Raw seeds of sixteen common bean (Phaseolus vulgaris L.) cultivars were evaluated along two consecutive harvests (2001/2002 and 2002/2003) concerning their physicochemical characteristics, as well as the effect of cooking and storage conditions on starch and dietary fiber contents. Serum lipids and blood glucose levels were also evaluated in normolipidemic-normoglycemic rats witch were fed diets containing bean cultivars with different soluble fiber/total fiber ratios (SF/TF): Pérola diet (0.11), Diamante Negro diet (0.19) and Iraí diet (0.26); control group was fed a standard diet (with insoluble fiber). Except for dry matter, moisture, and total dietary fiber, cultivars kept their chemical characteristics between harvests. Regarding similarity among macronutrient levels (crude protein-CP, total dietary fiber, insoluble dietary fiber, soluble dietary fiber-SF, digestible starch-DS, and resistant starch-RS) seeds from harvests 2001/2002 and 2002/2003 were categorized into four different groups; the same was done for micronutrients (Fe, Zn, Mn, Cu, Ca, Mg, and P), and four groups were also identified. Guateian 6662 and Rio Tibagi were considered the cultivars with the best nutritional profile (highest levels of CP, SF, DS, Fe, and Zn). Storage under refrigerated or freezing conditions did not change fiber content of cooked beans, but decreased their DS content and increased RS content, mainly in seeds with low RS levels before cooking. Concerning biological response, rats fed bean diets experienced lower values for serum cholesterol (P<0.05) and lower glycemic indexes (P<0.05). It was also observed a similar weight gain among groups, however animals fed bean based diets showed lower fat retention (P<0.05). The effects of bean diets on experimental groups were more remarkable in animals fed Iraí diet (SF/TF: 0.26). / Foram analisadas as características físico-químicas de sementes cruas de dezesseis cultivares de feijão comum (Phaseolus vulgaris L.), ao longo de duas safras consecutivas (2001/2002 e 2002/2003), bem como os teores de amido e fibra alimentar nas sementes após cozimento e estocagem. Avaliaram-se, também, os lipídeos séricos e a glicose sanguínea de ratos normolipidêmicos e normoglicêmicos, alimentados com dietas contendo cultivares de feijão com diferentes relações fibra solúvel/fibra total (FS/FT): dieta Pérola (0,11), dieta Diamante Negro (0,19) e dieta Iraí (0,26); o grupo controle recebeu dieta padrão (com fibra insolúvel). Exceto pelos teores de matéria seca, umidade e fibra alimentar total, as cultivares estudadas mantiveram suas características físico-químicas constantes ao longo das safras. Conforme a similaridade nos teores de macronutrientes (proteína bruta-PB, fibra alimentar total, fibra alimentar insolúvel, fibra alimentar solúvel-FS, amido disponível-AD e amido resistente-AR) as sementes das safras 2001/2002 e 2002/2003 foram categorizadas em quatro grupos distintos; da mesma forma, em relação aos micronutrientes (Fe, Zn, Mn, Cu, Ca, Mg e P), quatro grupos puderam ser identificados. As cultivares Guateian 6662 e Rio Tibagi apresentaram o melhor perfil nutricional (maiores teores de PB, FS, AD, Fe e Zn). A armazenagem sob refrigeração e o congelamento não determinaram alterações nos teores de fibra dos grãos cozidos, mas redução do AD e aumento do AR, principalmente naqueles com AR mais baixo antes do cozimento. Em relação à resposta biológica, os ratos alimentados com dietas contendo feijão apresentaram valores para colesterol sérico e índice glicêmico menores que os do grupo controle (p<0,05). Foi observado, também, que apesar do ganho de peso dos animais ter sido semelhante entre os grupos, os ratos alimentados com as dietas contendo feijão apresentaram menor retenção de gordura corporal (p<0,05). Os efeitos das dietas sobre os animais experimentais foram mais expressivos no grupo alimentado com a dieta Iraí (FS/FT: 0,26).

Submitted by Livia Mello (liviacmello@yahoo.com.br) on 2016-10-10T14:37:56Z No. of bitstreams: 1 TeseDB.pdf: 11488073 bytes, checksum: e161623d5cf03f13400ba78b788a3243 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-20T19:56:02Z (GMT) No. of bitstreams: 1 TeseDB.pdf: 11488073 bytes, checksum: e161623d5cf03f13400ba78b788a3243 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-20T19:56:09Z (GMT) No. of bitstreams: 1 TeseDB.pdf: 11488073 bytes, checksum: e161623d5cf03f13400ba78b788a3243 (MD5) / Made available in DSpace on 2016-10-20T19:56:15Z (GMT). No. of bitstreams: 1 TeseDB.pdf: 11488073 bytes, checksum: e161623d5cf03f13400ba78b788a3243 (MD5) Previous issue date: 2016-03-22 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / The thesis consists of three studies described below. Study I, entitled: Poor glycemic control impacts the linear dynamic and nonlinear heart rate in type 2 diabetes mellitus (T2DM) whose objective was to evaluate the relationship between glycemic control and cardiac autonomic modulation in patients with T2DM without autonomic neuropathy cardiovascular. This is a descriptive, prospective and cross-sectional study. The resting heart rate (HR) and RR interval (RR intervals) were obtained and calculated by linear methods and nonlinear heart rate variability (HRV). Insulin, HOMA-IR, fasting glucose and HbA1c were obtained by blood tests. We concluded that the poor glycemic control associated with cardiac autonomic modulation indices in patients with type 2 diabetes, though not exhibit cardiovascular autonomic neuropathy. Following the Study II, entitled Type 2 diabetes coexistence of effects and systemic hypertension (SH) in HRV and cardiorespiratory performance, which aimed to evaluate the influence of hypertension in cardiac autonomic neuropathy and cardiorespiratory fitness in subjects with diabetes mellitus type 2. The evaluation included collection of iRR for further analysis of HRV, it was collected in the supine position followed by incremental cardiopulmonary exercise test (ICET) on a cycle ergometer. The results revealed a greater loss of HRV when there is overlapping of diseases. Additionally, there was an association of responses affected HRV with cardiopulmonary function markers impaired to exercise. Finally, the Study III, entitled: Potential effects on cardiorespiratory and metabolic status after a physical aerobic concurrent training program and has resisted in diabetic volunteers - Randomized Study and controlled. The objective was to evaluate metabolic profile, glycemic control and exercise capacity in diabetic volunteers after participating in an aerobic and resistance concurrent training program (AR-CT) for a period of three months. The evaluation included the ICET the cycle ergometer and 1-RM tests. Ventilation, hemodynamic measurements were performed during the ICET and peripheral muscle strength by isokinetic dynamometer. The program consisted of 30 minutes of aerobic exercise and 30 minutes of resistance exercise of upper and lower limbs. The results showed an improvement in glycemic control and lipid profile in addition to increased peripheral muscle strength and exercise capacity. These data together suggest that the exercise program constitutes an important strategy in the treatment of type 2 diabetes, producing both physiological and functional improvements in this population. / A tese constou de três estudos descritos a seguir. O Estudo I, intitulado: Pobre controle glicêmico impacta a dinâmica linear e não-linear da frequência cardíaca no diabetes mellitus tipo 2 (DM2), cujo objetivo foi avaliar a relação entre controle glicêmico e modulação autonômica cardíaca em indivíduos com DM2 sem neuropatia autonômica cardiovascular. Trata-se de um estudo descritivo, prospectivo e transversal. A frequência cardíaca de repouso (FC) e intervalo RR (iRR) foram obtidos e calculados por métodos lineares e não-lineares de variabilidade de frequência cardíaca (VFC). Insulina, HOMA-IR, glicemia de jejum e HbA1c foram obtidas por análises sanguíneas. Concluímos que o controle glicêmico deficiente relaciona-se com índices de modulação autonômica cardíaca em indivíduos com DM2, ainda que não apresentem neuropatia autonômica cardiovascular. Na sequência, o Estudo II, intitulado: Efeitos da coexistência da diabetes tipo 2 e da hipertensão arterial sistêmica (HAS) na VFC e no desempenho cardiorrespiratório, que objetivou avaliar a influência da HAS na modulação autonômica cardíaca e aptidão cardiorrespiratória de sujeitos com diabetes mellitus tipo 2. A avaliação incluiu coleta de dos iRR, para posterior análise da VFC, a mesma foi coletada na posição supina seguida de teste de exercício cardiopulmonar incremental (TECI) no cicloergômetro. Os resultados revelaram um maior prejuízo da VFC quando há sobreposição das doenças. Adicionalmente, houve associação das respostas prejudicadas da VFC com marcadores de função cardiopulmonar prejudicada ao exercício. Finalmente, o Estudo III, intitulado: Potenciais efeitos no status cardiorrespiratório e metabólico após um programa de treinamento físico concorrente aeróbio e resistido em diabéticos – Estudo Randomizado e Controlado. O objetivo foi avaliar perfil metabólico, controle glicêmico e capacidade de exercício em voluntários diabéticos após participarem de um programa de treinamento concorrente aeróbio e resistido (TC-AR) por um período de 3 meses. A avaliação incluiu o TECI no cicloergômetro, exames laboratoriais, teste isocinético e teste de 1-RM. Foram realizadas medidas ventilatórias, hemodinâmicas durante o TECI bem como da força muscular periférica por meio da dinamometria isocinética. O programa foi constituído por 30 minutos de exercícios aeróbios e 30 minutos de exercícios resistidos de membros superiores e inferiores. Os resultados mostraram melhora do controle glicêmico e do perfil lipídico, além de aumento da força muscular periférica e da capacidade de exercício. Esses dados juntos sugerem que o programa de exercícios constitui-se uma importante estratégia no tratamento de DM2, produzindo melhoras tanto fisiológicas como funcionais nessa população.

A hipertensão é uma das principais causas de morbidade e mortalidade no Brasil. Os hipertensos muitas vezes apresentam perfil lipídico e glicidico desfavoráveis. A alimentação pode desempenhar um papel importante na redução da pressão arterial (PA) e no perfil lipídico e controle glicêmico desses pacientes. Avaliar o impacto de uma intervenção nutricional adaptada ao padrão alimentar brasileiro no controle dos níveis pressóricos e metabólico de pacientes hipertensos em acompanhamento em um serviço de atenção primária de saúde do município de São Luís do Maranhão. Metodologia: ensaio clínico randomizado utilizando uma dieta de baixo índice glicêmico combinada ao aumento do consumo de frutas, vegetais, grãos integrais e laticínios desnatados que são os princípios do Dietary Approach to Stop Hypertension (dieta DASH). Foram alocados randomicamente 206 pacientes hipertensos que foram acompanhados por 6 meses. O grupo controle (GC, n=101) recebeu aconselhamento padrão, focado na redução da ingestão de sal. Resultados: Dos 206 pacientes randomizados, 156 (37 homens, 119 mulheres) completaram o estudo. A idade média dos participantes foi de 60,1 (DP 12,9) anos. Após 6 meses, houve redução na média da pressão arterial sistólica (PAS) em 14,4 mmHg e na diastólica (PAD) de 9,7 mmHg no grupo experimental (GE), em comparação a 6,7 mmHg e 4,6 mmHg, respectivamente, no GC. Após o ajuste para mudança de peso corporal, PA na linha de base e idade, essas diferenças entre os grupos foram de aproximadamente 9,2 mmHg e 6,2 mmHg, respectivamente. Ocorreram tambem variações estatisticamente significantes na excreção urinária de sódio, reduzida em 43,4 mEq/24 h no GE, bem como o colesterol total (-46.6mg/dl) , LDL colesterol (-42.5mg/dl), triglicérides (-31.3mg/dl), glicemia de jejum (-9.6mg/dl ) e hemoglobina glicada (-0,1%). O consumo alimentar modificou-se no GE com aumento do consumo de vegetais, passando de 2,97 para 5,85 ; frutas (4,09-7,18); feijão (1,94-3,13) e peixes (1,80 para 2,74). Modificações importantes relacionadas à redução significativa de carboidratos, teor lipídico e carga glicêmica da dieta, foram observadas. Conclusão: Este estudo mostrou a viabilidade e a eficácia de uma abordagem dietética com base no padrão alimentar brasileiro, na redução da PA e parâmetros bioquímicos inadequados, podendo causar um grande impacto na saúde pública. / Hypertension is one of the leading causes of morbidity and mortality in Brazil. Hypertensive patients often have unfavorable lipid profile and glucose level. Nutrition may play an important role in reducing blood pressure (BP) and metabolic control of these patients. Objective: To evaluate the impact of nutritional intervention adapted to the Brazilian food in controlling blood pressure and metabolic monitoring in hypertensive patients from a primary care service in São Luís do Maranhão. Methodology: Randomized clinical trial using a low-glycemic index diet combined with increased consumption of fruits, vegetables, whole grains and nonfat dairy products which principles of the Dietary Approach to Stop Hypertension (DASH). We randomly assigned 206 patients with hypertension who were followed for 6 months. The control group (CG, n = 101) received standard counseling, focused on reducing salt intake. Results: Of the 206 patients randomized, 156 (37 men, 119 women) completed the study. The average age of participants was 60.1 (SD 12.9) years. After 6 months, a reduction in mean systolic blood pressure (SBP) by 14.4 mmHg and diastolic blood pressure (DBP) by 9.7 mmHg in the experimental group (EG), compared to 6.7 mmHg and 4.6 mmHg, respectively GC. After adjusting for change in body weight at baseline BP and age, these differences between groups were approximately 9,2 mmHg and 6,2 mmHg, respectively. There were also statistically significant variability in urinary sodium excretion, reduced by 43.4 mEq/24 h at GE, as well as total cholesterol (-46.6mg/dl), LDL cholesterol (-42.5mg/dl), triglycerides (-31.3 mg / dl), fasting glucose (-9.6mg/dl) and glycated hemoglobin (-0.1%). The EG increased the intake of vegetables, from 2.97 to 5.85; fruits (4,09 to 7.18), beans (1.94 to 3.13) and fish (1.80 to 2.74).Significant changes related to the significant reduction of carbohydrate, lipid content and glycemic load of the diet have been observed. Conclusion: This study showed the feasibility and effectiveness of a dietary approach based no Brazilian pattern in reducing blood pressure and biochemical parameters. Dietary changes as proposed may have a great impact on public health.

A cada dia cresce o interesse por alimentos ricos em carboidratos não disponíveis em virtude da relação inversa entre seu consumo e o risco de doenças crônicas não transmissíveis (DCNT). No presente trabalho, foi avaliado o potencial fisiológico da farinha de banana verde (FBV) como ingrediente funcional. Em ratos adultos, foi realizado ensaio de média duração (28 dias) para avaliação do efeito trófico da FBV sobre o intestino grosso e de parâmetros relacionados à tolerância à glicose. Em humanos, foram realizados ensaios clínicos de curta e média duração para avaliação dos efeitos sobre resposta glicêmica; liberação de hormônios gastrintestinais relacionados à saciedade; status antioxidante; fome e saciedade; e funcionamento intestinal. A FBV foi produzida com banana verde, Musa acuminata, de acordo com patente depositada pelo grupo (Patente (RPI - 1941), 2008). A FBV é uma fonte concentrada de carboidratos não disponíveis, com 56% de AR e 8% de FAT na base integral. A adição de FBV nas rações provocou efeito trófico no ceco dos animais, evidenciado por aumento no índice metafásico, número de células da cripta e profundidade das criptas. Além disso, a ração com FBV proporcionou melhora nos parâmetros relacionados à tolerância à glicose. Em voluntários saudáveis, a ingestão de uma única refeição adicionada de 8 g de FBV proporcionou aumento na saciedade e boa correlação entre os parâmetros fome/saciedade e níveis plasmáticos de grelina e insulina, melhorou o funcionamento intestinal, além de resultar em alta fermentabilidade in vitro em relação à lactulose. Após ingestão diária da FBV por 14 dias, os resultados da ingestão de RC0 (refeição controle antes do tratamento) e de RC14 (RC0 após 14 dias de tratamento) mostraram que ocorre melhora na tolerância à glicose, evidenciada pela menor liberação de insulina durante o GTT. O efeito positivo sobre funcionamento intestinal, sobre saciedade e sobre liberação de hormônios gastrintestinais no plasma permaneceu após ingestão prolongada da FBV. A adição da FBV na refeição resultou em aumento da capacidade antioxidante in vitro. A FBV apresenta inúmeros atributos positivos para elaboração de produtos que ampliem as opções para uma alimentação saudável, bem como propiciem saúde intestinal, visando a diminuição do risco de DCNT. / The study of unavailable carbohydrates has been of great concern due to their inverse relation with the risk for non-transmissible chronic diseases (NTCD). In the present study, the functional potential of unripe banana flour (UBF) was evaluated. In rats, a medium-term assay was carried in order to evaluate parameters related to glucose tolerance and the trophic effect of UBF on the large bowel. In healthy volunteers, short and medium-term clinical assays were carried to evaluate the effects of UBF on glycemic response; release of gastrointestinal hormones related to satiety (ghrelin, leptin and insulin); antioxidant status; hunger and satiety; and intestinal health. UBF was produced with unripe banana, Musa acuminata, subgroup Cavendish, maturation stage I, in industrial scale and according to a patent deposited by the group (Patent (RPI - 1941), 2008). UBF is a concentrated source of unavailable carbohydrates, with 56% RS and 8% DF (wet weight). Adding UBF in rat rations resulted in a trophic effect in the animals\' cecum, which was evidenced by increase in the metaphasic index, number of crypt cells and crypt depth. Moreover, the ration with UBF resulted in better glucose tolerance parameters. In healthy volunteers, adding UBF (8 g) to an only meal provided significant satiety and good correlation between the parameters hunger/ satiety and plasmatic levels of ghrelin and insulin, improved bowel habit, as well as resulted in high in vitro fermentability in relation to lactulose. After daily intake of UBF for 14 days, the results of the intake of RC0 (control meal before treatment) and RC14 (RC0 after 14 days treatment) showed that there is a positive post-prandial variation in the plasmatic concentrations of gastrointestinal hormones, as well as improvement in glucose tolerance, evidenced by lower insulin release during GTT. The positive effect on bowel habit, satiety and release of gastrointestinal hormones in plasma was kept after prolonged intake of UBF. Adding UBF to the meal provided significant increase in the in vitro antioxidant capacity. UBF presents several positive attributes for the elaboration of products that may increase the options for healthy eating habits, as well as provide intestinal health, always aiming to decrease the risk for NTCD.

L’objectif général de ce travail était d’évaluer l’effet du diabète de Type 1 et de l’hyperglycémie chronique (reflétée par un niveau élevé d’HbA1c), chez des patients indemnes de complications micro et macrovasculaires, sur la disponibilité en oxygène (O2) au niveau musculaire et cortical et ses répercussions sur l’aptitude physique aérobie. Dans un premier temps, nous nous sommes attardés à étudier l’effet du diabète et des niveaux élevés d’HbA1c sur les différentes étapes de la cascade d’oxygène (à savoir la diffusion alvéolo-capillaire, le transport artériel et la libération de l’O2 au niveau musculaire) ainsi que sur l’oxygénation musculaire estimée par la Spectroscopie dans le proche Infra-Rouge (NIRS) durant un exercice incrémental et voir les répercussions possibles sur la consommation maximale d’oxygène (&#12310;V &#775;O&#12311;_2max). Nous avons montré que les patients DT1 présentent une capacité de diffusion alvéolo-capillaire ainsi qu’une capacité de transport artériel d’O2 comparable aux sujets sains. En revanche, les patients ayant un niveau élevé d’HbA1c présentent une altération de &#12310;V &#775;O&#12311;_2max ainsi qu’une réduction du volume sanguin musculaire (reflétée par une baisse de l’hémoglobine totale) et une nette baisse de la déoxyhémoglobine (HHb) au niveau du muscle actif aux intensités proches de l’exercice maximal. Ce dernier résultat pourrait s’expliquer par l’affinité plus importante de HbA1c pour l’O2 et/ou une altération de la redistribution de débit sanguin entre les vaisseaux nutritifs et non nutritifs. L’altération du volume sanguin au niveau musculaire chez les patients présentant un mauvais contrôle glycémique peut prévenir les cliniciens du dysfonctionnement de la microcirculation survenant avant même qu’une microangiopathie se manifeste à l’état clinique (Étude 1). Dans un second temps, nous nous sommes intéressés à la fonction cérébrale. Notre objectif étant d’évaluer l’hémodynamique cérébrale durant un exercice incrémental maximal. Nous avons trouvé une altération de l’hémodynamique cérébrale (baisse de l’hémoglobine totale) aux intensités proches de l’exercice maximal chez les patients DT1 qui présentent un mauvais contrôle glycémique (Étude 2). Ces deux travaux nous montrent bien que les sujets diabétiques de type 1 indemnes des complications micro et/ou marcovasculaires présentent une faible aptitude physique aérobie qui peut s’expliquer à la fois par une altération de l’oxygénation musculaire et cérébrale. Ces études mettent également en évidence l’intérêt d’associer la NIRS avec un exercice maximal. Ce dernier place les tissus en situation de besoin maximal en O2 ce qui permet de mettre en exergue des altérations fonctionnelles de la microcirculation avant même l’apparition de complications microvasculaires détectables par les tests cliniques habituels. / This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence oxygen supply including alveolar capillary diffusion, oxygen delivery and release, to active muscle and prefrontal cortex during maximal exercise. We first studied the effect of high level of HbA1c on oxyhemoglobin dissociation at the active muscle measured by Near Infra-Red Spectroscopy (NIRS) during maximal exercise. We found that alveolar capillary diffusion and arterial oxygen content was comparable between patients with type 1 diabetes and healthy subjects. However, patients with inadequate glycemic control but without any clinically detectable vascular complications displayed an impaired aerobic capacity as well as a reduction in blood volume and a dramatic impairment in deoxyhemoglobin (HHb) increase in active skeletal muscle during intense exercise. The latter supports the hypotheses of an increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy (Study 1). Secondly, we aimed at investigating prefrontal cortex hemodynamic during an incremental maximal exercise in patients with uncomplicated type 1 diabetes, taking into account chronic glycemic control. We observed that levels and changes in regional cerebral blood volume – as reflected by change in total hemoglobin – were lower at high intensities of exercise in patients with inadequate glycemic control (Study 2).In summary, the physiological stimulus of maximal exercise coupled with NIRS measurement highlighted subclinical disorders of both cerebral hemodynamic and muscle oxygenation in poorly-controlled patients with type 1 diabetes albeit free from any clinical microangiopathy.

L’activité physique (AP) est liée à plusieurs bénéfices pour la santé chez les personnes atteintes de diabète de type 1 (DT1), mais elles sont peu actives dû à la peur des hypoglycémies liée à l’AP. Un apport en glucides est souvent requis pour prévenir les hypoglycémies lors d’une AP, mais il y a un manque de connaissances quant à la quantité à consommer et la distribution temporelle idéales des glucides. Notre objectif est de comparer l’efficacité de 2 stratégies de collation pour maintenir la glycémie dans les cibles (4,0 - 10,0 mmol/L) lors d’une AP chez les adolescents et adultes avec le DT1. Les participants (N=33) ont effectué 2 interventions durant lesquelles une heure d’ergocycle à intensité moyenne a été réalisée. Ils consommaient un apport en glucides de 0,5g/kg du poids corporel et cet apport était aléatoirement consommé en une prise unique (PU) avant l’AP ou en une prise répartie (PR) avant et pendant l’AP. La GC était mesurée toutes les 10 minutes durant l’AP. Quatre participants ont eu une hypoglycémie durant l’AP avec la PU comparativement à 6 participants pour la PR (P=0,42). Il n’y avait pas de différence significative pour le pourcentage de temps passé dans les cibles entre les deux stratégies (PU : 75 ± 35%; PR : 87 ± 26%; P=0,12). Nos résultats suggèrent qu’un apport en glucide de 0.5g/kg du poids corporel est une option raisonnable pour une AP d’intensité moyenne d’une heure. Les deux stratégies sont similaires pour prévenir les hypoglycémies lors de l’AP. / Physical activity (PA) is associated to many health benefits in people living with type 1 diabetes (T1D), but these patients are not very active due to the fear of PA-related hypoglycemia. Carbohydrate intake is often required to prevent hypoglycemia during PA, but there is a lack of knowledge about the ideal amount to consume and the timing distribution of carbohydrates. Our objective is to compare the efficacy of two snack strategies to maintain glucose levels in the target range (4.0 – 10.0 mmol/L) during PA in adolescents and adults living with T1D. The participants (N = 33) took part in 2 interventions during which one hour of moderate intensity ergocycle was performed. They consumed a carbohydrate intake of 0.5g/kg of body weight and this intake was randomly consumed in a single intake (SI) before PA or in a distributed intake (DI) before and during PA. Capillary blood glucose was measured every 10 minutes during PA. Hypoglycemia occurred in 4 participants with SI compared to 6 participants for DI (P = 0.42). There was no significant difference in the percentage of time spent in the target range between the two strategies (SCI: 75 ± 35%; DCI: 87 ± 26%; P = 0.12). Our results suggest that a carbohydrate intake of 0.5g/kg of body weight is a reasonable option for one hour of moderate PA. The two snack strategies are similar to prevent hypoglycemia during PA.

Le diabète de type 1 (DT1) se caractérise par la destruction auto-immune des cellules ß des îlots de Langerhans du pancréas productrices d’insuline, entraînant un état d’hyperglycémie chronique. Malgré une prise en charge très fine de la maladie, s’appuyant sur l’insulinothérapie fonctionnelle, les personnes vivant avec le DT1 sont fréquemment sujettes à des épisodes hypoglycémiques et hyperglycémiques en raison de difficultés à adapter le traitement insulinique, notamment lors de l’activité physique. L’activité physique procure de nombreux bénéfices pour la santé que l’on ait ou non un diabète. Cependant, dans le cadre du DT1, les excursions glycémiques lors de l’activité physique peuvent conduire à des barrières à l’activité physique dans cette population ou peuvent limiter les performances sportives d’athlètes vivant avec le DT1. L’objectif de cette thèse était triple : 1) Étudier les barrières à l’activité physique chez les enfants et adultes vivant avec le DT1 et à leurs liens avec les excursions glycémiques réellement vécues dans la vie quotidienne et d’autant plus autour de l’activité physique, 2) Chez des enfants vivant avec le DT1, comparer deux types d’exercice (exercice aérobie continu vs. intermittent intense), représentatifs de leur activité physique spontanée, et explorer leurs effets sur les variations glycémiques à l’exercice et à la récupération précoce et tardive et, 3) Mesurer la glycémie en continu, à l’exercice et à la récupération, chez des sportifs en endurance qui n’ont pas de diabète, afin de comprendre les mécanismes impliqués dans la régulation de la glycémie lors d’épreuves d’ultra-endurance et de transposer ces résultats chez des sportifs vivant avec le DT1. Les résultats montrent que : 1) Chez les enfants, plus le temps passé <54 mg.dL-1 les nuits suivant les séances d'activités physiques augmente, plus la peur de l'hypoglycémie est importante. Chez les adultes, étonnamment, ceux qui déclarent le moins l’hypoglycémie comme une barrière à l’activité physique sont ceux qui ont le plus grand pourcentage de séances d’activités physiques entraînant une baisse de glycémie; 2) Le risque hypoglycémique n’est pas supérieur lors d’un exercice continu modéré représentatif de l’activité physique spontanée des enfants et, cet exercice semble efficace pour diminuer l’hyperglycémie retrouvée les jours inactifs sur la même période de temps; 3) Un risque hyperglycémique existe lors des phases intenses de la course et pendant 48 heures de récupération lors d’un ultra-trail réalisé chez des athlètes qui n’ont pas de diabète. Ce risque hyperglycémique à la récupération pourrait être en lien avec les dommages musculaires. / Type 1 diabetes (T1D) is characterized by the autoimmune destruction of the insulin-producing ß-cells of the islets of Langerhans in the pancreas, leading to a state of chronic hyperglycemia. Despite very sophisticated management of the disease, based on functional insulin therapy, people living with T1D are frequently subject to hypoglycemic and hyperglycemic episodes because of difficulties in adapting insulin treatment, particularly during physical activity. Physical activity has many health benefits, whether or not you have diabetes. However, in the context of T1D, glycemic excursions during physical activity may lead to barriers to physical activity in this population or may limit the sporting performance of athletes living with T1D. The aim of this thesis was threefold: 1) Investigate the barriers to physical activity in children and adults living with T1D and their links with the glycemic excursions actually experienced in daily life and all the more so around physical activity, 2) In children living with T1D, compare two exercise modalities (continuous aerobic exercise vs. intense intermittent), representative of their spontaneous physical activity, and explore their effects on glycemic variations during exercise and early and late recovery and, 3) Measure glycemia continuously, during exercise and recovery, in endurance athletes without diabetes in order to understand the mechanisms involved in regulating glycaemia during ultra-endurance events and transpose these results to athletes living with T1D. The results show that: 1) In children, the greater the time spent <54 mg.dL-1 on the nights following physical activity sessions, the greater the fear of hypoglycemia. Surprisingly, among adults, those who least reported hypoglycemia as a barrier to physical activity were those who had the highest percentage of physical activity sessions resulting in a drop in blood glucose levels; 2) The risk of hypoglycemia is no greater during continuous moderate exercise representative of the spontaneous physical activity of children, and this exercise appears to be effective in reducing the hyperglycemia found on inactive days over the same period of time; 3) A hyperglycemic risk exists during the intense phases of the race and during 48 hours of recovery during an ultra-trail run carried out in athletes who do not have diabetes. This hyperglycemic risk during recovery could be related to muscle damage.

Reduction in dopamine receptor D2, has been associated with insufficient brain reward, food addiction, obesity, and type 2 diabetes (T2D). Our aim was to assess whether the genetic variability responsible for this reduction is associated with poor dietary compliance and life style habits in T2D patients. Genetic-analysis was done for 109 T2D individuals who completed a 24-week randomized clinical trial and were assigned to follow either a low-GI or a high-fibre diet. Polymorphisms of TaqIA and C957T were compared with physical and biochemical measures. Regardless of dietary treatments, individuals with the C957T-T allele and the TaqIA-A2 allele were significantly associated with blood pressure reduction. Carriers of the T allele significantly lowered their body mass index (BMI) over the 24-week trial. Our findings suggest that the presence of the TaqIA-A2 allele is associated with a decrease in blood pressure. The C957T-T allele was associated with decrease in pressure and body weight.

Reduction in dopamine receptor D2, has been associated with insufficient brain reward, food addiction, obesity, and type 2 diabetes (T2D). Our aim was to assess whether the genetic variability responsible for this reduction is associated with poor dietary compliance and life style habits in T2D patients. Genetic-analysis was done for 109 T2D individuals who completed a 24-week randomized clinical trial and were assigned to follow either a low-GI or a high-fibre diet. Polymorphisms of TaqIA and C957T were compared with physical and biochemical measures. Regardless of dietary treatments, individuals with the C957T-T allele and the TaqIA-A2 allele were significantly associated with blood pressure reduction. Carriers of the T allele significantly lowered their body mass index (BMI) over the 24-week trial. Our findings suggest that the presence of the TaqIA-A2 allele is associated with a decrease in blood pressure. The C957T-T allele was associated with decrease in pressure and body weight.

L’hyperglycémie de stress et la variabilité glycémique, consécutives à la réaction inflammatoire péri opératoire, sont associées à une morbidité et une mortalité accrues en chirurgie cardiaque. L’insulinothérapie intraveineuse administrée à l’aide de protocoles complexes, dits « dynamiques », constitue à l’heure actuelle le traitement de référence de l’hyperglycémie de stress. L’intérêt du contrôle glycémique péri-opératoire est admis par tous, sans qu’il existe de consensus véritable quant aux objectifs à atteindre, et reste très exigeant en termes de charge de soins. Dans la 1ère partie de ce travail, nous avons voulu vérifier si, 7 ans après sa mise en place, l’observance du protocole d’insulinothérapie utilisé dans notre Unité de Soins Intensifs de Chirurgie Cardiaque était conforme à celle mesurée lors de son implantation. Nous avons constaté des dérives majeures dans l’application du protocole qui ont pu être corrigées par la mise en place de mesures correctrices simples. Dans une 2ème partie du travail, nous avons cherché à évaluer si, à l’instar de la chirurgie cardiaque classique, une variabilité glycémique accrue était associée à une altération du pronostic des patients bénéficiant d’une procédure moins invasive (remplacement valvulaire aortique percutané ou TAVI). Nous avons ainsi analysé les données des patients ayant bénéficié d’un TAVI dans notre centre, et inclus dans les registres multicentriques français France et France-2. Nos résultats suggèrent une association entre une augmentation de la variabilité glycémique et un risque accru de complications cardiovasculaires majeures dans les 30 premiers jours, indépendamment de la qualité du contrôle glycémique obtenu. Enfin, dans une 3ème partie nous avons voulu savoir si exenatide, analogue de synthèse de GLP-1, permettait d’améliorer le contrôle glycémique péri opératoire en chirurgie cardiaque. Nous avons conduit un essai randomisé contrôlé de phase II/III montrant que l’administration intraveineuse (IV) d’exenatide, ne permettait pas d’améliorer la qualité du contrôle glycémique ou de réduire la variabilité glycémique par rapport à l’insuline IV, mais permettait de retarder l’administration d’insuline et de diminuer la quantité d’insuline administrée. Notre étude suggère également une diminution de la charge en soins. Du fait des données rapportées chez l’animal et dans l’infarctus du myocarde, nous avons également conduit une étude ancillaire suggérant l’absence d’effets cardioprotecteurs majeurs d’exenatide sur les lésions d’ischémie-reperfusion myocardiques, ne permettant pas d’améliorer la fonction cardiaque gauche à court et à moyen terme. L’optimisation du contrôle glycémique en chirurgie cardiaque nécessite ainsi la recherche de stratégies visant à améliorer l’observance des protocoles de soins et à réduire la variabilité glycémique. La place des analogues du GLP-1 reste à définir dans cette indication. / Stress hyperglycemia and glycemic variability are associated with increased morbidity and mortality in cardiac surgery patients. Intravenous (IV) insulin therapy using complex dynamic protocols is the gold standard treatment for stress hyperglycemia. If the optimal blood glucose target range remains a matter of debate, blood glucose control using IV insulin therapy protocols has become part of the good clinical practices during the postoperative period, but implies a significant increase in nurse workload. In the 1st part of the thesis, we aimed at checking the nurse-compliance to the insulin therapy protocol used in our Cardiac Surgery Intensive Care Unit 7 years after its implementation. Major deviations have been observed and simple corrective measures have restored a high level of nurse compliance. In the 2nd part of this thesis, we aimed at assessing whether blood glucose variability could be related to poor outcome in transcatheter aortic valve implantation (TAVI) patients, as reported in more invasive cardiac surgery procedures. The analysis of data from patients who undergone TAVI in our institution and included in the multicenter France and France-2 registries suggested that increased glycemic variability is associated with a higher rate of major adverse events occurring between the 3rd and the 30th day after TAVI, regardless of hyperglycemia. In the 3rd part if this thesis, we conducted a randomized controlled phase II/III trial to investigate the clinical effectiveness of IV exenatide in perioperative blood glucose control after coronary artery bypass graft surgery. Intravenous exenatide failed to improve blood glucose control and to decrease glycemic variability, but allowed to delay the start in insulin infusion and to lower the insulin dose required. Moreover, IV exenatide could allow a significant decrease in nurse workload. The ancillary analysis of this trial suggested that IV exenatide did neither provide cardio protective effect against myocardial ischemia-reperfusion injuries nor improve the left ventricular function by using IV exenatide. Strategies aiming at improving nurse compliance to insulin therapy protocols and at reducing blood glucose variability could be suitable to improve blood glucose control in cardiac surgery patients. The use of the analogues of GLP-1 in cardiac surgery patients needs to be investigated otherwise.