Contexte: Le diabète de type 2 est un problème de santé publique important. La pratique régulière de l’activité physique contribue à la prévention de cette maladie chronique. Toutefois, peu de recherches portent sur l’association entre l’activité physique de transport, notamment la marche utilitaire, et le diabète. Objectif : L’objectif de cette étude est d’examiner l’association entre la présence d’un diagnostic de diabète de type 2 et les pratiques de marche utilitaire dans un échantillon transversal. Méthode : Cette étude est une analyse secondaire de données provenant d’un projet de recherche sur l’implantation d’un système de vélos libre-service. 7012 adultes ont été recrutés par téléphone au printemps 2009, à l’automne 2009 et à l’automne 2010. La marche utilitaire a été mesurée en utilisant des questions adaptées du International Physical Activity Questionnaire (IPAQ). L’association entre la marche utilitaire et le diabète auto-rapporté a été examinée au moyen d’analyses de régression logistique multivariées. L’influence des variables socio- démographiques, du niveau d’activité physique autre et de l’indice de masse corporelle a été contrôlée. Des analyses de sensibilité ont aussi été faites, utilisant un seuil différent pour le temps de marche utilitaire. Résultats : Dans le modèle final, la marche utilitaire est associée à une prévalence du diabète plus faible (RC=0,721; IC 95% : 0,547-0,950). Conclusion: La pratique de la marche utilitaire est associée à une prévalence plus faible de diabète auto-rapporté. La promotion de ce type d’activité physique aurait sa place dans la prévention du diabète dans une perspective de santé publique. / Background: Type 2 diabetes is an important public health problem. Regular involvement in physical activity contributes to the prevention of this chronic disease. However, limited research has examined associations between transportation physical activity, especially utilitarian walking, and diabetes. Purpose: To examine the association between utilitarian walking and the prevalence of diabetes in a cross-sectional sample. Methods: Secondary analysis of data from a research project on the reach and potential impact of the implementation of a public bicycle share program was conducted. A sample of 7012 adults were recruited to telephone surveys in spring 2009, fall 2009, and fall 2010 via random-digit dialing with oversampling in locations where the public bike share was available. Utilitarian walking was estimated using questions adapted from the International Physical Activity Questionnaire (IPAQ). Multivariable logistic regression models examined the association between utilitarian walking and diabetes. The influence of socio- demographic covariates, involvement in other physical activities, and body mass index were controlled and sensitivity analyses were performed. Sensitivity analyses were performed using a different cut-off for utilitarian walking time. Results: In final models, utilitarian walking was associated with a lower likelihood of self-reporting diabetes (OR=0.721; 95% CI: 0.547, 0.950). Conclusion: Adoption of utilitarian walking is associated with a lower likelihood of reporting diabetes. Replication of these results in longitudinal studies could have implications for strategies to encourage people to incorporate more walking into their daily routine.

Le tissu adipeux blanc n'est pas un simple réservoir énergétique, il secrète également de nombreuses molécules appelées adipokines. En condition basale, les adipokines participent à l'homéostasie générale en permettant la régulation de diverses fonctions et voies métaboliques. Au cours du développement de l'obésité, la physiologie du tissu adipeux est fortement perturbée. Cela se traduit par des dysfonctionnements parmi lesquels l'établissement d'un état inflammatoire chronique à bas bruit. Ces perturbations au sein du tissu adipeux concourent à la dysrégulation de l'expression des adipokines, conduisant à un dysfonctionnement de certaines voies métaboliques, au niveau adipocytaire mais aussi au niveau systémique ce qui aboutit à un état d'insulino-résistance pouvant déboucher sur le développement d'un diabète de type 2. De nombreuses études épidémiologiques montrent qu'une carence en vitamine D est associée à diverses pathologies telles que certains cancers, certaines maladies auto-immunes ou maladies cardiovasculaires. Par ailleurs, il existe une corrélation inverse entre les taux plasmatiques de 25(OH)D et la prévalence de l'obésité, de l'hypertension artérielle, et du diabète de type 2. Cependant, le lien de causalité entre carence en vitamine D et obésité n'est à ce jour pas clairement démontré. Le but de cette thèse est donc de mieux comprendre le lien qui existe entre carence en vitamine D, obésité et désordres physiologiques associés. / White adipose tissue is not a simple energy reservoir, it also secretes several molecules called adipokines. In standard conditions, adipokines are involved in general homeostasis permitting the regulation of numerous functions and metabolic pathways. During the development of obesity, adipose tissue physiology is severely disrupted. This results in dysfunction such as low-grade inflammatory status. The accumulation of these disturbances within adipose tissue generates a dysregulation of adipokines secretion. This will have for consequences a failure of some metabolic pathways resulting in insulin-resistant state leading to type 2 diabetes. Several epidemiological studies show a link between vitamin D deficiency and numerous pathologies like cancers, immunity deseases or cardiovascular deseases. In addition, there is an inverse correlation between plasma levels of 25(OH)D and the prevalence of obesity, hypertension and type 2 diabetes. However, the link between vitamin D deficiency and obesity is not well established. The aim of this thesis is to better understand the link between vitamin D deficiency, obesity and physiological disorders associated. For this purpose, we have evaluated vitamin D effects on adipose tissue and adipocyte biology (inflammation, glucose uptake) and subsequently effects of vitamin D supplementation on diet-induced obesity. In a first study in vitro, we have showed an anti-inflammatory effect of vitamin D on adipocyte. This effect appears to be VDR-dependant and implies a modulation of NFκB signaling pathway. This study could partly explain le link between vitamine D deficiency and low-grade inflammation associated with obesity.

L'Approche Centrée Patient (ACP) permet sur le plan conceptuel la réalisation d'une démarche éducative vis-à-vis du patient diabétique de type 2. Mais la question de son fonctionnement se pose en pratique clinique de médecine générale. Dans le cadre d'une étude exploratoire qualitative phénoménologique, une Démarche Educative DEADIEM a été testée auprès de 10 patients diabétiques de type 2 inclus par 5 médecins généralistes pour en comprendre son fonctionnement. Cette démarche comprenait l'exploration de la perspective du patient, ce qui est VRAI (Vécu, Représentation, Attentes, Important) pour lui, une démarche explicative, des conseils hygiéno-diététiques adaptés et un objectif de compréhension commune avec le médecin avec évaluation à 3 mois de ses résultats. En confrontant les données du discours avec les modèles transthéorique et transactionnel par procédure de triangulation théorique, cette démarche a corroboré une dynamique d'adaptation « coping », des processus expérientiels et comportementaux favorisant ou pas des changements. Les médecins traitants ont été sollicités pour parler de leur perception de la relation. L'étude a illustré l'interaction symbolique qui existe entre des représentations « personnages » que chacun se fait de l'autre et qui peuvent bloquer ou faciliter la relation et la compréhension commune. Les médecins traitants ont pu exprimer de manière réaliste leurs limites et les difficultés de la relation transférentielle. A l'issu de cette étude, l'ACP, enrichi par d'autres modèles, est apparue comme un processus thérapeutique systémique qui peut être accessible à tout médecin généraliste, enseignable et faire l'objet de travaux de recherche complémentaires / The Patient Centered Approach (PCA) allows, on the conceptual level, to undertake an educative counseling program for type 2 diabetic patients. The question of its efficiency remains unclear in everyday general practice. In the setting of an exploratory phenomenological qualitative research DEADIEM, an experiential educative counseling based on a patient centered care model, was tested on a population of ten type 2 diabetic patients selected by five general practitioners to understand its functioning. This study investigated the patient’s perspective, their real experience, beliefs, expectations, references. An explanatory procedure and adapted hygieno-dietetic counseling was proposed together with an objective of common ground between patient and practitioner. The results were evaluated after three months. By triangulating data extracted from the patient’s transcript with other transtheoretical model and transactional models, the study revealed coping dynamic, experiential and behavioral processes which favoured or not changes. General practitioners were asked to express their perception of the physician patient relationship. The study illustrated the symbolic interaction existing between the “personal fronts” representations that anyone has about others that may block or facilitate relation and common understanding. GPs have been able to express in a realistic way their limits and the difficulties of transferential relationship. At the end of the study, PCA, enriched by other models appeared as a systemic therapeutic process that can be of ready access to any GP, can be taught and must be the subject of further research

Le diabète de type 2 résulte d’un déséquilibre entre les capacités de sécrétion de l’insuline par les cellules bêta-pancréatiques et son action au niveau de ses tissus cibles. Dans le prédiabète, l’hypersécrétion d’insuline compense l’insulino-résistance et cet état est généralement associé à l’obésité et à l’accumulation de tissu adipeux.L’objectif de ma thèse a été d’étudier la biocommunication entre le tissu adipeux viscéral et la cellule bêta-pancréatique lors du prédiabète et du diabète de type 2, en me focalisant sur deux médiateurs originaux, les isoprostanes et les miARNs. Nous avons observé une diminution de la sécrétion d’isoprostanes par le tissu adipeux péripancréatique au cours de l’obésité chez le rat Zucker fa/fa. Spécifiquement observé dans ce tissu adipeux ectopique, ce résultat s’explique par une induction des principales enzymes antioxydantes et une réduction de l’expression de la sPLA2 IIA chez les animaux obèses. Remarquablement, une des isoprostanes, la 15-F2t-Isoprostane ainsi que son épimère aux concentrations de 10 nM et 10 μM inhibent la sécrétion d’insuline gluco-stimulée dans les îlots pancréatiques isolés de rat Wistar. Cet effet pourrait s’expliquer par la liaison de cette isoprostane avec le récepteur au thromboxane A2, dont l’expression génétique et protéique a été mise en évidence pour la première fois dans les îlots de Langerhans et les cellules bêta. La réduction de l’inhibition de la sécrétion d’insuline chez le rat Zucker fa/fa, par une biocommunication paracrine, pourrait favoriser les mécanismes de compensation bêta-cellulaire. Par ailleurs, la production de miARNs, contenus dans des vésicules extracellulaires, par le tissu adipeux omental a été analysée chez l’homme par small RNAseq. Chez des patients obèses, la production de miARNs est modifiée lors de l’insulino-résistance et du diabète de type 2 avec des conséquences possibles sur la fonctionnalité des cellules bêta. Des miARNs différentiellement exprimés lors du diabète de type 2 pourraient ainsi participer à son apparition et représenter de nouveaux biomarqueurs et cibles thérapeutiques. Pour conclure, ces travaux de thèse ont permis de mettre en évidence de nouveaux mécanismes de biocommunication entre le tissu adipeux et les cellules bêta-pancréatiques. / Type 2 diabetes occurs as a result of an unability of pancreatic beta-cells to meet the insulin demand in its target tissues. During prediabetes insulin hypersecretion compensate for insulin resistance and this state is usually associated with obesity and excess body fat.The aim of my thesis was to study the biocommunication between visceral adipose tissue and pancreatic beta-cells during prediabetes and type 2 diabetes, with a focus on two original mediators, isoprostanes and miRNAs. We observed a decrease in isoprostane secretion by peripancreatic adipose tissue during obesity in Zucker fa/fa rats. In this ectopic adipose tissue, this observation may be related to an induction of some antioxidant enzymes and a reduction of the expression of sPLA2 IIA in obese animals. Remarkably, 15-F2t-Isoprostane as well as its epimer used at concentrations of 10 nM and 10 μM inhibited glucose-stimulated insulin secretion in isolated pancreatic islets. This effect could be explained by the binding of isoprostanes to the thromboxane A2 receptor, whose gene and protein expression has been demonstrated for the first time in islets and beta-cells. In Zucker fa/fa rats, less inhibition of insulin secretion through a paracrine biocommunication, could favor beta-cell compensatory mechanisms. Furthermore, the production of miRNAs, contained in extracellular vesicles released by omental adipose tissue, was analyzed in humans by small RNAseq. In obese patients, miRNAs production is altered during insulin resistance and type 2 diabetes with possible consequences for beta-cell function. Differentially expressed miRNAs in type 2 diabetes may participate in its development and represent novel biomarkers and therapeutic targets. In conclusion, this thesis highlighted new biocommunication mechanisms between adipose tissue and beta-pancreatic cells.

O diabetes melito tipo 2 é uma doença com alta prevalência e suas consequências vão além das doenças cardiovasculares. A fragilidade óssea foi recentemente incorporada à lista de suas complicações. Paradoxalmente, a massa óssea do DM2 é normal ou elevada quando comparada à da população normoglicêmica. Assim, torna-se necessário explorar outras ferramentas capazes de inferir parâmetros de qualidade óssea bem como de outros mecanismos que levam a fragilidade óssea no DM2. O objetivo do trabalho é caracterizar o fenótipo ósseo trabecular em pacientes com DM2 e avaliar a influência do tecido adiposo da medula óssea, do acúmulo de gordura muscular e da resistência à insulina sobre o tecido ósseo. Foram realizados exames de espectroscopia por ressonância magnética de coluna lombar, espectroscopia do músculo sóleo e imagem 3D por ressonância magnética na região proximal da tíbia para avaliação de osso trabecular. Exames de densitometria óssea foram realizados para quantificar a massa óssea e também a composição corporal dos indivíduos estudados. O escore trabecular ósseo (TBS) foi analisado na coluna lombar. Foram realizados exames bioquímicos para identificar alterações em potenciais moduladores da remodelação óssea originados em tecidos mesenquimais não mineralizados. Foram avaliados 3 grupos: controle, obeso e diabético tipo 2. Os resultados mostram que os indivíduos diabéticos não possuem prejuízo de massa óssea, nem alterações no trabeculado ósseo da tíbia proximal. Não foi observada alteração no tecido adiposo da medula óssea e não houve relação deste sítio de armazenamento de gordura com a massa óssea. Os resultados mostraram que a massa gorda e os lipídeos intramusculares tiveram relação negativa com o TBS e a massa magra mostrou relação positiva com a densidade mineral óssea. Possivelmente, este é o primeiro estudo na literatura em que se avaliou a estrutura óssea no diabetes melito tipo 2 por meio de ressonância magnética. Os dados reafirmam não haver alterações quantitativas estruturais óssea nesta condição, indicando que a fragilidade óssea observada em estudos populacionais no DM2 se deve provavelmente a prejuízo na qualidade óssea. Este trabalho reforça que a resistência à insulina não tem efeitonegativo sobre a massa óssea. O CTX, a osteocalcina e a adiponectina parecem ter importante papel na determinação dos parâmetros do trabeculado ósseo / Type 2 diabetes is a high prevalence disease and its complications go beyond the cardiovascular diseases. Bone fragility was recently added to the list of the type 2 diabetes complications. Paradoxically, in type 2 diabetes, the bone mass is normal or elevated in comparison to the normoglycemic subjects. Thus, it is necessary to explore other tools to improve the bone evaluation in type 2 diabetes. The aim of this study was to characterize the trabecular bone phenotype in patients with type 2 diabetes and to evaluate the influence of bone marrow adipose tissue, accumulation of muscle fat and insulin resistance in bone mass. Lumbar spine and proximal tibia magnetic resonance spectroscopy was used to quantify bone marrow adipose tissue, 3D imaging by Magnetic Resonance of proximal tibia was used to quantify the trabeculae. Bone densitometry was performed to quantify the bone mineral density and also the body composition. Trabecular bone score (TBS) was measure in lumbar spine. Biochemical tests were carried out to evaluate the potential modulators of bone metabolism. Three groups were evaluated: control, obese and type 2 diabetic. The results show that diabetic individuals have no bone mass impairment and no alterations in the proximal tibia trabeculae. No alteration was observed in the the bone marrow adipose tissue of and there was no relationship of this site of fat storage with the mass. The results showed that fat mass and intramuscular lipids had a negative correlation with TBS, and lean mass showed a positive correlation with bone mineral density. As well as we know, this is the first study in the literature in which the bone structure in type 2 diabetes mellitus was evaluated by magnetic resonance imaging. These data reaffirm that there are no quantitative structural changes in bone in this condition, indicating that the bone fragility observed in DM2 populational studies is probably due to impairment in bone quality. CTX, osteocalcin and adiponectin seems to have an important role in determining in the trabeculae

Bakgrund: Diabetes typ 2 är en av västvärldens vanligaste och växande folksjukdomar. I tidigare forskning framkommer det att den äldre befolkningen med diabetes lever allt längre och är ofta multisjuka. Detta ställer högre krav på distriktssköterskan och ökar komplexiteten i omvårdnaden i hemmet. Syfte: Syftet med studien var att beskriva distriktssköterskors upplevelser av att vårda äldre patienter med diabetes typ 2 i hemsjukvården. Metod: Kvalitativ studiedesign har använts. I studien deltog nio distriktssköterskor i åldrarna 30 till 61 år. Data samlades in genom semistrukturerade intervjuer. Data analyserades med kvalitativ innehållsanalys med en manifest ansats. Resultat: Distriktssköterskorna beskrev betydelsen av ett tvärvetenskapligt tillvägagångssätt som central för att nå en god och säker hemsjukvård och de upplevde att deras arbete hade underlättats om de även samarbetat med en diabetessjuksköterska inom kommunen. Distriktssköterskorna upplevde att tydliga riktlinjer saknades och att arbetsbelastningen och tidsbristen var hög och att det krävdes ökat omvårdnadsansvar och kompetens inom diabetes hos distriktssköterskorna i hemsjukvården. Slutsats: För att säkerställa en god och säker hemsjukvård är det betydelsefullt att kommunen tydliggör riktlinjer för omvårdnaden av patienter med diabetes typ 2 och satsar på att stärka det tvärvetenskapliga samarbetet inom hemsjukvården. / Background: Diabetes type 2 is one of the world's most common and growing public diseases. Current research shows that the elderly population with diabetes lives longer and is often multi-malignant. This places higher demands on the district nurse and increases the complexity of nursing care at home. Purpose: The purpose of the study was to describe district nurses experiences of caring for elderly patients with type 2 diabetes in home care. Method: Qualitative study design has been used. Data was collected through interviews with nine district nurses between the ages 30 and 60 years old with semi-structured interviews. Data was analyzed with qualitative content analysis with a manifest approach. Results: District nurses described the importance of an interdisciplinary approach as central to achieving good and safe home health care and they felt that their work had been facilitated if they also collaborated with a diabetes nurse within the municipality. The district nurses felt that clear guidelines were lacking and that the workload and the lack of time were high and that increased nursing responsibility and competence in diabetes were required at the district nurses in home care. Conclusion: In order to ensure good and safe home health care, it is important that the municipality clarifies guidelines for the care of patients with type 2 diabetes and is investing in strengthening the interdisciplinary cooperation in home care.

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

O pré-condicionamento isquêmico (PCI) é um importante mecanismo de proteção celular, capaz de favorecer a diminuição da necrose dos cardiomiócitos durante isquemia aguda. Fármacos hipoglicemiantes orais, tais como glibenclamida e repaglinida, podem provocar a perda dessa proteção por sua propriedade bloqueadora de canais de potássio dependentes de adenosina trifosfato (K-ATP). Já a vildagliptina, pertencente à classe dos inibidores da enzima dipeptidil peptidase 4 (DPP-4), exerce seus efeitos sobre a glicemia principalmente via hormônio peptídeo-1 tipo glucagon (GLP-1). Receptores de GLP-1 estão presentes no miocárdio e seu papel nesse tecido é alvo de investigadores. Este estudo avaliou o efeito da vildagliptina sobre o pré-condicionamento isquêmico em portadores de diabetes mellitus 2 (DM2) e doença coronariana multiarterial estável (DAC). Foram admitidos 54 pacientes diabéticos com doença multiarterial coronariana estável, documentada pela angiografia e com teste ergométrico positivo para isquemia. Na fase 1, betabloqueadores e fármacos hipoglicemiantes orais foram suspensos por 7 dias, e todos paciente foram submetidos a 2 testes ergométricos (TE) seguenciais, com intervalo de descanso de 30 minutos entre eles (TE1 e TE2). Para a fase 2, os pacientes receberam vildagliptina 100mg/dia por 7 dias consecutivos e foram submetidos a mais 2 TE seguenciais (TE3 e TE4). Na fase 1, todos os pacientes desenvolveram isquemia esforço induzida (depressão de ST>=1 mm) no TE1. O tempo para alcançar 1,0mm de depressão do segmento ST (T-1,0mm) em TE2 foi maior que em TE1, caracterizando a presença do PCI em todos os pacientes. Na fase 2, todos desenvolveram isquemia em TE3, e 76% apresentaram isquemia mais tardia em TE4, isto é, aumentaram a tolerância miocárdica em TE4 em comparação a TE3, caracterizando PCI preservado (p<0,001). Somente 24% dos pacientes revelaram bloqueio do PCI (p=0,006). A vildagliptina preservou o pré-condicionamento isquêmico em pacientes com DM2 e DAC. / Ischemic preconditioning (IPC) refers to the phenomenon in which short periods of myocardial ischemia and reperfusion promote resistance to a subsequent prolonged ischemic insult. Some hypoglycemic drugs, such as glibenclamide and repaglinide, are able to inhibit this protective phenomenon probably by its effects as blockers of adenosine triphosphate-dependent potassium (K-ATP) channels. Moreover, vildagliptin, belonging to the class of dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, performs its action by incretin system, mainly by hormone glucagon-like peptide 1 (GLP-1). GLP-1 receptors are present in various body tissues, including myocardium. Multiple actions of GLP-1 and structurally related GLP-1 agonists have been reported in heart. We aimed to evaluate the effect of vildagliptin on IPC in patients with type 2 diabetes and symptomatic coronary artery disease. We evaluated 54 patients with DM2 and a positive exercise test that also had with multivessel coronary disease confirmed by coronary angiography. In phase I, without drug, all patients underwent 2 consecutive treadmill exercise tests (ET1 and ET2). After that, all patients received vildagliptin 100 mg per day for one week and underwent more 2 more sequential tests (ET3 and ET4). The time interval between the exercises tests was 30 minutes. In phase 1, all patients demonstrated IPC that was observed by the improvement in time to 1mm of ST segment depression (T-1.0mm) in ET2 compared with T1 In phase 2, with vildagliptin, all patients (54) developed ischemia in ET3, however, 76 % (41) of patients showed experienced later ischemia in ET4 compared with ET3 (p<0.001), characterizing IPC preserved. Only 24% (13) patients demonstrated T-1.0mm earlier in ET4 compared with ET3, indicating the cessation of IPC (p=0.006). Vildagliptin did not affect this protective mechanism in a relevant way in patients with type 2 diabetes and symptomatic coronary artery disease.

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.