La fibrose kystique (FK) est une des maladies rares la plus fréquente au Canada avec un âge médian de survie de 50.9 ans. Toutefois, l'amélioration de l’espérance de vie est associée à l'émergence de complications secondaires telles que le diabète associé à la FK (DAFK). Présent chez 25 à 40% des adultes, il augmente de 6 fois le risque de morbidité et de mortalité. Plusieurs études sur des populations atteintes de diabète de type 2 ont démontrés les bienfaits de programmes d’exercices combinés (aérobie et résistance) sur l’amélioration du contrôle glycémique. L’objectif de l’étude visait à déterminer si un programme d’exercices combinés permettait d’améliorer les anomalies de la tolérance au glucose et le contrôle glycémique chez les patients atteints de FK. Méthodologie: 18 adultes atteints de FK, sédentaires avec une intolérance au glucose ont été recrutés pour cette étude (8 hommes, 10 femmes, âge: 33 ± 9.4 ans, FEV1 71.5% pred ± 12.5, IMC 23.57 kg/m2 ± 3,4). Les participants ont été assignés au hasard à un groupe contrôle ou exercice. Les tests suivants ont été réalisés avant et après l’intervention : VO2max, HGPO, mesure de l'endurance et de la force musculaire, ainsi qu’un questionnaire sur la qualité de vie. Résultats: 14 participants ont complété le protocole. Les participants du groupe exercice ont amélioré leur valeur de glycémie plasmatique à la 2e heure de l’HGPO (-2.34 +/- 0.87 mmol/L; p <0.01; CI 99.22%), à la 1re heure de l’HGPO (-2.0 mmol/L; p<0.05) et ont présenté une réduction de 17.2% (p<0.05) de l’aire sous la courbe de glucose. Conclusion: Un programme d'exercices combinés améliore le contrôle glycémique chez les patients atteints de FK. Cette approche thérapeutique non-pharmacologique pourrait offrir une intervention ayant le potentiel de retarder l'apparition de DAFK. / Cystic fibrosis (CF) is one of the most common rare diseases in Canada with a median age of survival of 50.9 years. However, the improvement in life expectancy is associated with the emergence of secondary complications such as CF related diabetes (CFRD). Present in 25 to 40 % of adults, CFRD is associated with decreased lung function and weight as well as a 6 times increase in risk of morbidity and mortality. CFRD is primarily caused by insulinopenia, however, insulin resistance contribution remains controversial in CF. Recent studies in type 2 diabetes described an improvement of glycemic control in patients undertaking combined exercise program (aerobic & resistance). In CF, an improvement in insulin sensitivity may result in improved glucose tolerance. There is currently no study demonstrating that exercise improves glucose tolerance in patients with CF. The aim of this study is to determine, in CF patients, if a combined exercise program is beneficial to improve glucose values at the 2nd hour of the OGTT. Method: 18 sedentary adults with CF and with abnormal glucose tolerance were recruited for this study (8 men, 10 women, age: 33 ± 9.4 years, FEV1 71.5% pred ± 12.5, BMI 23.57 kg/m2 ± 3.4). Participants were randomly assigned to a control or exercise group. VO2max, OGTT, muscular endurance and strength, and quality of life were measured pre and post intervention. Results: 14 participants completed the protocol. Participants from exercise group improved their plasmatic glucose at the 2nd hour of OGTT (-2.34 +/- 0.87 mmol/L; p < 0.01; CI 99.22%), at 1st hour of OGTT (-2.0 mmol/L; p<0.05) and presented a reduction of 17.2% (p<0.05) in the total glucose area under the curve. Conclusion: Combined exercise program improves glycemic control in CF patients. This non pharmacological approach could have the potential to delay the onset of CFRD.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-07-16T20:49:37Z No. of bitstreams: 1 Danielle da Silva Dias.pdf: 3090914 bytes, checksum: d346273638612b707bd90d03e883db70 (MD5) / Made available in DSpace on 2018-07-16T20:49:37Z (GMT). No. of bitstreams: 1 Danielle da Silva Dias.pdf: 3090914 bytes, checksum: d346273638612b707bd90d03e883db70 (MD5) Previous issue date: 2017-10-19 / The aim of the present study was to evaluate the impact of combined exercise training on the development of cardiovascular and neuroimmune dysfunctions induced by fructose overload in sedentary hypertensive (SH), SHR + fructose (HF) and SHR + fructose + training (Treadmill + ladder, 60 days, 40-60% of maximal capacity) (HFTC). The groups were divided into subgroups evaluated at 7, 15, 30 and 60 days (n=6/group/time). Fructose was offered in drinking water (10%). Metabolic, hemodynamic, autonomic, inflammatory, and oxidative stress parameters were evaluated. Regarding the metabolic profile, the HF group showed increase in white adipose tissue in relation to the H group and the HFTC group diminished these values values at 60 days (HF: 1.91± 0.10 vs. H: 1.61±0.11 and HFTC: 1.42±0.13 g). The HF group presented reduction in insulin sensitivity (HF: 3.15±0.2 vs. H: 3.96±0,1 and HFTC: 4.32±0.2 %/min) at 60 days in relation to H and HFTC groups. The HF group increased triglycerides (TG) when compared to H group at 60 days of protocol (HF:139±7 vs. H: 106±5 and HFTC:107±8 mg/dL). TG were lower in the HFTC group than in the HF group at 60 days. Fructose consumption (HF) induced a further increase in mean arterial pressure (MAP) at 30 and 60 days in SHR (HF-30 days: 1534 e HF-60 days: 184±4 vs. H-30 days: 1413 e H-60 days: 1653 mmHg). On the other hand, combined exercise training reduced MAP in 30 and 60 days of fructose overload in relation to the HF group (HFTC: 142±8 and 167±6 mmHg). There was a decrease on heart rate variability (VAR-PI) in 7 days and 60 days in the HF group (10.5±1.3 and 40.81± 6.12 ms2) in relation to the H group (23±1.5 and 59.7 ±3.4 ms2); the HFTC group did not presented this impairment (26.8±2.1 and 70.4±5.9 ms2). In addition, the HF group had a lower alpha index (spontaneous baroreflex) at 7 days compared to the H group (0.23±0.03 vs. 0.35±0.01 ms/mmHg), which was not observed in the HFTC group. There was an increase in IL-6 and TNFα in cardiac tissue at 15, 30 and 60 days in the HF and HFTC groups compared to the H groups. The HFTC group presented higher IL-10 values in the heart at 7 days compared to the HF group (28±1 vs. 16±1 pg/mg of protein). The HF group presented increase in cardiac lipoperoxidation at 30 and 60 days in relation to the H group. The HFTC group decreased lipoperoxidation compared to HF group at 60 days (1302±58 vs. 1956±215 cps/mg protein) and there was also reduction in protein oxidation in this time. In addition, there was an increase in NADPH oxidase in the HF group at 60 days when compared to the H group and reduction in this parameter in the HFTC group in relation to the HF group at the same time (H: 0.18±0.02; HF: 0.46 ±0.04; HFTC 0.35 ±0.03 μm/mg protein). Considering the redox balance, the HFTC group presented increase in this evaluation in 7, 15, 30 and 60 days in relation to H and HF groups. Our results show that only 7 days of fructose consumption impaired the autonomic control of the circulation, followed by reduction in plasma nitrites and increase in cardiac IL-6 and TNF- in 15 days, culminating in increased cardiac protein and lipids damage, which are probably associated with the appearance of cardiometabolic dysfunctions after 30 days of protocol in SHR. In addition, combined exercise training prevented the development of autonomic dysfunction in this model, which probably promoted favorable neuroimmune changes and oxidative stress profile, culminating in a marked attenuation of cardiometabolic dysfunctions in SHR submitted to fructose consumption. Together our findings reinforce the role of the autonomic nervous system in the genesis of cardiometabolic dysfunctions and evidence an important role of combined exercise training in the prevention of these alterations. / O objetivo do presente estudo foi avaliar o impacto do treinamento físico combinado no desenvolvimento das disfunções cardiovasculares e neuroimunes induzidas pela sobrecarga de frutose em ratos hipertensos (SHR). Para isto SHR foram divididos em grupos: SHR (H), SHR+frutose (HF) e SHR+frutose+treinamento físico combinado (esteira+escada, 60 dias, 40-60% da capacidade máxima) (HFTC). A frutose foi oferecida na água de beber (10%). Parâmetros metabólicos, hemodinâmicos, autonômicos, inflamação e estresse oxidativo foram avaliados em subgrupos (n=6 grupo/tempo) em 7, 15, 30 e 60 dias. Com relação ao perfil metabólico o grupo HF aumentou o peso do tecido adiposo branco em relação ao grupo H e o grupo HFTC reduziu esses valores em 60 dias (HF: 1,91± 0,10 vs. H: 1,61±0,11 e HFTC: 1,42±0,13 g). Houve redução de sensibilidade à insulina no grupo HF em 60 dias (HF: 3,15±0,2 vs. H:3,96±0,1 e HFTC: 4,32±0,2 %/min) em relação aos grupos H e HFTC. O grupo HF apresentou aumento de triglicérides (TG) quando comparado ao grupo H em 60 dias protocolo (HF:139±7 vs. H: 106±5 e HFTC:107±8 mg/dl), o que não foi observado no grupo HFTC. O consumo de frutose (grupos HF) induziu um aumento adicional na pressão arterial média (PAM) em 30 e 60 dias de protocolo nos SHR (HF-30 dias: 1534 e HF-60 dias: 184±4 vs. H-30 dias: 1413 e H-60 dias: 1653 mmHg). Por outro lado, o treinamento físico combinado (HFTC: 142±8 e 167±6 mmHg) reduziu a PAM em 30 e 60 dias de sobrecarga de frutose em relação aos grupos HF. Não foram observadas diferenças na frequência cardíaca basal entre os grupos. Houve diminuição da variabilidade da frequência cardíaca (VAR-IP) em 7 dias e em 60 dias nos grupos HF (10,51,3 e 40,816,12 ms2) em relação aos grupos H (231,5 e 59,73,4 ms2); o grupo HFTC não apresentou esse prejuízo (26,82,1 e 70,45,9 ms2). Além disso, o grupo HF apresentou menor índice alfa (barorreflexo espontâneo) em 7 dias em relação ao grupo H (0,230,03vs. 0,350,01 ms/mmHg), o que não foi observado no grupo HFTC. Houve aumento de IL-6 e TNFα no coração em 15, 30 e 60 dias nos grupos HF e HFTC em relação aos respectivos grupos H. O grupo HFTC apresentou maiores valores de IL-10 cardíaco em 7 dias em relação ao grupo HF (281 vs. 161 pg/mg de proteína). Os grupos HF apresentaram aumento de lipoperoxidação cardíaca em 30 e 60 dias em relação aos grupos H; o grupo HFTC diminuiu a lipoperoxidação em relação ao grupo HF em 60 dias (130258 vs.1956215 cps/mg proteína), além de reduzir a oxidação de proteínas em tecido cardíaco nesse mesmo tempo. Adicionalmente, houve um aumento na NADPH oxidase no grupo HF em 60 dias em relação ao grupo H e redução no grupo HFTC em relação ao grupo HF no mesmo tempo (H: 0,180,02; HF: 0,460,04; HFTC 0,350,03 µm/mg de proteína). No balanço redox, o grupo aos grupos H e HF apresentaram redução da razão GSH/GSSG em 7, 15, 30 e 60 dias em relação aos grupos HFTC. Nossos resultados evidenciam que com apenas 7 de consumo de frutose houve prejuízo no controle autonômico da circulação, que foi seguida por redução de nitritos, aumento de IL-6 e TNF- no coração em 15 dias, culminando em aumento de lesão à proteínas e lipídeos nesse tecido, que provavelmente se associam ao aparecimento das disfunções cardiometabólicas a partir de 30 dias de protocolo nos SHR. Adicionalmente, o treinamento físico combinado impediu o desenvolvimento da disfunção autonômica neste modelo, o que provavelmente promoveu alterações neuroimunes e de perfil de estresse oxidativo favoráveis, culminado em marcante atenuação das disfunções cardiometabólicas em SHR submetidos ao consumo de frutose. Em conjunto nossos achados reforçam o papel do sistema nervoso autônomo na gênese das disfunções cardiometabólicas e evidenciam um importante papel do treinamento físico combinado na prevenção dessas alterações.