Bakgrund: Typ 2 diabetes ökar idag bland barn och unga vuxna. Det är viktigt att förstå anledningen till att sjukdomen ökar och vilka åtgärder som krävs för att bromsa utvecklingen. Syfte: Att studera vilka riskfaktorer som beskrivs ha störst påverkan på utveckling av typ 2 diabetes hos barn och unga vuxna samt om och det går att förebygga dessa risker. Metod: En litteraturöversikt baserad på tolv vetenskapliga artiklar. Artiklarna söktes fram i databaserna PubMed och CINAHL. Resultat: Litteraturstudien visade att övervikt och fetma är en av de främsta riskfaktorerna för att utveckla typ 2 diabetes hos barn och unga vuxna. Det mest effektiva sättet att förebygga detta visade sig vara genom regelbunden fysisk aktivitet samt hälsosamma matvanor. Slutsats: Övervikt/fetma är den största riskfaktorn för typ 2 diabetes. Livsstilsändringar i form av ändrad kost samt regelbunden fysisk aktivitet kan förebygga risken att drabbas av diabetes hos barn och unga vuxna som ligger i riskzonen för sjukdomen pga. övervikt/ fetma. Sjuksköterskan har en viktig roll att upptäcka barn och unga i riskzonen och att ge råd om hälsosamma levnadsvanor. / Background: Type 2 diabetes is increasing today among children and young adults. There are different ways of preventing the disease and two of the most effective factors propose to be physical activity as well as healthy eating habits. Objective: The aim of this study was to identify the risk factors described have the greatest impact on development of type 2 diabetes in children and young adults and the most effective ways to prevent the disease. Method: A literature review based on twelve scientific articles. The articles were searched in the PubMed and CINAHL databases. Results: The literature study showed that obesity and being overweight are the major risk factors for developing type 2 diabetes in children and young adults. The most effective way to prevent this was through regular physical activity and healthy eating habits. Conclusion: Obesity and being overweight are the major risk factor for developing type 2 diabetes. Lifestyle changes such as healthy eating habits and regular physical activity can prevent the risk factors in children and young adults at risk of developing the disease. The nurse has an important role in detecting children and young adults at risk and encourage a healthy lifestyle.

L’inflammasome NLRP3, un complexe protéique pro-inflammatoire, joue un rôle essentiel dans le processus pathologique de l’athérosclérose et du diabète de type 2 (DT2). Il est responsable de la maturation de la pro-IL-1β et de la pro-IL-18 respectivement en IL-1β et IL-18 biologiquement actives. L’objectif de cette étude consiste à identifier et caractériser un inhibiteur spécifique de l’inflammasome NLRP3 qui pourrait contribuer à limiter l’évolution des plaques d’athérome et l’installation du DT2. Au cours de cette thèse, nous avons isolé l’Arglabine d’une plante, Artemisia glabella, connue pour ses vertus anti-tumorales. L’effet de l’Arglabine a été étudié au niveau des macrophages et des cellules β-pancréatiques, et chez des souris ApoE2.Ki et ApoE2.Ki/NLRP3-/- placées sous régime High Fat Diet (HFD). Les résultats in vitro montrent que l’Arglabine réduit, d’une façon dose-dépendante, l’activité de l’inflammasome NLRP3 et inhibe l’expression des protéines Nlrp3, IL-1β et caspase-1. Elle induit l’autophagie en augmentant significativement l’expression de la LC3-II au niveau des macrophages murins en culture. L’injection intra-péritonéale de deux doses journalières d’Arglabine (2.5 ng/g de m.c.) à des souris ApoE2.Ki placées sous régime HFD, normalise le profil lipidique et réduit l’oxydation des LDL au niveau du plasma des souris. Elle réduit le nombre des monocytes pro-inflammatoires (Ly-6Chigh) et augmente le nombre des monocytes anti-inflammatoires (Ly-6Clow). Au niveau des lésions artérielles, l’Arglabine oriente les macrophages présents vers un phénotype anti-inflammatoire M2. L’ensemble de ces résultats montre un rôle athéroprotecteur de l’Arglabine : elle réduit la surface des lésions artérielles au niveau du sinus aortique ainsi qu’au niveau de la totalité de l’aorte des souris ApoE2.Ki placées sous régime athérogène. De plus, le traitement par l’Arglabine normalise le profil glycémique et insulinémique des souris ApoE2.Ki. Elle réduit également l’activité de la caspase 3 au niveau des îlots de Langerhans et augmente de manière dose-dépendante l’expression de la protéine Bcl-2 au niveau des cellules β-pancréatiques. Par ailleurs, nous avons montré une augmentation de l’expression de protéines impliquées dans l’autophagie telles que la Becline 1 et la LC3-II sous l’effet de l’Arglabine. Ainsi, l’Arglabine réduit non seulement l’activité de l’inflammasome NLRP3 mais améliore aussi la survie des cellules β-pancréatiques. L’Arglabine constitue donc une molécule très prometteuse dans le traitement des maladies cardiovasculaires et le DT2. / The NLRP3 inflammasome activity is abnormally elevated in many human inflammatory diseases, including cardiovascular and metabolic diseases such as atherosclerosis and type 2 diabetes mellitus (T2DM) respectively. Therefore, there is considerable interest in the identification of effective therapeutics that selectively inhibit the NLRP3 inflammasome pathway. In this study, we have identified Arglabin as a potential small molecule inhibitor that targets the NLRP3 inflammasome activity in cell culture and in an animal model, the ApoE2.Ki mice fed a high-fat Western-type diet (HFD). Arglabin, a plant sesquiterpene lactone, has been used extensively as an herbal remedy that proved effective in treating cancer of the liver, lungs and breast at early stages. Arglabin inhibited, in a concentration-dependent manner, IL-1β and IL-18 production in lipopolysaccharide and cholesterol crystal-activated cultured mouse peritoneal macrophages. In addition, Arglabin activated autophagy as evidenced by the increase in LC3-II protein. Intraperitoneal injection of Arglabin (2.5 ng/g body weight twice daily for 13 weeks) into female ApoE2.Ki mice fed a HFD resulted in a decreased IL-1β plasma level and reduced plasma levels of total cholesterol and triglycerides. Treatment of ApoE2.Ki mice fed a HFD with Arglabin significantly reduced the plasma concentration of anti-oxLDL antibodies. Moreover, Arglabin oriented the proinflammatory M1 macrophages into the anti-inflammatory M2 phenotype in spleen and arterial lesions. Consequently, a marked reduction in atherosclerotic lesions was observed in the median areas in the sinus and whole aorta. In comparison to vehicle-treated mice, Arglabin reduced plasma levels of glucose and insulin. Immunohistochemical analysis revealed the presence of active caspase 3 in Langerhans islets of ApoE2.Ki mice fed a HFD that was significantly inhibited by Arglabin treatment. Moreover, Arglabin reduced susceptibility to apoptosis in cultured INS-1 cells by increasing concentration-dependently Bcl-2 levels, which led to concomitantly decreased Bax/Bcl-2 ratio. In cultured INS-1 cells, Arglabin increased the expression of the autophagic markers Becline 1 and LC3-II in a concentration-dependent manner. Consequently, our results indicate survival-promoting properties of the Arglabin molecule in pancreatic β-cells.In conclusion, our findings demonstrate that Arglabin may represent a promising new drug to treat atherosclerosis and T2DM.

The purpose of this thesis was to aid in the development of a web-based physical activity intervention for people with type 2 diabetes living in remote and rural areas. Chapter 1 introduces the research area, the design of the thesis and the key research questions. The thesis is then made up of 5 key studies. Study one, a systematic review of the literature was conducted and reported in chapter 2. This review identified the technologies that have previously been used to promote physical activity in type 2 diabetes, it identified the methodological quality of each included technology and the key components for effective change. Web based technology was the most commonly used and the most effective in increasing physical activity using components such as goal setting and physical activity trackers. These results informed study 2 (chapter 3) which explored patient and health professional's views on diabetes, physical activity and use of the internet. The need for clear information was identified with regard to diabetes as well as the call for accurate physical activity advice in relation to diabetes for both patients and health professionals. Study 3 (chapter 4) explored key information and components for an effective website. Included features were the need for a personalised approach; detailed advice on how the body responds to physical activity; a physical activity tracker and goal setting. The need for a 'virtual trainer' for support, advice and help with goal setting and interactive maps showing physical activity opportunities were all deemed important. The fourth study, chapter 5 described the design of the website and its features as well as the protocol for a six month pilot randomised controlled trial to examine the effectiveness of the development website, with and without interactive design elements. The final study in this thesis (chapter 6), describes the physical activity, physiological and biochemical results from a randomised controlled trial to test the effectiveness of the website and its features. The final chapter summarises the findings in response to the research questions and the future recommendations based on the outcomes.

Genetic heterogeneity, lifestyle factors, gene-gene or gene-environment interactions are the determinants of T2D which puts Hispanics and populations with African ancestry at higher risk of developing T2D. In this dissertation, the genetic associations of PPARGC1A polymorphisms with T2D and its related phenotypes (metabolic markers) in Haitian Americans (cases=110, controls=116), African Americans (cases=120, controls=124) and Cuban Americans (cases=160, controls=181) of South Florida were explored. Five single nucleotide polymorphisms of gene PPARGC1A were evaluated in each ethnicity for their disease association. In Haitian Americans, rs7656250 (OR= 0.22, pp=0.03) had significant protective association with T2D but had risk association in African Americans for rs7656250 (OR=1.02, p=0.96) and rs4235308 (OR=2.53, p=0.03). We found that in Haitian American females, both rs7656250 (OR=0.23, pp=0.03) had protective association with T2D. In African American females, rs7656250 (OR=1.14, p=0.78) had risk association whereas in males, it had significant protective effect (OR=0.37, p=0.04). However, the risk association exhibited by rs4235308 was stronger in African American females (OR=2.69, p=0.03) than males (OR=1.16, p=0.72). In Cuban Americans, only rs7656250 showed significant risk association with T2D (OR=6.87, p=0.02) which was stronger in females alone (OR=7.67, p=0.01). We also observed significant differences among correlations of PPARGC1A SNPs and T2D phenotypes. Positive correlation was observed for log Hs-CRP with rs3774907 (pp=0.03) in Cuban Americans respectively. Correlation of log A1C with rs7656250 (p=0.02) was positive in Cuban Americans while it was negative for rs3774907 in Haitian Americans (ppPPARGC1A correlations with T2D and its phenotypes among the three ethnicities studied (ii) the associations of PPARGC1A SNPs showed significant effect modification by sex. The findings suggest that variations in effects of PPARGC1A gene polymorphisms among three ethnicities and between sexes may have biomedical implications for the development of T2D as well as the phenotypes related to T2D.

La mortalité du diabète de type 2 est liée à ses complications cardiovasculaires (CVD). L'identification de nouveaux biomarqueurs associés à la dysfonction endothéliale, permettrait d'en améliorer le dépistage, la prévention. Au cours du diabète de type 2, l'hyperglycémie est associée à un fort stress oxydant. Nous nous sommes proposés ici d'évaluer l'impact de la glycoxydation sur la principale protéine circulante, l'albumine, et d'identifier si les modifications glycoxydatives de l'albumine dans le diabète avait un rôle dans la phyiopathologie des CVD du diabète de type 2. Nous avons pu mettre en évidence des modifications structurales et fonctionnelles importantes de l'albumine au cours du diabète de type 2 avec la formation entre autres de produits avancés de glycation (AGEs). Ces modifications glycoxydatives sont associées à des effets cellulaires pro-oxydant et pro-inflammatoire via une augmentation de l'expression du Récepteur aux AGEs (RAGE). Ces observations suggèrent que les formes glycoxydées d'albumine présentent un rôle central dans les mécanismes menant à la dysfonction endothélilale. Il reste néanmoins à évaluer l'intérêt du dosage des formes modifiées de l'albumine dans le dépistage des CVD au cours d'une étude clinique prospective de grande ampleur. Le développement d'une méthode de dosage rapide et reproductible des fractions d'albumine modifiées, comme celui de l'IMA (albumine modifiée par l'ischémie), en faciliterait la mise en œuvre. / Type 2 diabetes is dramatically associated with an enhanced cardiovascular complication risk. The identification of novel biomarkers associated with endothelial dysfunction remains highly warranted to improve diabetes screening and prevention. Oxidative stress and protein modifications are frequently observed in numerous disease states. Albumin, the major circulating protein in blood, can undergo increased glycoxidation in diabetes. Objectives of my thesis were to clarify the impact of glycoxidative modification of albumin on its structure and its functions and to determine whether such impairments may be encountered in albumin purified from diabetics. The occurrence of oxidative modifications was found to be enhanced in in vitro glycoxidized HAS and albumin purified from diabetics, after determination of their free thiol group content, relative electrophoretic migration, carbonyl content, and antioxidant activities. In addition, glycoxidized albumin exhibited impaired pharmaceutic molecule binding capacities. Cells treated with glycoxidized albumin exhibited a proinflammatory state attested by an overgeneration of intracellular reactive oxygen species, enhancements in RAGE expression, and an accumulation of carbonylated proteins.Methods to detect IMA (ischemia modified albumin) were developed and applied to diabetics patients. Relationships have been established between specific pathological parameters (cardiovascular disorders, hyperglycemia…) with an enhanced glycoxidative modification of albumin in diabetics. We thus propose that impaired albumin structure and function in relation in the enhanced oxidant stress observed in diabetics might be involved in the increased mortality risk of these patients.

Many diseases are caused by proteins or peptides folding incorrectly and aggregating into fibrils or plaques, including Alzheimer’s disease, Parkinson's disease and type II diabetes. Amyloid formation in the human pancreas occurs via the aggregation of a 37 amino acid peptide called amylin or IAPP which is shown to be toxic to pancreatic β cells. Amylin (IAPP) aggregation initiates a large number of events, leading ultimately to cell death. However the exact cytotoxic action of human IAPP and also the underlying molecular events leading from amylin (IAPP) aggregation to β cell death is still unknown. The toxic effect of human amylin (IAPP) is thought to involve changes in the expression of several genes and proteins. Further transcriptional and proteomics studies in this field can therefore facilitate the identifications of new targets whose expression are affected by amylin (IAPP). These information could be further used to construct an integrated model of the signalling and regulatory pathways through which amylin (IAPP) interacts with cellular metabolism.To investigate the effects of amylin (IAPP) aggregation on the islets proteome in this study, rat Rin-5F cell line, reported as a model of pancreatic β cell, was used. MTT assay was initially performed to determine the effect of IAPP on the cell viability at different time points. The isolated proteins form the untreated and IAPP treated Rin-5F cells were then fractionated by off gel electrophoresis and analysed by quantitative label free LC- MS/MS approach.Label free quantification of IAPP treated Rin-5F cells has identified the altered expression of many proteins, some of which were previously suggested in the literature to be involved in the pathogenesis of type 2 diabetes. These proteins were map to several pathways (including glycolysis and proteasome) whose expressions were significantly affected upon amylin (IAPP) exposure. The IAPP responsive proteins were also structured into a well connected network. Some of the hub proteins identified in this network were greatly affected as the result of IAPP treatments of RIN-5F cells. Our data therefore revealed the effect of IAPP on several proteins and pathways that might be important in the pathogenesis of type 2 diabetes.

Insulin resistance, a key risk factor for type 2 diabetes, can be defined as when cells fail to respond effectively to insulin. In striated muscle and fat, this manifests as impaired insulin-stimulated glucose uptake due to reduced plasma membrane insertion of the glucose transporter GLUT4. In cell culture models, insulin resistance induced by chronic exposure to insulin, endothelin-1 or glucosamine, is correlated with reduced immunoreactivity of the lipid phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) in plasma membrane sheets. However, the reason for this decrease, and whether other factors that induce insulin resistance affect PtdIns(4,5)P2 levels, is unknown. Using L6 skeletal muscle myotubes and 3T3-L1 adipocytes, this project has investigated whether PtdIns(4,5)P2 levels are perturbed in insulin resistance induced by several factors, including exposure to insulin, oxidative stress, and treatment with tumour necrosis factor α, endothelin-1 or angiotensin II (Ang II).All these pre-treatments were found to abolish insulin-stimulated 3H 2-deoxy-glucose uptake, and significantly decrease PtdIns(4,5)P2 levels, measured in cell extracts by quantitative blotting using a PtdIns(4,5)P2-specific probe, developed from the PH domain of phospholipase C (PLC) δ. Importantly the ability of insulin to stimulate glucose uptake can be restored by replenishing PtdIns(4,5)P2 in L6 myotubes treated with insulin and Ang II. PtdIns(4,5)P2 levels are regulated by three families of proteins; PIP kinases, which synthesise it, phosphatases, which remove phosphate groups from the inositol headgroup, and PLCs, which hydrolyse it. Membrane preparations from Ang II- and insulin-induced insulin resistant L6 myotubes showed no differences in PtdIns(4,5)P2 production or dephosphorylation. However a significant increase in PLC activity was detected in membranes from insulin resistant cells and membrane localisation of PLCβ family members was increased in insulin resistant cells. Furthermore, studies using PLC inhibitors show a restoration of PtdIns(4,5)P2 levels in insulin resistant cells, leading to partial reversal of insulin resistance.This study therefore shows a causal link between decreased PtdIns(4,5)P2 levels and insulin resistance in L6 myotubes, and that PLCs are the reason for the PtdIns(4,5)P2 decrease in Ang II- and insulin-induced insulin resistance. PLCs, or their activation pathways, may thus be a novel target for combating insulin resistance, and preventing type 2 diabetes.

O objetivo do presente estudo foi avaliar o papel do treinamento físico aeróbio, resistido ou combinado (aeróbio+resistido) no desenvolvimento do diabetes tipo 2 analisando mecanismos associados às complicações no diabetes em camundongos fêmeas com deficiência na produção leptina (ob/ob). Para tanto, foram utilizadas camundongos fêmeas, inicialmente com 4 semanas de idade, divididas em 6 grupos: ob/ob sedentárias com 4 semanas de vida (OS-4), selvagens sedentárias (SS) ou ob/ob sedentárias (OS-12) acompanhadas até a 12ª semana de vida, ob/ob treinamento aeróbio (OA), ob/ob treinamento resistido (OR) e ob/ob treinamento combinado (OC). Os grupos treinados foram submetidos a 8 semanas de treinamento físico dinâmico aeróbio em esteira (50 a 60% da velocidade máxima do teste de esforço) ou resistido em escada (4060% da carga máxima) ou a associação dos dois treinos (combinado). Foram avaliados: peso corporal; glicose, triglicérides e colesterol total sanguíneos; pressão arterial (PA) e frequência cardíaca (FC); sensibilidade barorreflexa (SBR); modulação autonômica cardiovascular; marcadores inflamatórios e hormonais; e parâmetros de estresse oxidativo. Os animais obesos (OS-12) apresentaram aumento de peso corporal, tecido adiposo, de glicemia, de triglicérides e de intolerância à glicose quando comparado aos animais selvagens (SS). Adicionalmente, o grupo OS-12 apresentou piores resultados nos testes aeróbio e de força. Não observamos diferenças entre os grupos SS e OS-12 em relação a PA e FC, porém o grupo OS-12 apresentou diminuição da variabilidade da frequência cardíaca (VFC) (33 ± 4ms2) e da sensibilidade barorreflexa em relação ao grupo SS (VFC: 178 ± 19 ms2). O grupo OS-12 apresentou aumento de angiotensina 2 nos tecidos renal e cardíaco, diminuição da adiponectina e aumento de citocinas inflamatórias no tecido adiposo e no baço em relação ao grupo SS. Somado a isso, os animais obesos apresentam maior dano a proteínas e lipoperoxidação e diminuição das enzimas antioxidantes em tecido renal e cardíaco em relação ao grupo SS. A comparação entre os grupos OS-4 e OS-12 evidenciou aumento de peso corporal, tecido adiposo, glicemia, intolerância à glicose e de parâmetros de estresse oxidativo no grupo OS-12 em relação ao grupo OS-4. A redução na VFC e na SBR foi observada no grupo OS-4 e no grupo OS-12. O treinamento físico por sua vez, diminuiu o ganho de peso e reduziu a glicemia e a intolerância à glicose nos três grupos treinados em comparação ao grupo OS-12. O treinamento físico aeróbio (61 ± 8ms2 e 6 ± 4 mmHg2) e resistido (66 ± 16ms2 e 6 ± 1,4mmHg2) foram eficientes em aumentar a VFC e diminuir a banda de baixa frequência da PA (simpático vascular) em relação ao grupo OS-12, porém o grupo OC (43 ± 7ms2 e 8 ± 0,9mmHg2) foi semelhante ao grupo OS-12 (10 ± 1,1mmHg2) e aos grupos OA e OR. Além disso, as três modalidades melhoraram a SBR. Os três tipos de treinamento reduziram os níveis de angiotensina 2 e aumentaram os níveis de angiotensina 1-7 em tecido adiposo, rim e coração. O treinamento físico aeróbio foi mais eficiente em melhorar o perfil inflamatório em tecido adiposo e no baço, uma vez que os grupos OA e OC apresentaram aumento de adiponectina e apenas o grupo OC apresentou diminuição de IL-6 e PAI-1 em relação ao grupo OS-12. Em relação ao estresse oxidativo, os três grupos treinados apresentaram diminuição de marcadores de lesão. Concluindo, nossos achados confirmam o desenvolvimento de disfunção metabólica ao longo da vida de camundongos ob/ob. É interessante notar que com 4 semanas de vida camundongos ob/ob apresentaram uma expressiva redução dos parâmetros da VFC. Este desbalanço autonômico, poderiam estar ocorrendo não só no coração, mas para outros tecidos, como o baço e o tecido adiposo, favorecendo a liberação de citocinas inflamatórias que poderiam induzir a longo prazo lesão de órgão alvo, como observado no presente estudo em coração e rins, por aumento de estresse oxidativo. Os grupos treinados, independente da modalidade, apresentaram melhora metabólica e na regulação autonômica cardiovascular, a qual foi acompanhada de alterações favoráveis no sistema renina-angiotensina, em mediadores inflamatórios e no perfil de estresse oxidativo. Neste sentido, acreditamos que a atenuação da disfunção autonômica (precocemente observada neste modelo de DM) pelo treinamento físico, independente do tipo, possa induzir alterações favoráveis (e dependentes do tipo de treino) no sistema renina angiotensina e em mediadores inflamatórios, reduzindo o estresse oxidativo em tecidos importantes para a regulação cardiovascular / The aim of this study was to evaluate the role of aerobic, resistance or combined (aerobic + resistance) exercise training in the development of type 2 diabetes, analyzing mechanisms associated with diabetes complications in female mice with deficiency in leptin production (ob/ob). Female mice, initially with 4 weeks of age, were divided into 6 groups: ob/ob sedentary with 4 weeks of life (OS-4), sedentary wild type (SS) or ob/ob sedentary (OS-12) followed until 12 week life, ob/ob+aerobic training (OA), ob/ob+resistance training (OR) and ob/ob+combined training (OC). The trained groups were submitted to eight weeks of dynamic aerobic exercise training on a treadmill (50-60% of maximum stress test speed) or resistance exercise on a ladder (40-60% of the maximum load) or an association of these two trainings (combined). Body weight; glucose, triglycerides, and total blood cholesterol; blood pressure (BP) and heart rate (HR); baroreflex sensitivity (BRS); cardiovascular autonomic modulation; inflammatory and hormonal markers; and oxidative stress parameters were evaluated. Obese animals (OS-12) showed increased body and fat weight, blood glucose, triglyceride and glucose intolerance when compared to wild type animals (SS). Additionally, OS-12 group showed decreased capacity in aerobic and strength exercise tests. We did not observe differences between the SS and the OS-12 groups regarding BP and HR, however the OS-12 group showed reduced heart rate variability (HRV) (33 ± 4ms2) and baroreflex sensitivity when compared to the SS group (178 ± 19 ms2). The OS-12 group showed increased angiotensin 2 in kidney and heart tissues, decreased adiponectin and increased inflammatory cytokines in adipose tissue and in the spleen in relation to the SS group. Moreover, obese animals presented increased protein oxidation and lipid peroxidation and decreased antioxidant enzymes in kidney and heart tissues when compared to SS group. The comparison between the OS-4 and the OS-12 groups showed increased body and fat weight, blood glucose, glucose intolerance and oxidative stress in OS-12 compared to OS-4 group. The decrease in HRV and in BRS were observed in OS-4 and OS-12 groups. On the other hand, exercise training decreased weight gain and reduced blood glucose and glucose intolerance in all three trained groups compared to OS-12 group. Aerobic (61 ± 8ms2 and 6 ± 4 mmHg2) and resistance exercise training (66 ± 16ms2 and 6 ± 1.4mmHg2) were efficient in increasing the HRV and decrease the low frequency band of BP (vascular sympathetic modulation) as compared to OS-12 group; however OC group (43 ± 7ms2 and 8 ± 0.9mmHg2) was similar to OS-12 group (10±1.1mmHg2) and to OA and OR groups. In addition, the three types of exercsie training improved BRS. The three types of training reduced levels of angiotensin 2 and increased levels of angiotensin 1-7 in adipose tissue, kidney and heart. The aerobic exercise was more efficient in improving inflammatory profile in adipose tissue and spleen, since OA and OC groups showed an increase in adiponectin and only the OC group showed a decrease in IL-6 and PAI-1 in relation to the group OS-12. Regarding oxidative stress, the three trained groups showed a decrease in damage markers. In conclusion, our findings support the development of metabolic dysfunction during lifespan in ob/ob mice. Interestingly, 4 weeks old ob/ob mice showed a significant reduction in HRV parameters. This autonomic imbalance could be occurring not only in the heart, but in other tissues, such as the spleen and the adipose tissue, promoting the release of inflammatory cytokines. These cytokines could induce long-term target organ damage, as observed in this study in heart and kidney by increased oxidative stress. The trained groups, regardless of the type of training, showed improved metabolic and cardiovascular autonomic regulation, which were accompanied by favorable changes in the renin-angiotensin system, inflammatory mediators and oxidative stress profile. In this sense, we believe that the attenuation of autonomic dysfunction (early observed in this model of DM) by exercise training, regardless of the type of training, can induce positive changes (dependent on the type of exercise training) on the renin angiotensin system and inflammatory mediators, reducing oxidative stress in important tissues for cardiovascular regulation

Bakgrund: Typ 2-diabetes är en vanlig förekommande sjukdom hos befolkning i Sverige som kan påverkas av olika faktorer såsom stress, fysisk inaktivitet och kost. Egenvård vid typ 2-diabetes är en viktig del av behandling. Därför ska patientens upplevelse av egenvård studeras för att skapa en omsorgsfull relation med patienten och för att kunna stödja de att klara sitt omvårdnadsbehov på egen hand. Syfte: Författarna vill i denna litteraturstudie beskriva patientens erfarenhet av egenvård vid typ 2-diabetes. Metod: Studien har utförts som en kvalitativ litteraturstudie. Tio vetenskapliga artiklar inkluderades. Artiklarna söktes via databaserna CHINAL och Pub Med. Artiklar med kvalitativ ansats var inkluderades. Resultatet bearbetades, analyserades och sammanställdes. Resultat: Resultaten i studien visar på att patientens med typ 2-diabetes har olika upplevelser som påverkas av olika faktorer och dessa har kategoriserats i tabellen med fyra kategorier och nio underkategorier: 1) Undervisning: Gruppundervisning, 2) Attityd. Kunskap: Teoretisk och praktisk kunskap, 3) Barriärer: Glykemisk kontroll, omgivningen, Brist på motivation, 4) Kännedom: Kost, fysisk aktivitet Konklusion: patienten med typ 2-diabetes behöver insatser och stöd i form av undervisning, information, familjens och vännernas stöd för att kunna hantera sin diabetes. Kunskapsbrist om typ 2-diabetes i personers omgivning påverkar patientens egenvård. Information av dessa kunskapsbrister är ett verktyg som underlättar sjuksköterskans arbete. / Background: The number for people with Type 2-diabetes disease is increasing in Sweden and the disease is affected by various factors such as stress, physical inactivity and diet. Self-care at Type 2-diabetes is an important part of treatment. We therefore seek to study patient experience of self-care to create a careful relationship with the patient and to support them to cope with their nursing needs on their own. Purpose: The authors want to describe in this literature review the patient's self-care experience in type 2 diabetes. Method: The study has been conducted as qualitative literature review. Ten scientific articles were included. The articles were searched through the CHINAL and Pub Med databases. The study included only qualitative articles. The result was processed, analyzed and compiled. Results: The results in the study show that the patient with Type 2-diabetes has different experiences that are influenced by different factors and these have been categorized in the table with four main themes and nine subthemes: 1) Teaching: Group teaching, 2) Attitude. Knowledge: Theoretical Practical, 3) Barriers: Glycemic Control, Environment, Lack of Motivation, 4) Knowledge: Diet, Physical Activity. Conclusion: The patient with Type 2-diabetes needs assistance and support in the form of education, information, family and friends support to manage their diabetes. A lack of knowledge about Type 2-diabetes in people's surroundings affects patient rehabilitation. Information of these knowledge shortages is a tool that facilitates the nurse's work.

La prévalence du diabète de type 2 ne cesse d’augmenter et la tranche d’âge des plus de 65 ans subit la hausse la plus importante. Des différences liées au genre ont été rapportées entre les hommes et les femmes diabétiques de type 2, notamment en ce qui concerne les complications macrovasculaires du diabète mais il n’y a pas, à notre connaissance, d’étude française qui s’est spécialement intéressée à cette question. La majorité des études internationales ne se sont pas intéressées aux sujets âgés mais à toute la population diabétique et beaucoup d’entre elles sont anciennes, datant d’avant l’introduction des nouveaux traitements cardiovasculaires avec un fort niveau de preuve.Ce travail avait comme objectif d’évaluer l’existence de différences liées au genre dans la prise en charge du diabète de type 2 au sein d’une population contemporaine de sujets âgés pris en charge en conditions de vie réelle en soins primaires. Les objectifs spécifiques étaient de comparer l’équilibre du diabète et le contrôle des facteurs de risque cardiovasculaire et la survenue d’événements cliniques majeurs (décès ou événement cardiovasculaire majeur, hospitalisation) entre les hommes et les femmes, et d’évaluer le rôle du genre du médecin traitant dans ces différences potentielles.La cohorte S. AGES diabète de type 2 est une étude observationnelle prospective de sujets âgés de 65 ans ou plus, non institutionnalisés, ayant un diabète de type 2. Au total 983 patients ont été inclus entre avril 2009 et juin 2011 par 213 médecins. L’évolution clinique et la survenue d’événements majeurs ont été renseignées pendant 3 ans. Des modèles mixtes ont été utilisés dans les analyses statistiques en raison de la corrélation entre les mesures répétées du même patient et la corrélation entre les patients du même médecin.Pendant toute la période du suivi, l’équilibre du diabète de type 2, estimé par l’hémoglobine glyquée HbA1c, n’était pas différent entre les hommes et les femmes, le contrôle de la pression artérielle était meilleur chez les hommes que chez les femmes en analyse bivariée mais pas en analyse multivariée. Par contre, le contrôle du cholestérol LDL était meilleur chez les hommes que chez les femmes avec un risque relatif pour les femmes par rapport aux hommes d’avoir un LDL non contrôlé (>1 g/l) de 2,56 (IC à 95 % 1,82-3,59 ; p<0,001). Cette différence était présente dans le groupe traité par statines ainsi que dans le groupe non traité.En ce qui concerne la survenue d’événements cliniques majeurs, les femmes avaient un risque plus faible de développer un événement clinique majeur (décès toutes causes confondues, événement cardiovasculaire majeur) par rapport aux hommes avec un risque relatif de 0,60 (IC à 95 % 0,40-0,91 ; p= 0.016) ou d’être hospitalisées avec un risque relatif de 0,71 (IC à 95 % 0,52-0,96, p=0,029). La majorité des hospitalisations était liée aux pathologies concomitantes autres que le diabète, surtout chez les hommes qui étaient davantage admis en CHU/CHR que les femmes. Le risque de développer des complications microvasculaires du diabète n’est pas différent entre les hommes et les femmes.Enfin, nos analyses n’ont pas montré de différence entre les médecins hommes et les médecins femmes au niveau du contrôle des facteurs de risque cardiovasculaire, de la réalisation d’examens de surveillance, de dépistage des complications, ni de prescription de traitements antidiabétiques et cardiovasculaires.Nos résultats montrent que les différences liées au genre dans cette population de patients diabétiques âgés sont réservées à un cholestérol LDL plus élevé chez les femmes que chez les hommes, mais qui ne s’accompagne pas d’une augmentation du risque de survenue d’événements cliniques majeurs (qui reste plus élevé chez les hommes). Cependant il faut interpréter ces résultats dans le contexte de la cohorte S.AGES avec des biais de sélection au niveau médecin et au niveau patient ainsi qu’une sous-représentation des médecins femmes. / The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide and this trend is projected to persist because of the demographic shift and the obesity pandemic. The elderly represent more than half of subjects with T2DM and this proportion is expected to increase in the future. Cardiovascular disease is the main cause of morbidity and mortality in elderly subjects with T2DM. Moreover, although non-diabetic women have lower risk of developing cardiovascular diseases compared to non-diabetic men of the same age, this “female advantage” seems to diminish or disappear in the setting of T2DM. Indeed, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to gender. To the best of our knowledge, there is no French study that had looked at this issue. The majority of international studies have not focused on the elderly group but on the whole diabetic population and many of them are conducted before the introduction of evidence-based cardiovascular treatments.The aim of the present work was to assess gender-related differences in the management of elderly patients with T2DM followed-up in the primary care. Specifically, we compared the control of T2DM and other cardiovascular risk factors between women and men, the occurrence of major clinical events (all-cause mortality and major vascular events as well as all-cause hospitalization) between women and men, and the influence of physician gender on the quality of care in subjects with T2DM.The S.AGES T2DM cohort is a prospective observational study whose objective was to describe the real-life medical management of subjects aged 65 years or more with T2DM. 983 non institutionalized subjects were included by 213 general practitioners from April 2009 through June 2011 and followed-up for 3 years. For data obtained during the follow-up period, multilevel mixed-effect regression models were used to account for repeated measurements (for each subject) and clustering (A cluster is a group of subjects followed-up by the same GP).Over the follow-up period, T2DM and blood pressure control were not different between the genders but LDL cholesterol was better controlled in men than in women. The odds ratio for women being associated with uncontrolled LDL cholesterol (>1 g/l) was 2.51 (95% CI 1.79–3.53, p<0.001). This gender-related difference in LDL cholesterol levels was independent of statin therapy.Concerning major clinical events, women were at lower risk than men to develop the composite endpoint (all-cause mortality and major vascular events) with a relative risk of 0.60 (95% CI 0.40-0.91, p=0.016) and the hospitalization endpoint (OR 0.71, 95% CI 0.52-0.96, p=0.029). Coexisting diseases were responsible to the majority of hospitalizations especially in men who were more likely to be admitted to a university hospital when compared to female counterparts. The risk of developing microvascular complications and hypoglycemia were not different between men and women.Finally, we didn’t find any significant difference between male and female physicians in terms of quality of care in subjects with T2DM (control of T2DM and other cardiovascular risk factors, tests to screen for diabetes complications, or the prescription of anti-diabetic and cardiovascular treatments).Our results show that gender differences in this population of elderly diabetics are restricted to higher LDL cholesterol in women than in men but this does not seem to increase the risk of major clinical events (which are higher in male subjects). However, these results should be interpreted with cautious because of selection biases at the physician and patient level as well as under-representation of female physicians.