Dem Spurenelement Chrom wird seit mehreren Jahrzehnten eine maßgebliche Funktion im Glucosestoffwechsel zugeschrieben. In der vorliegenden placebokontrollierten Studie wurden die Effekte einer Chromhefezulage bei insulinresistenten Ponies und Pferden untersucht. Aus dem Patientenklientel der Pferdeklinik an der Rennbahn wurden mittels eines Stärketoleranztest 27 Ponies und Pferde ausgewählt, welche einen veränderten Glucosestoffwechsel aufwiesen. Die Versuchsprobanden waren 13,9 ± 4,8 Jahre alt, wiesen eine mittlere Körpermasse von 422 ± 138 kg und einen mittleren Body Condition Score von 7,6 ± 0,8 (Skala 1-9) auf. Die 27 Ponies und Pferde wurden nach dem Zufallsprinzip in 2 Gruppen unterteilt. Die Chromgruppe (N=15) erhielt über einen Zeitraum von 28 ± 7 Tagen eine Chromhefezulage in einer täglichen Dosierung von 25 μg/kg KM, die Placebogruppe (N=12) erhielt eine Hefezulage ohne Chrom in derselben Hefemenge wie die Chromgruppe. Während des Versuchszeitraumes wurden alle Probanden mit Heu 1,5 kg /100 kg KM gefüttert. Zu Beginn und am Ende des Versuchszeitraumes wurde jeweils ein Stärketoleranztest (1,5 g Stärke/kg KM) über eine Dauer von 420 min durchgeführt. Die Blutproben wurden postprandial in definierten Intervallen entnommen. In beiden Gruppen konnte ein deutlicher Gewichtsverlust über die vierwöchige Versuchszeit beobachtet werden. Dabei wurde ein signifikanter Gewichtsverlust bei der chromsupplementierten Gruppe von 3,8 ± 4,3 % (p < 0,05) und ein ebenfalls signifikanter Gewichtsverlust bei der Placebogruppe von 2,1 ± 3,2 % (p < 0,05) verzeichnet. Unterschiede zwischen den Behandlungsgruppen konnten aber nicht mit p < 0,05 abgesichert werden. Die Ruheglucosekonzentrationen bewegten sich bei den chromsupplementierten Tieren im Mittel bei 6,3 ± 2,1 mmol/l, die placebosupplementierte Gruppe wies mittlere Werte von 5,5 ± 0,9 mmol/l auf. Nach der Behandlung konnten Ruheglucosekonzentrationen von 6,0 ± 2,0 mmol/l für die chromsupplementierten Tiere und Ruheglucosekonzentrationen von 5,6 ± 0,5 mmol/l für die placebosupplementierten Probanden gemessen werden. Die Nüchterninsulinkonzentrationen im Plasma lagen vor der Supplementierung bei 63,7 ± 81,9 μU/ml für die Chromgruppe und bei 42,9 ± 47,8 μU/ml für die Placebogruppe. Nach der Behandlung konnten Nüchterinsulinkonzentrationen bei den chromsupplementierten Pferden und Ponies von 33,2 ± 35,7 μU/ml sowie bei den placebosupplementierten Tieren von 14,4 ± 8,7 μU/ml verzeichnet werden. Diese Veränderung der Nüchterninsulinwerte innerhalb der beiden Behandlungsgruppen war jedoch nicht signifikant. Beim 1. Stärketoleranztest erreichte die Chromgruppe eine mittlere maximale Plasmaglucosekonzentration von 12,4 ± 2,6 mmol/l mit Einzelwerten bis zu 19,3 mmol/l, die Placebogruppe wies eine mittlere maximale Plasmaglucosekonzentration von 11,8 ± 2,0 mmol/l mit Einzelwerten bis 16,3 mmol/l auf. Die Plasmainsulinkonzentrationen stiegen im 1. Stärketoleranztest bei der Chromgruppe auf mittlere maximale Werte von 1902 ± 1393 μU /ml sowie in der Placebogruppe auf 1158 ± 753 μU/ml. Im 2. Stärketoleranztest erreichte die Chromgruppe eine mittlere maximale Plasmaglucosekonzentration von 11,0 ± 3,0 mmol/l und die Placebogruppe wies eine mittlere maximale Plasmaglucosekonzentration von 10,7 ± 2,6 mmol/l auf (Behandlung und Zeit: nicht signifikant). Die Plasmainsulinkonzentrationen der Chromgruppe stiegen im 2. Stärketoleranztest auf mittlere maximale Plasamainsulinkonzentrationen von 1277 ± 856 μU/ml, für die placebosupplementierte Gruppe wurden mittlere Maximalwerte von 883 ± 725 μU/ml ermittelt; diese Unterschiede waren jedoch nicht signifikant. Der beobachtete Körpergewichtsverlust scheint für beide Gruppen von Bedeutung für die Verbesserung der Insulinresistenz zu sein. Nach der vierwöchigen Supplementierungsphase konnte allerdings bei den Tieren die Cr erhielten, eine deutlichere Reduktion bei der Insulinreaktion im Verlaufe des 2. STT beobachtet werden, wohingegen die Placebopferde nur eine moderate Veränderung in der Insulinreaktion aufwiesen.

Despite major advances in the treatment and prevention of atherosclerosis the last several decades, cardiovascular disease still accounts for the majority of deaths in Sweden. With the population getting older, more obese and with rising numbers of diabetics, the cardiovascular disease burden may increase further in the future. The focus in cardiovascular disease has shifted with time from calcification and narrowing of arteries to the biological processes within the atherosclerotic plaque. C-reactive protein (CRP) has emerged as one of many proteins that reflect a low grade systemic inflammation and is suitable for analysis as it is more stable and easily measured than most other inflammatory markers. Several large prospective studies have shown that CRP is not only an inflammatory marker, but even a predictive marker for cardiovascular disease. C-reactive protein is associated with several other risk factors for cardiovascular disease including obesity and the metabolic syndrome. Our study of twenty healthy men during a two week endurance cross country skiing tour demonstrated a decline in already low baseline CRP levels immediately after the tour and six weeks later. In a study of 200 obese individuals with impaired glucose tolerance randomised to a counselling session at their health care centre or a one month stay at a wellness centre, we found decreased levels of CRP in subjects admitted to the wellness centre. The effect remained at one, but not after three years of follow-up. In a prospective, nested, case-referent study with 308 ischemic strokes, 61 intracerebral haemorrhages and 735 matched referents, CRP was associated with ischemic stroke in both uni- and multivariate analyses. No association was found with intracerebral haemorrhages. When classifying ischemic stroke according to TOAST criteria, CRP was associated with small vessel disease. The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP, but neither with ischemic stroke nor with intracerebral haemorrhage. A study on 129 patients with atrial fibrillation was used to evaluate whether inflammation sensitive fibrinolytic variables adjusted for CRP could predict recurrence of atrial fibrillation after electrical cardioversion. In multivariate iv models, lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP and markers of the metabolic syndrome. In conclusion, lifestyle intervention can be used to reduce CRP levels, but it remains a challenge to maintain this effect. CRP is a marker of ischemic stroke, but there are no significant associations between the CRP1444 polymorphism and any stroke subtype, suggesting that the CRP relationship with ischemic stroke is not causal. The fibrinolytic variable, PAI-1, is associated with the risk of recurrence of atrial fibrillation after electrical cardioversion after adjustment for CRP. Our findings suggest a pathophysiological link between atrial fibrillation and PAI-1, but the relation to inflammation remains unclear.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Η χολοπαγκρεατική εκτροπή αποτελεί την πιο αποτελεσματική μέθοδο της βαριατρικής χειρουργικής όσο αφορά την απώλεια του βάρους και την υποχώρηση του σακχαρώδους διαβήτη τύπου 2, συνοδεύεται όμως συχνά από σημαντική έλλειψη θρεπτικών συστατικών. Η επιμήκης γαστρεκτομή είναι μια σχετικά νέα επέμβαση, η οποία σύμφωνα με μελέτες προκαλεί σημαντικού βαθμού απώλεια βάρους και υποχώρηση του σακχαρώδους διαβήτη τύπου 2. Σκοπός: Η προοπτική εκτίμηση και σύγκριση της επίδρασης της χολοπαγκρεατικής εκτροπής μακρών ελίκων και της λαπαροσκοπικής επιμήκους γαστρεκτομής στην υποχώρηση του σακχαρώδους διαβήτη τύπου 2, της υπέρτασης και της δυσλιπιδαιμίας, καθώς επίσης και στα επίπεδα ινσουλίνης, γλυκαγόνης, γκρελίνης, PYY και GLP-1( σε νηστεία αλλά και μετά από τη λήψη γλυκόζης ) σε ασθενείς με κλινικά σοβαρή παχυσαρκία και σακχαρώδη διαβήτη τύπου2. Μέθοδος: Δώδεκα ασθενείς (ΔΜΣ 57.6±9.9 kg/m2) υποβλήθηκαν σε χολοπαγκρεατική εκτροπή μακρών ελίκων και δώδεκα (ΔΜΣ 43.7±2.1 kg/m2 ) σε λαπαροσκοπική επιμήκη γαστρεκτομή. Όλοι οι ασθενείς παρουσίαζαν σακχαρώδη διαβήτη τύπου 2 και μελετήθηκαν προεγχειρητικά και σε 1, 3 και 12 μήνες μετά το χειρουργείο. Σε όλους τους χρόνους υποβλήθηκαν σε από του στόματος δοκιμασία ανοχής γλυκόζης. Αποτελέσματα: Το σωματικό βάρος σημείωσε σημαντική και αναλόγου μεγέθους μείωση και στις δύο ομάδες (Ρ<0.001). Στους 12 μήνες η ποσοστιαία απώλεια του υπερβάλλοντος σωματικού βάρους ήταν παρόμοια στις δύο ομάδες (Ρ=0.8) και ο σακχαρώδης διαβήτης είχε υποχωρήσει σε όλους τους ασθενείς. Η γλυκόζη, η ινσουλίνη και η αντίσταση στη δράση της παρουσίαζαν σημαντική μείωση έπειτα και από τις δύο επεμβάσεις, όμως η ευαισθησία στην ινσουλίνη ενισχύθηκε περισσότερο έπειτα από τη χολοπαγκρεατική εκτροπή (Ρ=0.003). Η αρτηριακή πίεση, η ολική και η LDL χοληστερόλη μειώθηκαν σημαντικά έπειτα από τη χολοπαγκρεατική εκτροπή (Ρ<0.001), όχι όμως και μετά την επιμήκη γαστρεκτομή. Τα τριγλυκερίδια μειώθηκαν σημαντικά και στις δύο ομάδες, ενώ η HDL χοληστερόλη παρουσίασε σημαντική αύξηση μόνο μετά την επιμήκη γαστρεκτομή (Ρ<0.001). Τα επίπεδα γκρελίνης νηστείας δεν μεταβλήθηκαν σημαντικά μετά τη χολοπαγκρεατική εκτροπή (Ρ=0.2), ενώ σημείωσαν σημαντική μείωση μετά την επιμήκη γαστρεκτομή (Ρ<0.001). Η απόκριση των ΡΥΥ και GLP-1 ενισχύθηκε σημαντικά και στις δύο ομάδες ασθενών (Ρ=0.001). Συμπεράσματα: Η λαπαροσκοπική επιμήκης γαστρεκτομή οδήγησε σε αναλόγου βαθμού απώλεια σωματικού βάρους και υποχώρηση του σακχαρώδη διαβήτη τύπου 2 με τη χολοπαγκρεατική εκτροπή μακρών ελίκων. Η χολοπαγκρεατική εκτροπή όμως ήταν περισσότερο αποτελεσματική όσο αφορά τη βελτίωση της ευαισθησίας στην ινσουλίνη, της δυσλιπιδαιμίας και της αρτηριακής υπέρτασης. / Biliopancreatic diversion (BPD) is the most effective bariatric procedure in terms of weight loss and remission of diabetes type 2 (DM2) but it is accompanied by nutrient deficiencies. Sleeve gastrectomy (SG) is a relatively new restrictive operation that has shown promising results concerning DM2 resolution and weight loss. Objective: To evaluate and compare prospectively the effects of BPD long limb (BPDLL) and SG on remission of DM2, hypertension and dyslipidemia and also on fasting, and glucose-stimulated insulin, glucose, glucagon, ghrelin, PYY and glucagon-like peptide-1 (GLP-1) levels in morbidly obese patients with DM2. Methods: Twelve patients (BMI 57.6±9.9 kg/m2) underwent BPDLL and 12 (BMI 43.7±2.1 kg/m2) underwent SG. All patients had DM2 and were evaluated before and 1, 3 and 12 months after surgery. Oral glucose tolerance test and blood sampling were carried out after an overnight fast and 30, 60 and 120 minutes after glucose ingestion. Results: Body weight decreased markedly in both groups (P<0.001); excess weight loss was similar in both groups at 12 months (P=0.08) and DM2 resolved in all patients. Glucose, insulin and insulin resistance decreased significantly after both procedures, but the BPDLL group had higher insulin sensitivity than the SG group at 1 year (P=0.003). Blood pressure, total and LDL cholesterol decreased markedly after BPDLL (P<0.001) but not after SG. Triglycerides decreased significantly after both operations but HDL increased significantly after SG only (p<0.001). Fasting ghrelin did not change significantly after BPDLL (P=0.2), but decreased markedly after SG (P<0.001). Fasting GLP-1 and PYY increased significantly after BPDLL only (P=0.01), however GLP-1 and PYY responses to glucose were significantly enhanced in both groups (P=0.001). Conclusion: SG results in weight loss and resolution of DM2 comparable to BPDLL, but BPDLL is more effective in terms of dyslipidemia resolution and blood pressure reduction.

Na última década, surgiram evidências de que a Síndrome Metabólica (SM), relatada de forma crescente entre adolescentes, tem início na vida intrauterina e seus sinais e sintomas já estão presentes na adolescência, porém, ainda faltam critérios diagnósticos específicos para essa faixa etária. O ciclo menstrual representa o resultado do funcionamento normal não apenas do eixo Hipotálamo-Hipófise-Ovário (HHO), do útero e do aparelho genital, mas também, do equilíbrio metabólico do organismo. Alterações no ciclo menstrual podem representar sinais de desequilíbrio e anormalidade. A SM está também relacionada à Síndrome dos Ovários Policísticos (SOP), disfunção ovariana caracterizada por oligoanovulação, hiperandrogenismo e/ou ovários policísticos. A resistência à insulina (RI) tem um papel central na fisiopatologia e na inter-relação dos componentes tanto da SM como também da SOP. A RI é compensada pelo aumento da produção de insulina pelas células beta pancreáticas, e essa hiperinsulinemia compensatória tem conseqüências no endotélio, nos fatores inflamatórios, no metabolismo glicídico e lipídico, além de afetar o ciclo menstrual pelo estímulo da androgênese ovariana, suprimindo a SHBG e possivelmente alterando o padrão da secreção pulsátil do GnRH. Estas alterações menstruais podem apresentar-se de forma precoce, antes das alterações metabólicas da RI, portanto, a avaliação atenta do padrão menstrual de adolescentes pode representar um valioso sinal que alerta para o risco metabólico e cardiovascular. Avaliamos o comportamento de parâmetros da Síndrome Metabólica e sua relação com o ciclo menstrual em adolescentes através de um estudo observacional transversal com 59 adolescentes do sexo feminino entre 12 e 19 anos e presença de pelo menos um dos seguintes fatores de risco para SM: Sobrepeso - Obesidade - Acantose Nigricans. Todas as adolescentes foram submetidas a uma avaliação clínica com levantamento de dados antropométricos, e laboratoriais composta de: Glicose de Jejum, Colesterol Total, HDL-Colesterol, Triglicerídeos, Teste Oral de Tolerância a Glicose (Glicose 120), Insulina pré (insulina jejum), pós TOTG (insulina 120), Folículo-Estimulante (FSH), Hormônio Luteinizante (LH), Testosterona Total (TT), Androstenediona, Foram criados 2 grupos:G-1- adolescentes com ciclos irregulares, e G-2- adolescentes com ciclos regulares. Das 59 adolescentes avaliadas, 36 formaram o G-1, e 23 o G-2. A média da idade ginecológica foi de 4,5 anos e da menarca 11,3 anos. Na análise estatística das diferenças nas variáveis clínicas e laboratoriais entre os grupos, observou-se que o G-1 apresentou: Cintura (p=0,026), Insulina de jejum (p=0,001), Glicose 120 (p=0,002), insulina 120 (p=0,0001), HOMA-IR (p=0,0008), Triglicerídeos (p=0,013), SM (p<0,0001) e SOP (p<0,0001) significativamente maiores e QUICK (p=0,008), G/I (p=0,002), HDL (p=0,001) significativamente menores que o G-2. (88,8% das adolescentes com ciclos irregulares no ultimo ano apresentavam irregularidade desde a menarca. Estes resultados demonstram uma associação significativa entre a irregularidade menstrual, RI, SM e SOP na população estudada. Todas as adolescentes com diagnóstico de SM apresentavam irregularidade desde a menarca e destas, 93,5% tiveram o diagnóstico de SOP. O nosso estudo chama a atenção para o comportamento do ciclo menstrual na adolescência em relação aos riscos cardiovasculares e metabólicos, sinalizando assim que outros estudos precisam ser desenvolvidos nesta população. / Evidences have appeared throughout the last decade that the metabolic syndrome(MS) (increasingly reported among teens) begins in intra-uterine life and its signs and symptoms are already present in adolescence. Nevertheless, specific diagnostic criteria for this age group are missing. The menstrual cycle represents the result of the normal functioning not only of the hypothalamus-hypophysis-ovarian axis (HHO), the uterus, and the genital apparatus, but also of the metabolic balance of the body. Menstrual cycle alterations may represent signs of imbalance and abnormality. MS is also linked to premature pubarche due to premature adrenarche and polycystic ovary syndrome (PCOS) characterized by an ovarian dysfunction oligoanovulação, hyperandrogenism and/or polycystic ovaries Insulin resistance (IR) has a central role in the pathophysiology and interrelation of components of MS and also of PCOS. Insulin resistance is compensated by increased insulin production by pancreatic beta cells. The compensatory hyperinsulinemia has consequences in the endothelium, inflammatory factors, glucose and lipid metabolism and affect the menstrual cycle by stimulating ovarian androgen, suppressing SHBG and possibly altering the pattern of pulsatile secretion of GnRH. These menstrual changes may present themselves at an early stage, before the metabolic changes of IR, so the careful assessment of the menstrual patterns of adolescents may represent a valuable warning sign for cardiovascular and metabolic risk. Evaluate the behavior of parameters of metabolic syndrome and its relation to the menstrual cycle in adolescents. Observational, transversal-cut study with 59 female adolescents between 12 and 19 years of age, and the presence of at least one of the following risk factors for MS; 1- Overweight, Obesity and Acanthosis Nigricans. All the adolescents underwent a clinical evaluation, with gathering of anthropometric data, and laboratory evaluation composed of: evaluation of fasting glucose, total cholesterol, HDL-cholesterol, triglycerides, Oral Glucose Tolerance Test after 120 minutes (Glucose-120), insulin pre-(fasting insulin), insulin post-OGTT-120 (insulin 120), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Total Testosterone (TT), Androstenedione, Two groups were created. G-1 adolescents with irregular cycles G-2 with regular menstrual cycles. From the 59 adolescents evaluated, 36 formed G-1 and 23 formed G-2. The average gynecological age was 4,5 years, and of the menarche 11,3 years. In the statistical analysis of the differences in clinical and laboratory variables between the groups, it was observed that G-1 Waist(p=0,026),FastingInsulin(p=0,001),Glucose 120(p=0,002), Insulin 120 (p =0,0001), HOMA IR (p = 0,0008) , Triglyceride (p = 0,013), SM(p<0,0001) e SOP(p<0,001) significantly higher and QUICK (p=0,008),G/I (p=0,002) and HDL (p = 0,001) significantly lower than G-2. (88,8% of adolescents with irregular cycles in the past year showed irregularity since menarche). This study shows a significant association between menstrual irregularity, IR, MS and PCOS in this population. All adolescents diagnosed with MS had irregularity since menarche and of these 93.5% were diagnosed with PCOS.Our study draws attention to the behavior of the menstrual cycle in adolescence in relation to cardiovascular and metabolic risks, thus signaling that further studies need to be developed in this population.

Orientador: Roberto Carlos Burini / Resumo: O aumento da permeabilidade intestinal promove o influxo de toxinas bacterianas do lúmen intestinal para o interior do hospedeiro, desencadeando em resposta inflamatória de baixo grau, semelhante à observada na expansão do tecido adiposo e na etiologia das doenças crônicas. Foi realizado estudo transversal para identificar os determinantes das concentrações plasmáticas de proteína ligadora de lipopolissacarídeo (LBP) em mulheres adultas ingressantes em programa para mudança do estilo de vida. Foram avaliadas 74 mulheres com idade entre 35 a 67 anos, as quais foram submetidas à avaliação sociodemográfica e clínica, antropométrica, de composição corporal e consumo alimentar, coleta sanguínea e bioquímica padrão. Todas as análises foram efetuadas pelo programa estatístico SPSS versão 19.0, e o nível de significância adotado foi de 5%. Observou-se que as concentrações da LBP foram significativamente maiores em mulheres com excesso de peso e que este biomarcador apresentou correlações moderadas com a circunferência abdominal, a pressão arterial e com o índice de gordura hepática. Similarmente, notou-se que a ingestão de frutose e de gordura poli-insaturada, a pressão arterial diastólica, a transaminase glutâmico-pirúvica e o percentual de gordura corporal total, influenciaram os níveis plasmáticos da LBP de maneira independente das demais variáveis. Desta forma, o presente estudo demonstra que a LBP está relacionada a dois componentes da síndrome metabólica e ao acúmulo hepático d... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

No description available.

Introdução: A doença cardiovascular é a principal causa de morbidade e mortalidade em pacientes com síndrome metabólica ou diabetes mellitus tipo 2. Como a disfunção endotelial precede o desenvolvimento da doença cardiovascular, seria desejável identificar e tratar a disfunção endotelial antes que a aterosclerose se desenvolva. Hoje, existe evidência clara para sustentar o efeito protetor do exercício físico regular em pacientes com síndrome metabólica ou diabetes mellitus. O que está menos claro é a relação da intensidade de treinamento e melhora na função endotelial. Objetivo: Avaliar o efeito de um programa de exercício físico, de alta e baixa intensidade, na função endotelial de pacientes com Síndrome Metabólica ou Diabetes Mellitus Tipo 2. Métodos: Foram estudados 31 pacientes com diabetes melittus tipo 2 ou síndrome metabólica, de idade média (±DP) de 58±6 anos, randomizados para treinamento aeróbio de alta intensidade (AI: 75 a 85% freqüência cardíaca máxima, n = 10), treinamento aeróbio de baixa intensidade (BI: 50 a 60% freqüência cardíaca máxima, n = 10) e controle (n = 11). O treinamento foi realizado por 50 minutos, 4 vezes por semana. Antes e após 6 semanas de treinamento, os sujeitos realizaram teste de esforço e estudo da função endotelial, por ultra-som de alta resolução da artéria braquial, avaliados após hiperemia reativa (dependente do endotélio) e após administração de nitrato (independente do endotélio). Resultados: O programa de treinamento aeróbio de alta intensidade resultou em um maior aumento da capacidade funcional, avaliado pelo tempo máximo tolerado no teste de esforço (AI antes 9,39±1,22 minutos e depois 12,12±1,24 minutos; BI antes 8,84s±1,82 minutos e depois 10,41±1,99 minutos; Controle antes 9,36±.1,21minutos e depois 8,96±.1,35minutos; p < 0,05). A diferença no diâmetro do vaso após hiperemia foi significativamente maior para o grupo de alta intensidade (AI antes 4,28±.0,73mm e depois 5,62±.0,95mm; BI antes 4,24±.0,49mm e depois 5,01±.0,56mm; Controle antes 4,31±.0,37mm e depois 4,23±.0,23mm; p < 0,05). Após nitrato, não houve diferença significativa para nenhum dos grupos (AI antes 5,13±.1,17mm e depois 5,20±.1,10mm; BI antes 4,93±.0,88mm e depois 5,07±.0,70mm; Controle antes 4,96±.0,36mm e depois 4,62±.0,36mm; p = 0,565). Conclusões: Quando comparado ao treinamento aeróbio de baixa intensidade e controle, o treinamento aeróbio de alta intensidade melhorou a capacidade funcional e resposta vasodilatadora dependente do endotélio, em pacientes com síndrome metabólica ou diabetes mellitus tipo 2. Estes achados sugerem que o treinamento físico de alta intensidade possa ser considerado como alternativa preventiva nestes pacientes. / Introduction: Cardiovascular disease is the major cause of morbidity and mortality in patients with the metabolic syndrome or diabetes mellitus type 2. As the endothelial dysfunction precedes the development of cardiovascular disease, it would be desirable to identify and treat the endothelial dysfunction before the development of atherosclerosis. There is currently clear evidence to support the protective effect of regular physical exercise on patients with metabolic syndrome or diabetes mellitus. What is less clear is the relationship between training intensity and improvement in endothelial function. Objective: Evaluate effect of a physical exercise program, of high and low intensity, on endothelial function of patients with Metabolic Syndrome or Diabetes Mellitus Type 2. Methods: Thirty one patients with Diabetes Mellitus type 2 or metabolic syndrome were studied, with mean age (±SD) of 58±6 years, randomized for high intensity aerobic training (AI: 75-85% of maximum heart rate, n = 10), low intensity aerobic training (BI: 50-60% maximum heart rate, n = 10) and control (n = 11). The training was performed for 50 minutes, four times a week. Before and after 6 weeks of training, subjects performed the exercise testing and had been studied for endothelial function, by high resolution ultrasound of the brachial artery, assessed after reactive hyperemia (endothelium dependent) and after nitrate administration (endothelium independent). Results: The high intensity aerobic training resulted in a higher increase of the functional capacity, assessed by maximum tolerated time on the exercise testing (AI before 9.39±1.22 minutes and after 12.12±1.24 minutes; BI before 8.84s±1.82 minutes and after 10.41±1.99 minutes; Controls before 9.36±.1.21minutes and after 8.96±.1.35minutes; p < 0.05). The diameter difference of the vessel after hyperemia was significantly higher for the high intensity group (AI before 4.28±0.73mm and after 5.62±0.95mm; BI before 4.24±0.49mm and after 5.01±0.56mm; Controls before 4.31±0.37mm and after 4.23±.0.23mm; p < 0.05). After nitrate, there was no significant difference for none of the groups (AI before 5.13±.1.17mm and after 5.20±.1.10mm; BI before 4.93±.0.88mm and after 5.07±.0.70mm; Controls before 4.96±.0.36mm and after 4.62±.0.36mm; p = 0.565). Conclusions: When compared to the low intensity aerobic training and controls, the high intensity aerobic training improved the functional capacity and vasodilator response endothelium-dependent in patients with metabolic syndrome and diabetes mellitus type 2. These findings suggest that physical training of high intensity might be considered as a preventive alternative in those patients.

L'hypoxie intermittente (HI), induite par les apnées du sommeil, conduit à des altérations de la sensibilité à l'insuline et de l'homéostasie glucidique mais les mécanismes impliqués restent mal connus. L'objectif de ce travail était d'étudier les effets et les mécanismes sous jacents d'une exposition chronique à l'HI sur l'homéostasie glucidique. L'HI induit une résistance à l'insuline à la fois systémique et tissulaire, ainsi qu'une amélioration de la tolérance au glucose associée à une activation de l'AMPK musculaire. L'HI cause également des altérations du foie et du tissu adipeux associées à un changement du pattern d'expression des gènes dans ces tissus et à un risque accru de développement de pathologies vasculaires comme l'athérosclérose. Enfin, la délétion de PHD1, une des protéines régulatrices de HIF-1, entraîne une résistance à l'insuline associée une stéatose hépatique, faisant de HIF-1 une cible potentielle impliquée dans les altérations metaboliques induites par l'HI. / Intermittent hypoxia (IH), induced by sleep apnea, leads to alterations in insulin sensitivity and glucose homeostasis but the mechanisms involved remains poorly understood. The objective of this work was to study the effects and the underlying mechanisms of chronic exposure to IH on glucose homeostasis. IH induces both systemic and tissue-specific insulin resistance , as well as improved glucose tolerance associated with an activation of muscle AMPK. IH also causes a change in the pattern of gene expression in liver and adipose tissue and an increased risk of vascular pathologies such as atherosclerosis development. Finally, the deletion of PHD1, a regulatory protein of HIF-1, leads to insulin resistance associated with hepatic steatosis, making HIF-1 a possible target involved in the metabolic changes induced by IH.

Le syndrome métabolique comme le diabète de type 2 sont des pathologies chroniques souvent étroitement liées. Le syndrome métabolique via des dysfonctionnements physiologiques qui s'auto-entretiennent et s'amplifient conduira au diabète de type 2. Les dysfonctionnement majeurs sont l'obésité abdominale, l'inflammation et le stress oxydant tissulaire et enfin l'insulino-résistance des tissus sensibles à l'insuline. Il convient donc de lutter efficacement contre ces dysfonctionnements afin de lutter contre ces pathologies chroniques. Les travaux de l'équipe dans laquelle j'ai effectué ma thèse ont permis de mettre en évidence les effets pléiotropes de substances de la famille des dérivés caffeoyls. Ces dérivés largement reconnus comme substances antioxydantes ont des effets insulino-sensibilisants (augmentent le captage de glucose sous stimulus insulinique) et aussi insulino-stimulants (augmentent la capacité sécrétrice de la cellule -pancréatique). Les plantes qui produisent ces dérivés caffoyls sont donc des sources intéressantes de nouveaux aliments santé, d'allégations ou encore de boissons infusées aptes à lutter contre le syndrome métabolique. Les Astéracées semblent disposer de ces substances bénéfiques.Durant ma thèse, j'ai pu montré l'effet antidiabétique d'un extrait de racine de chicorée sauvage (NCRAE), riche en acide chicorique (CRA) et en dérivés caffeoyl-quinic acides (CQAs). L'analyse de l'extrait par LC-MS a permis de déterminer le ratio CRA/CQAs de 70/30. Nous avons montré qu'un mélange d'acide chicorique et d'acide chlorogénique (70/30) mime l' effet antidiabétique de NCRAE. Nous démontrons pour la première fois le bénéfice antidiabétique d'un mélange de dérivés caffeoylsDe nombreuses Astéracées produisent des mélanges divers de dérivés caffeoyls. Afin de mieux comprendre les effets de mélanges caffeoyls nous avons décidé de réaliser une évaluation des effets biologiques in vitro d'extraits riches en caffeoyls issus de dix Astéracées. Nous voulons ensuite réaliser une analyse corrélative entre leurs contenus et leurs effets. L'analyse LC-MS est en cours actuellement.Enfin, deux plantes exotiques (du Congo Kinshasa) bien connues pour leur vertu antidiabétique par les tradipraticiens ont été étudiées. Bien que faisant parties d'autres familles botaniques, celles-ci contiennent également des dérivés caffeoyls. Il était donc intéressant d'appliquer nos critères d'évaluation in vitro du potentiel antidiabétique d'une plante afin d'envisager ou non l'implication des dérivés caffeoyls.Mon travail soutien l'usage en mélanges des dérivés caffoyls afin de lutter contre le syndrome métabolique et le diabète de type 2. / Metabolic syndrome and type 2 diabetes are considered as chronic pathologies. The metabolic syndrome via physiological dysfunctions that self-sustain and expand will lead to type 2 diabetes. The major dysfunctions are abdominal obesity, inflammation and tissue oxidative stress and finally tissue insulin resistance. insulin sensitive. It is therefore necessary to fight effectively against these dysfunctions in order to fight against these chronic pathologies. The work of the team in which I carried out my thesis made it possible to highlight the pleiotropic effects of substances of the family of caffeoyls derivatives. These derivatives widely recognized as antioxidant substances have insulin-sensitizing effects (increase glucose uptake insulin stimulus) and also insulin-stimulating (increase the insulin secretion capacity of the -pancreatic cell). The plants that produce these caffoyl derivatives are therefore interesting sources of new health foods, claims or beverages infused to oppose the metabolic syndrome. Asteraceae seem to have these beneficial substances.During my thesis, I was able to show the antidiabetic effect of wild chicory root extract (NCRAE), rich in chicoric acid (CRA) and caffeoyl-quinic acid derivatives (CQAs). Analysis of the extract by LC-MS determined the CRA / CQAs ratio of 70/30. We have shown that a mixture of chicoric acid and chlorogenic acid (70/30) mimics the antidiabetic effect of NCRAE. We demonstrate for the first time the antidiabetic benefit of a mixture of caffeoyl derivativesMany Asteraceae produce various mixtures of caffeoyl derivatives. In order to better understand the effects of caffeoyl mixtures, we decided to carry out an evaluation of the in vitro biological effects of caffeoyl rich extracts from ten Asteraceae. We then want to carry out a correlative analysis between their contents and their effects. LC-MS analysis is ongoing.Finally, two exotic plants (Congo Kinshasa) well known for their antidiabetic properties by traditional "healers" were studied. Although belonging to other botanical families, these also contain caffeoyl derivatives. It was therefore interesting to apply our criteria of in vitro evaluation of the antidiabetic potential of a plant in order to envisage or not the implication of the caffeoyls derivatives.My work supports the use in mixtures of caffoyl derivatives to fight against metabolic syndrome and type 2 diabetes.