance rate calculated (FCR) through compartmental analysis. In order to evaluate the lipid transfer, we used a nanoemulsion similar to LDL., labeled with TG-3H and free cholesterol -14C (CL-14C) or with phospholipids -14C (PL-14C) and CO-3H, as a lipid donator to HDL. After in vitro nanoemulsion incubation with the plasma, the lipoproteins containing apolipoprotein B were precipitated, resulting in a supernatant containing HDL. The lipid transfer rates were expressed in % of radioactivity measured in the supernatant. It was also determined the diameter of the HDL using light scattering technique. The TFR-EC for the DM2 (p <0.05) and MetS (p <0.01) groups when compared to the control group was reduced. The TFR-TG, on the other hand, remained similar in all three groups. The transfer of phospholipids and cholesterol for the DM2 (p<0.001) and MetS groups was greater than that of the control group (p<0.001). The triglycerides and ester cholesteryl transfer showed no differences between the studied groups. Furthermore, no difference in HDL diameter was observed in any of the three groups. In conclusion, our results suggest that the removal of chylomicron remnants from the plasma is altered in SM and DM2 patients. Furthermore, there is an increase in the transfer of lipids located on the surface of lipoproteins to HDL . These alterations may contribute to a higher incidence of atherosclerosis in these patients.

Patients’ perceptions of health care and support is a key determinant in self-efficacy and active participation in the management of chronic conditions. Nurses play a significant role in Diabetes Self-Management Education by providing clients with tools, empowerment and knowledge to self-manage their condition. The purpose of this study was to examine and describe diabetes patients’ perceptions of nurses’ support for self-management in Botswana. The aim was to improve clients’ skills in self-management and to strengthen diabetes health care management. This study was carried out at the Diabetes Clinic of Excellence, in the city of Francistown, the second largest city in Botswana. The study population comprised of Type 2 Diabetes patients registered at the Diabetes Clinic for their follow-up. All were aged 18 years and above. Three hundred and fifty-four (354) patients participated in the study. The study used a non-experimental, descriptive, quantitative design. Probability sampling method was used to recruit diabetes patients from the selected clinic. Data were were collected using a structured, researcher developed, questionnaire mostly in face-to-face interviews, a few participants completed the questionnaire. The Quantitative data analysis included descriptive and inferential statistics using SPSS (Statistical Package for Social Science Software (version 25). Spearman rho was used to determine statistical correlation between patients’ perceptions and their self-management practices. The findings showed that generally, patients’ perceptions of professional support was positive regarding most of the constructs measured. However, there were areas that showed less satisfaction with the support such as foot-care, risk control, and ability to identify signs of low and high blood sugar level and carrying of Identification Band (ID). Perceptions of nurses’ motivational behaviour showed varied responses. Patients’ self-care activities were sub-optimal and showed some variations which tended to correspond with their perceptions of professionals support. The Spearman's correlation results ranged from strong, moderate, and weak positive correlation. A few demographic variables showed some impact on self-care activities. Based on the findings, the study concludes that professional support through DSME and DSMS, self-management and patients’ perceptions of care play a significant role in diabetes management. / Health Studies / M.A. (Nursing Science)

A obesidade e o Diabetes mellitus tipo 2 se tornaram importantes problemas de saúde pública nos últimos anos. O aumento da prevalência do diabetes está intimamente relacionado ao aumento da prevalência da obesidade. As cirurgias bariátricas surgiram nos últimos cinqüenta anos e vêm se popularizando como uma opção terapêutica efetiva para a redução do peso e controle ou reversão do diabetes no paciente obeso. Dentre as técnicas cirúrgicas disponíveis, o Sleeve gástrico, que era utilizado como parte integrante da técnica de derivação bílio-pancreática ou como primeiro estágio, em pacientes de alto risco, a fim de prepará-los para a cirurgia definitiva, tem sido adotado, por alguns grupos de cirurgiões, como técnica definitiva. Como é recente sua utilização como procedimento bariátrico definitivo, faltam estudos que avaliem sua efetividade. O presente estudo teve por objetivo avaliar o Sleeve gástrico, para o controle ou reversão do Diabetes mellitus tipo 2, no paciente obeso. Para tanto, foi realizada uma revisão sistemática. A busca na literatura resultou em 698 títulos e resumos. Após aplicação dos critérios de inclusão foram recuperados 96 textos completos e incluídos, na revisão sistemática, sete artigos com ensaios clínicos controlados. Foi possível realizar metanálise entre estudos comparando o Sleeve gástrico à derivação gástrica com Y de Roux e com a bandagem gástrica. Foram avaliados os desfechos glicemia de jejum e hemoglobina glicosilada. O resultado da metanálise foi favorável ao Sleeve gástrico, em comparação ao Y de Roux, para o desfecho redução pós-operatória da hemoglobina glicosilada. O Sleeve gástrico se apresenta como mais uma opção terapêutica para a obesidade e correção das co-morbidades associadas. Porém, os resultados são bastante preliminares, e ensaios clínicos controlados, de boa qualidade metodológica, são necessários para melhor avaliação. / Obesity and type 2 diabetes mellitus have become lately important public health problems. The increase of diabetes is closely related to the increase of obesity. The bariatric surgeries appeared in the last fifty years, and have become popular as an effective therapeutic option for reducing weight and for controlling or even reverting diabetes in obese patients. Among the available surgery techniques the sleeve gastrectomy, which was used as an inner part of the bilio-pancreatic diversion technique or as first step in high risk patients in order to prepare them for the final surgery, has been used by some surgeons groups as a definitive technique. As its use as a definitive bariatric procedure is quite recent, there are still not enough studies to evaluate its effectiveness. The present study aims at evaluating the sleeve gastrectomy as a technique for the control or reversion of the type 2 diabetes mellitus in obese patients. Therefore, a systematic review was done. A research in the existing literature presented 698 titles and summaries. After applying the inclusion criteria, 96 complete texts were considered; seven papers with controlled clinic tests were included in the systematic review. This allowed to perform a metanalysis between studies, comparing the sleeve gastrectomy with the Roux-en-Y gastric bypass and with the adjustable gastric band. The comparison was based on the evaluation of the outcome of fast glycemia and glucosided hemoglobin. The result of the metanalysis was favorable to the sleeve gastrectomy, in comparison to the Roux-en-Y gastric bypass, for the closing of the post-surgery reduction of the glycoside hemoglobin. The sleeve gastrectomy thus appears as another therapeutic option towards obesity and correction of the related co-morbidities. But the results are still at an early stage, and so controlled clinical tests with high quality methodology are required in order to achieve a better evaluation.

Indivíduos obesos, portadores de diabetes mellitus tipo 2 (DM2), atingem controle glicêmico poucos dias após realização de derivação gástrica em Y de Roux (DGYR), antes mesmo de ocorrer perda de peso significativa. Entre os mecanismos propostos, para explicar o rápido controle glicêmico, a alteração da produção de hormônios gastrintestinais é muito estudada, porém pouco se explorou a expressão tecidual dos genes que os transcrevem. O presente estudo avaliou a resposta, em curto prazo, da expressão gástrica e intestinal de genes que transcrevem peptídeo semelhante ao glucagon 1 (GLP-1), peptídeo insulinotrópico dependente de glicose (GIP), peptídeo tirosina-tirosina (PYY) e grelina, e de níveis sistêmicos desses hormônios à DGYR, bem como, sua correlação com homeostase glicêmica pós-operatória. Mulheres obesas portadoras de DM2 (n=20) foram avaliadas antes e após 3 meses de DGYR. Todas as pacientes foram avaliadas em conjunto e, posteriormente, divididas em dois subgrupos de doentes, determinados pelo grau de remissão pós-operatória de DM2 (parcial ou completa) de acordo com o critério ADA. Biopsias do corpo e fundo gástrico, duodeno, jejuno e íleo foram coletadas por enteroscopia de duplo balão para análise de expressão dos genes GCG (precursor do GLP-1), GIP (precursor do GIP), PYY (precursor de PYY) e GHRL (precursor da grelina). As análises de expressão gênica foram feitas por abordagem global e alvo, por meio das técnicas de microarray e RT-qPCR, respectivamente. Concentrações plasmáticas dos hormônios transcritos pelos genes avaliados também foram dosadas em jejum e após teste de refeição mista, bem como níveis circulantes de peptídeo C, hemoglobina glicada (jejum), glicose, insulina e glucagon (jejum e após teste de refeição mista). Essa abordagem permitiu avaliar a correlação de dados teciduais de expressão gênica e de níveis circulantes de hormônios GI com marcadores sistêmicos de homeostase glicêmica. Após DGYR, alterações significativas na expressão de GCG, GIP, PYY e GHRL ocorreram ao longo dos segmentos GI estudados, em paralelo à melhora significativa de marcadores plasmáticos da homeostase glicêmica. Particularmente, aumento da expressão de GCG e diminuição da expressão de GIP ao longo do intestino foram acompanhados por alterações sistêmicas concordantes dos hormônios por eles transcritos. Essas alterações transcriptômicas se correlacionaram direta (GCG) e inversamente (GIP) com níveis de insulina e glicose, e, inversamente, com níveis de hemoglobina glicada (GCG e GIP). Apenas o hormônio GLP-1 se correlacionou inversamente com níveis de hemoglobina glicada. Além disso, as pacientes com remissão completa de DM2 apresentaram, em relação às medidas pré-operatórias, aumento de GCG no jejuno e íleo, e aumento significativo da área sob a curva de GLP-1 ativo após DGYR. No estômago excluso, ocorreu aumento da expressão de GHRL, mas os níveis sistêmicos de grelina não sofreram alterações significativas no pós-operatório. De acordo com nossos dados, DGYR modificou a expressão de genes que transcrevem hormônios GI capazes de influenciar a homeostase glicêmica. Essas alterações foram acompanhadas por modificações concordantes de níveis sistêmicos das incretinas GLP-1 e GIP e se correlacionaram com marcadores de melhora da homeostase glicêmica. Em conjunto, nossos resultados sugerem que DGYR pode influenciar a homeostase glicêmica por mecanismos que incluem modificação transcriptômica de genes relacionados a hormônios gastrintestinais / Obese subjects with type 2 diabetes mellitus (T2DM) achieve glycemic control few days after Roux-en-Y gastric bypass (RYGB), even before significant weight loss occurs. Among all proposed mechanisms to explain the rapid glycemic control after surgery, alteration of gastrointestinal (GI) hormones production is widely studied, however, GI expression of these genes is still little explored. The present study evaluated the short-term response of gastric and intestinal expression of genes transcribing glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), tyrosine-tyrosine peptide (PYY), and ghrelin and systemic levels of these hormones after RYGB, as well as their correlation with postoperative glycemic homeostasis. Obese women with T2DM (n = 20) were assessed before and after 3 months of RYGB. All patients were evaluated together and subsequently divided in two subgroups of patients, according the degree of postoperative T2DM remission (partial or complete), following ADA criteria. Biopsies of body and gastric fundus, duodenum, jejunum and ileum were collected by double-balloon enteroscopy for analysis of GCG (precursor of GLP-1), GIP (GIP precursor), PYY (precursor of PYY) and GHRL ghrelin precursor). Gene expression analysis was done by global and target approach, using microarray and RT-qPCR techniques, respectively. Plasmatic concentrations of hormones transcribed by the genes under study were also measured in fasted and after mixed meal test samples, as well as circulating levels of C peptide, glycated hemoglobin (fasting), glucose, insulin and glucagon (fasting and after mixed meal test). This approach allowed the correlation of tissue expression data and circulating levels of GI hormones with systemic markers of glycemic homeostasis. After RYGB, significant changes in GCG, GIP, PYY and GHRL expression were observed along the studied GI segments, in parallel with significant improvement in plasma markers of glycemic homeostasis. In particular, increased GCG expression and decreased GIP expression throughout the small intestine was followed by consistent systemic alterations of its related hormones. These transcriptomic changes are directly (GCG) and inversely (GIP) correlated with insulin and glucose levels and inversely with glycated hemoglobin levels (GCG and GIP). Only GLP-1 was inversely correlated with glycated hemoglobin levels. In addition, regarding the preoperative measurements, patients with complete T2DM remission presented increased GCG in jejunum and ileum, and significant increase in the area under curve of active GLP-1 after RYGB. In the excluded stomach, an increase in GHRL gene expression was recognized, but systemic levels of ghrelin did not changed significantly. According to our data, RYGB altered the expression of genes that transcribe GI hormones related to glycemic homeostasis. These changes were followed by expected modifications of GLP-1 and GIP incretin systemic levels and were correlated with improved glycemic homeostasis markers. Taken together, our results suggest that RYGB can influence glycemic homeostasis by mechanisms that include transcriptomic modification of genes related to gastrointestinal hormones