Orientador: Denise Madalena Palomari Spolidorio / Banca: Elaine Maria Sgavioli Massucato / Banca: Antonio Olavo Cardoso Jorge / Resumo: O objetivo deste estudo foi avaliar os efeitos do tratamento periodontal em pacientes diabéticos do tipo 2 sobre alterações de fluxo salivar, xerostomia, Candida spp. na saliva e candidose bucal clínica. Foram selecionados 20 pacientes diabéticos tipo 2 e 17 pacientes não-diabéticos de ambos os gêneros, com idade média entre 37 e 55 anos, portadores de doença periodontal crônica. Após exame clínico para avaliação das condições clínicas periodontais, presença de xerostomia e presença clínica de candidose bucal, amostras de saliva foram coletadas para mensuração do fluxo salivar (mL/min), contagem das colônias de Candida spp. (UFC/mL) e identificação das espécies. Esse procedimento foi realizado antes da terapia periodontal (baseline), que consistiu em raspagem e alisamento radicular, instrução de higiene bucal e motivação do paciente, aos 30 e 90 dias após a mesma. Os resultados demonstraram que os pacientes diabéticos apresentaram maior ocorrência de xerostomia e de candidose bucal, sendo estes colonizados por várias espécies de Candida spp. com predominância de C. albicans, sem no entanto, implicar no desenvolvimento da candidose clinicamente. A terapia periodontal, a motivação do paciente e a instrução de higiene bucal foram importantes para melhorar as condições clínicas periodontais e evitar a formação de reservatórios intrabucais de infecção. / Abstract: In order to investigate the effect of periodontal therapy, in type 2 diabetes mellitus subjects about salivar flow rates, presence of xerostomia, presence of Candida species in the saliva and presence of buccal candidose, twenty type 2 diabetes mellitus subjects and seventeen no-diabetes mellitus subjects, with medium age among 33 to 55 years, presenting generalized chronic periodontal disease were selected. After initial clinical exam to analyze periodontal parameters, xerostomia and buccal candidose presence, saliva samples were assessed to quantify as millimeters of saliva generated per minute (mL/min), account yeasts by colony forming units per mL (CFU/mL) and identificated species. That procedure was accomplished before periodontal therapy (baseline) that it consisted in scaling and root planning, oral hygiene instructions and patient's motivation to the thirty and ninety days after these. Diabetics subjects showed to having hyposalivation in similar levels in no-diabetics groups and in all the analyzed periods, higher prevalence of xerostomia and higher occurrence of buccal candidose. Candida albicans were the prevalent yeast at all periods in both groups, but the presence of yeasts in saliva not implied in the development of buccal candidose. Concluded that the periodontal therapy, the patients' motivation and the buccal hygiene instructions improve periodontal conditions and avoid the formation of microbial reservoirs in mouth. / Mestre

O objetivo do presente estudo foi avaliar o efeito de um programa de treinamento de potência muscular na capacidade funcional e equilíbrio, na função neuromuscular, no perfil lipídico, controle glicêmico e no nível de qualidade de vida de idosos com diabetes mellitus tipo 2 (DM2). Para tanto, foram avaliados 21 sujeitos (68,2 ± 3,1 anos), divididos em dois grupos: grupo intervenção (GI) (n=11) e grupo controle (GC) (n=10). Os sujeitos do GI realizaram treinamento de potência muscular, com sessões bissemanais, o GC realizou alongamento muscular, uma vez na semana, ambos por um período de 12 semanas. O treino de potência muscular foi realizado para os principais grupos musculares, sendo os exercícios executados da maneira mais rápida possível durante a fase concêntrica. O grupo muscular alvo foi o quadríceps. As variáveis dependentes foram avaliadas antes (momento 1), 8 semanas (momento 2 - equilíbrio dinâmico e estático) e após (momento 3) o período de intervenção O GC realizou alongamento muscular de membros superiores, tronco e membros inferiores. Para a análise dos dados foi utilizado um teste t de Student para comparação dos grupos no momento pré treinamento, para amostras independentes. A comparação de médias foi realizada com ANOVA de duas vias para medidas repetidas, utilizando um post hoc de Bonferroni para as variáveis que foram realizadas em três momentos. Os efeitos avaliados foram os fatores tempo e grupo, bem como a interação desses fatores. Para as variáveis colesterol LDL e potência de pico (calculada por fórmula), como houve diferença entre os grupos pré-treinamento, foi realizada uma ANCOVA. Um nível de significância de α ≤ 0,05 foi adotado para as análises. Os resultados demonstraram que houve uma melhora significativa (p≤0,05) para o GI na variável de equilíbrio dinâmico, avaliada pelo teste de alcance funcional, do momento 2 para o momento 3, após as 12 semanas de treinamento, o GC não apresentou modificações (p>0,05) em nenhum dos três momentos. As variáveis de equilíbrio estático não apresentaram efeitos significativos (p>0,05). Na bateria de testes Short Physical Performance Battery (SPPB), o GI apresentou uma diminuição no tempo para a realização do teste de velocidade da marcha (p<0,05) após as 12 semanas de intervenção. No teste de levantarse da cadeira, houve um efeito significativo do tempo (p<0,05), bem como, no score total da bateria de testes SPPB (p=0,001), em que os dois grupos demonstraram melhoras pós-treinamento. A espessura muscular e qualidade muscular apresentaram um efeito do tempo (p<0,05), demonstrando que ambos os grupos apresentaram melhoras. A variável neuromuscular de eco intensidade não apresentou efeito significativo (p>0,05), bem como a variável de composição corporal, gordura visceral. Para o teste de força dinâmica, realizado através do teste de 1 repetição máxima (1-RM) houve um incremento significativo, após 12 semanas de treinamento para o GI (p<0,05). O pico de torque apresentou efeito do tempo significativo (p<0,05) em ambos os grupos. Quanto à taxa de produção de torque não foram identificados efeitos significativos (p>0,05). No salto com contra movimento (CMJ) ocorreu um ganho significativo (p<0,05), em que o GI apresentou incrementos pós 12 semanas de treinamento, as outras variáveis do salto (potência média e potência de pico) apresentaram efeitos significativos (p<0,05), quando calculadas por fórmula. A hemoglobina glicada e o LDL melhoraram significativamente (p<0,05) para os dois grupos, após o treinamento. Para as demais variáveis sanguíneas não foi encontrado valores significativos. A qualidade de vida, avaliada pelo questionário de avaliação da qualidade de vida no diabetes (DQOL) demonstrou melhora significativa (p<0,05) para o GC após intervenção, não ocorrendo o mesmo com o GI. Por fim, o treinamento de potência muscular foi eficaz para demonstrar ganhos significativos nos testes de equilíbrio dinâmico, na bateria de testes funcionais e no CMJ. / The aim of the present study was to evaluate the effect of a power training program on functional fitness and balance, neuromuscular function, lipid profile, glycaemic control and quality of life level of elderly people with type 2 diabetes mellitus (T2DM). For that, 21 subjects were evaluated (68.2 ± 3.1 years), who were allocated into two groups: intervention group (IG, n=11) and control group (CG, n=10). IG subjects performed power training sessions two times per week whereas CG performed muscle stretching sessions once a week, both for a period of 12 weeks. Power training program was performed for the main muscle groups, in which the exercises were executed as fast as possible during the concentric phase. Quadriceps was the target muscle group. Dependent variables were assessed before (moment 1), at the 8th week (moment 2 – dynamic and static balance) and after (moment 3) intervention period. CG performed muscle stretching for upper limbs, trunk and lower limbs. For data analysis, a Student t test was used for comparison of the groups in the pretraining moment, for independent samples. The comparison of the means was performed with two-way ANOVA for repeated measures, with post hoc of Bonferroni for the variables that were performed in three moments. The effects evaluated were time and group factors, as well as the interaction between these factors As there was difference between groups in the pre-training, for LDL cholesterol and peak power (calculated by formula) variables an ANCOVA was performed. An α ≤ 0.05 was adopted for analyses. The results demonstrated that there was a significant improvement (p≤0.05) for IG in the dynamic balance variable, evaluated through functional reach test, from moment 2 to moment 3, after the 12 weeks of training, whereas CG did not show modifications (p>0.05) in none of the moments. Static balance variables did not show significant effects (p>0.05). In Short Physical Performance Battery (SPPB) tests, IG showed a decrease in the time factor for the performance of the gait speed test (p<0.05) after the 12 weeks of intervention. In the sit-up test, there was a significant effect of time (p<0.05), as well as in the total score of the SPPB tests battery (p=0.001), in which both groups demonstrated improvements after training. Muscle thickness and muscle quality showed an effect of time (p<0.05), demonstrating that both groups presented improvements. Neuromuscular variable of echo intensity did not show significant improvements (p>0.05), as well as the body composition variable, visceral fat. For dynamic strength test, performed through 1 repetition maximum (1-RM) test, there was a significant increment after the 12 weeks of training for IG (p<0.05). Peak torque showed a significant effect of time (p<0.05) in both groups. Regarding rate of torque production, no significant effects were identified (p>0.05). In the countermovement jump (CMJ) test, there was a significant gain (p<0.05), in which IG showed increments after the 12 weeks of intervention, and the other jump variables (mean power and peak power) showed significant effects (p<0.05), when calculated by formula. Glycated hemoglobin and LDL significantly improved (p<0.05) for both groups after training. For the remaining blood variables, significant values were not found. Quality of life, assessed through Diabetes Quality of Life Measure questionnaire (DQOL), demonstrated significant improvement (p<0.05) for CG after the intervention, which did not occur for IG. Lastly, power training program was efficient in demonstrating significant gains in dynamic balance tests, in functional tests battery and in CMJ.

Subclinical inflammation plays a pivotal role in the development of obesity- related complications including type 2 diabetes mellitus, hypertension and cardiovascular diseases. Macrophages are considered important players participating in the initiation and progression of subclinical inflammation within as well as outside of adipose tissue. The first part of this dissertation thesis was focused on macrophage characterization and their quantitative and qualitative changes accompanying metabolic improvements after bariatric surgery. We have demonstrated that the number of macrophages in subcutaneous adipose tissue is reduced regardless of their M1 or M2 polarization manifested as positivity of both the M1- associated CD40 antigen and the M2-associated CD163 and CD206 antigens 6 months after bariatric surgery. Thus, as suggested by previously published data, subcutaneous adipose tissue macrophages seem to have a mixed phenotype. We further confirmed a higher number of non- classical monocytes, which play a role in the control of vascular integrity, in obese subjects as well as a classical monocyte-derived origin of CD163 positive monocytes. Our data also support the previous suggestion of the soluble form of CD163 antigen being a suitable marker of metabolic complications of obesity. The second part...

Objetivo Avaliar, em indivíduos com diabetes (DM), a resposta de glicose e triglicerídeos duas horas após a ingestão de uma carga alimentar (CA) e sua associação com características clínicas e a presença de doenças crônicas. Metodologia Foram incluídos 915 indivíduos com DM, participantes da linha de base do estudo ELSA-Brasil. Coleta de sangue foi realizada em jejum e duas horas após o consumo da CA, contendo 455 kcal; 14 g de gordura saturada e 47 g de carboidratos. Regressão linear foi utilizada para investigar preditores dos níveis de excursão (diferença entre níveis pós-carga e de jejum) de glicemia e trigliceridemia (variáveis dependentes). Regressão logística foi realizada para descrever a associação da excursão de glicemia e trigliceridemia (variáveis independentes) e a presença de complicações do DM (doença coronariana, infarto, angina, acidente vascular cerebral, ou insuficiência cardíaca). Resultados A mediana da glicemia de jejum foi de 150 (123–198) mg/dL e da excursão de glicose foi 45 (16–79) mg/dL, enquanto que a trigliceridemia de jejum foi de 140 (103–199) mg/dL e a excursão de triglicerídeos foi de 26 (11–45) mg/dL. Maiores excursões de glicemia foram associadas com duração do DM (incremento de 5,7 mg/dL, IC95% 3,7–7,6, a cada 5 anos de doença), uso de insulina (58,5 mg/dL, IC95% 45,43–71,55), outro medicamento para DM (13,6 mg/dL, IC95% 2,5–24,8), idade (4,1 mg/dL, IC95% 0,43–7,69, a cada 10 anos), nível de glicose basal (5,2 mg/dL, IC95% 1,0–4,1, a cada 25 mg/dL); o índice de massa corporal associou-se a menor excursão (-6,8 mg/dL, IC95% -9,7 a -3,85, a cada 5 kg/m²). Maior excursão de trigliceridemia esteve associada com glicemia em jejum (2,5 mg/dL, IC95% 1,64–3,38, a cada 25 mg/dL), e menor excursão associada com triglicerídeos de jejum (-2,97 mg/dL, IC95% -3,24 – -2,69, a cada 25 mg/dL). Conclusão A resposta pós-prandial esteve associada ao tempo de doença, à necessidade de insulina ou outro medicamento para DM, ao índice de massa corporal, além da idade e níveis basais de glicose e triglicerídeos. As excursões de glicose e triglicerídeos estiveram associadas a presença de comorbidades potencialmente tidas como complicações do DM. / Objective We aimed to assess, in individuals with diabetes (DM), the excursions of glucose and triglyceride levels two hours after consumption of a food load (FL) and their association with clinical characteristics and the presence of chronic diseases. Design and Methods We included 915 subjects with DM, participants of in the ELSA-Brazil cohort. Blood sampling was performed at fasting and two hours after consumption of a 455 kcal, 14 g saturated fat and 47 g carbohydrate FL. Linear regression was used to investigate predictors of levels of excursion (difference between post-load and fasting levels) of glucose and triglycerides (dependent variables). Logistic regression was performed to describe the association of glucose excursion and triglycerides excursion (independent variables) and the presence of DM complications (coronary heart disease, myocardial infarction, angina pectoris, stroke, or heart failure). Results The median fasting glucose was 150 (123-198) mg/dL and glucose excursion was 45 (16-79) mg/dL, whereas fasting triglycerides was 140 (103-199) mg/dL and triglycerides excursion was 26 (11-45) mg/dL. Increase of glucose excursion were associated with DM duration (increase of 5.7 mg/dL, 95% CI 3.7 to 7.6, each 5 years of disease), insulin use (58.5 mg/dL, 95% CI 45.43 to 71.55), use of another drug for DM (13.6 mg/dL , 95% CI 2.5 to 24.8), age (4.1 mg/dL, 95% CI 0.43 to 7.69, each 10 years), fasting glucose (5.2 mg/dL, 95% CI 1.0 to 4.1, each 25 mg/dL) and body mass index (-6.8 mg/dL, 95% CI -9.7 to -3.85, each 5 kg/m²). The triglycerides excursion was associated with fasting glucose (2.5 mg/dL, 95% CI 1.64 to 3.38, each 25 mg/dL) and fasting triglycerides (-2.97 mg/dL, 95% CI -3.24 to -2.69, each 25 mg/dL). In logistic regression models adjusting for gender, age, fasting glucose, duration of diabetes, use of insulin and/or other drug for DM, the excursion of glucose was marginally associated with the presence of any complication of diabetes and coronary heart disease. Conclusion Greater glycemic postprandial response was positively associated with indicators of less pancreatic reserve and negatively associated with obesity, while and the size of the response in triglycerides presented only minimal associations. Associations of excursion size with diabetes complications were present.

Introdução: A medida do percentual de gordura corporal (PGC) sofre a influência de diversos fatores (obesidade severa, acúmulo excessivo de gordura no abdomen, hidratação, etc), dependendo da técnica utilizada, podendo comprometer o desempenho das mesmas. Muitos destes fatores estão frequentemente presentes nos pacientes com DM tipo 2, o que torna essencial o estudo da acurácia destes métodos nesta população. Objetivo: Avaliar a Bioimpedância (BIA) e as Dobras Cutâneas (DC) como métodos de estimativa da gordura corporal em pacientes com DM tipo 2, comparando-os com a Absorciometria de Raios X de Dupla Energia (DXA), como método de referência. Métodos: Neste estudo de acurácia diagnóstica, os pacientes foram submetidos à avaliação da composição corporal através da BIA (InBody 230, Biospace, Coréia), das DC (Lange, Fórmulas de Petroski e de Durnin) e da DXA (Lunar - iDXA). Para avaliação clínica foram analisados o controle metabólico (glicêmico e perfil lipídico) e pressórico e pesquisadas as complicações crônicas do DM. Resultados. Foram avaliados 133 pacientes (76 mulheres; idade: 63,6 ± 9,1 anos, duração do DM: 15,5 ± 10,3 anos; IMC: 29,2 ± 3,6), sendo que o PGC médio foi de 42,4 ± 4,8% nas mulheres e 31,1 ± 4,7% nos homens (p<0,001). A correlação do PGC estimado pela BIA e pelas DC com o estimado pela DXA foi, respectivamente r=0,93 (p<0,001) e r=0,81 (p<0,001). A BIA subestimou o PGC em 1,4 ± 3,2 (p<0,05) nas mulheres e 2,3 ± 3,3% (p<0,05) nos homens, quando comparada a DXA, sendo estas diferenças menos acentuadas nos pacientes com IMC≥ 30 kg/m2 (Gráficos de Bland-Altman). As DC subestimaram o PGC quando calculado com a Fórmula de Petroski, (3,7 ± 4,0% [p<0,05] nas mulheres e 1,55 ± 3,8% [p<0,05] nos homens) e superestimaram quando calculado com a Fórmula de Durnin ajustada para a idade, sendo que este ultimo apenas nas mulheres (1,8 ± 4,5% [p<0,05]). Na análise das curvas ROC, a área sob a curva da BIA foi 0,945 nas mulheres e 0,897 nos homens. Para as DC, utilizando as diferentes fórmulas, as áreas sob a curva variaram de 0,611 a 0,673 nas mulheres e foram 0,960 nos homens. Conclusão: Para a avaliação da composição corporal de pacientes com DM tipo 2, tanto a BIA como as DC (dependendo da fórmula) subestimam o PGC, comparados a DXA, mas em valores não clinicamente relevantes. A BIA apresentou uma boa acurácia em ambos sexos. Já a medida pelas DC mostrou acurácia semelhante, mas apenas nos homens. / Objective. To evaluate the performance of bioimpedance (BIA) and skinfold thickness as methods to estimate percentage body fat (PBF) in patients with Type 2 diabetes, comparing them to Dual Energy X-Ray Absorptiometry (DXA), as a reference standard. Research Design and Methods. In this study of diagnostic accuracy, the patients were submitted to evaluation of body composition with BIA (InBody 230, Biospace, Korea), skinfold thickness (Lange caliper) and DXA (Lunar - iDXA). PBF estimated by skinfold thickness was calculated with three equations: Petroski, Durnin & Womersley (DW) gender-adjusted and DW age-adjusted. Clinical evaluation consisted of the metabolic (glycemic and lipid profile) and blood pressure control, as well as the search for diabetic chronic complications. Results. One hundred and thirty-three patients were evaluated (76 women; age: 63.6 ± 9.1 years, duration of diabetes: 15.5 ± 10.3 years; body mass index [BMI]: 29.2 ± 3.6 kg/m2). PBF estimated by DXA was 42.4 ± 4.8% in women and 31.1 ± 4.7% in men (p<0.001). The correlation of the PBF estimated by BIA and by skinfold thickness with that estimated by DXA was, respectively, 0.93 (p<0.001) and 0.81 (p<0.001). BIA underestimated the PBF at 1.4 ± 3.2 (p<0.05) in women and 2.3 ± 3.3% (p<0.05) in men, compared to DXA, and these differences were less pronounced in patients with BMI ≥ 30 kg/m2 (Bland-Altman Plots). PBF calculated by Petroski’s equations was underestimated in 3.7 ± 4.0% [p<0,05] in women and 1.55 ± 3.8% [p<0.05] in men; and overestimated in 1.8 ± 4.5% [p<0.05] when calculated using DW equations age-adjusted only in women. The area under the ROC curves for BIA as a method to identify patients with increased PBF was 0.945 (p<0.001) in women and 0.897 (p<0.001) in men. The area under the ROC curves for skinfold thickness varied from 0.611 to 0.673 (all p>0.05) in women and was 0.960 (all P<0,05) in men. Conclusion. In patients with type 2 diabetes, both BIA and skinfold thickness underestimated PBF, when compared to DXA, at values that ranged from 1.4 to 2.3% and 1.5 to 4.5%, respectively. BIA was accurate in both sexes as a method to estimate PBF and to identify patients with increased PBF. On the other hand, PBF estimated by skinfold thickness was similarly accurate, but only in males.

Objective: To elaborate a quantitative food frequency questionnaire (FFQ) for patients with type 2 diabetes. Design: Dietary data using 3-day weighed diet records (WDR) from 188 outpatients with type 2 diabetes were used to construct the list of usually consumed foods. Foods were initially clustered into eight groups: “cereals, tubers, roots, and derivatives”; “vegetables”; “fruits”; “beans”; “meat and eggs”; “milk and dairy products”; “oils and fats”, and “sugars and sweets”. The frequency of food intake and the relative contribution of each food item to the total energy and nutrient intakes were calculated. A food was included if it contributed at least 80% to total energy or nutrient content in its respective food group. Portion sizes were determined according to the 25th, 50th, 75th, and 95th percentiles of intake for each food item. Setting: GNE - Group of Nutrition in Endocrinology - cohort - Southern Brazil. Subjects: Outpatients with type 2 diabetes. Results: A total of 62 food items were selected based on the 3-day WDR and another 27 foods or their preparation options and nine beverages were included after the expert examination, and accounted for 95% of total energy and nutrient intakes. Also, a portfolio with food photos of each included food item and its portion sizes was created to support the patients in identifying the consumed portion. Conclusions: We developed a practical quantitative FFQ and portfolio with photos of 98 food items covering the past 12 months of the most commonly consumed food items. This dietary method will be valuable to assess the usual diet pattern of patients with type 2 diabetes in Southern Brazil.

O objetivo do presente estudo foi analisar o efeito do treinamento aeróbico periodizado realizado em ambientes aquático ou terrestre sobre parâmetros de estado oxidativo, inflamatórios e epigenéticos em sangue periférico de sujeitos adultos com diabetes mellitus tipo 2 (DMT2). Pacientes com DMT2 sedentários (55-64 anos de idade) randomizados foram alocados em dois grupos, um grupo realizou treinamento aeróbico aquático e outro grupo realizou treinamento aeróbico terrestre. Os programas de treinamento aeróbico intervalado foram realizados três vezes por semana com duração de 45 minutos cada sessão por 12 semanas, que consistiu em caminhada e/ou corrida em piscina funda realizada pelos indivíduos do grupo de exercícios aquáticos ou caminhada e/ou corrida em pista atlética realizada pelos indivíduos do grupo de treinamento terrestre. Os treinamentos em ambos os meios apresentaram uma periodização similar; as intensidades foram determinadas a partir do segundo limiar ventilatório (LV2) de cada indivíduo. O protocolo consistiu de quatro mesociclos com três semanas cada um, durante três meses. O sangue periférico foi coletado antes e imediatamente depois da primeira e da última sessão de exercício, assim foram avaliados os efeitos agudo da primeira sessão, agudo em indivíduos treinados, além do treinamento crônico. Foram avaliados parâmetros de estado oxidativo, por meio do conteúdo de espécies reativas, do dano aos lipídeos através do nível de 8-isoprostanos e formação de substâncias fluorescentes, assim como danos às proteínas a partir do conteúdo dos resíduos de triptofano e tirosina. Além disso, a capacidade antioxidante total (TRAP) foi avaliada, assim como a atividade de enzimas antioxidantes superóxido dismutase (SOD), catalase (CAT) e a glutationa peroxidase (GPX). Ainda, foram avaliados parâmetros inflamatórios através dos níveis das interleucinas 6 (IL6), interleucina 1β (IL1β e interleucina 10 (IL10). Foi avaliada a atividade global da enzima histona desacetilase (HDAC). Houve uma diminuição do conteúdo das espécies reativas e do nível de isoprostanos após a primeira sessão de exercício, assim como após a última sessão de exercício, indicando um efeito agudo do exercício mesmo nos indivíduos treinados. Em relação à atividade das enzimas antioxidantes, ocorreu uma redução da atividade da GPX após as 12 semanas de treinamento e as atividades da SOD e da CAT diminuíram após a primeira sessão de exercício e após as 12 semanas de treinamento, sem nenhum efeito sobre o conteúdo das espécies reativas. Não houve diferença significativa entre os grupos água ou terra. Após 12 semanas de treinamento em ambos os ambientes, foi observado um aumento da IL-10, uma citocina anti-inflamatória. A atividade global da enzima HDAC aumentou agudamente após a primeira e última sessão de exercício, e ocorreu uma diminuição após as 12 semanas de treinamento tanto no grupo água como no grupo terra. Em relação aos outros parâmetros avaliados, não foram observadas diferenças significativas. A partir dos resultados obtidos, podemos sugerir que o treinamento periodizado, que respeita as características individuais, tanto em meio aquático como em terrestre, é capaz de alterar parâmetros de estado oxidativo, epigenéticos e inflamatórios em sangue periférico de pacientes com DMT2. / The aim of this study was to analyze the effects of aerobic training periodization performed in aquatic or dry land environment on oxidative stress, inflammatory and epigenetic parameters in blood of subjects with type 2 diabetes mellitus (T2DM). Sedentary patients (55-64 years) diagnosed with T2DM with no regular physical activity were allocated in a water group or a dry land group through a blinded randomization. The exercise programs consisted in aerobic interval training sessions three times a week during 12 weeks involving deep-water walking or running in swimming pool with a life vest (water group) or walking or running on a track (land group). The intensities were determined by individual second ventilatory threshold, obtained through maximal effort test, performed in their specific training environment. Our protocol consists of a periodised training with four mesocycles of three weeks each during 3 months. The effects of first and last sessions, as well as, of 12 weeks training (without any effect of acute exercise) were investigated. Firstly, we evaluated several oxidative state parameters, specifically the reactive species content, the lipid peroxidation through the 8-isoprostane levels and the fluorescent substances formation, the protein damage by the content of tryptophan and tyrosine residues. Moreover, the total antioxidant capacity (TRAP) was evaluated, as well as the antioxidant enzyme activities, namely glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). There were decreases in the reactive species and isoprostane levels after the first and the last exercise session, indicating an acute effect of exercise even in trained subjects. The exercise reduced antioxidant enzyme activities without any effect on TRAP values. Interestingly, there were no significant differences between land group and water groups. Yet, it was studied the effect of our exercise protocol on blood global HDAC activity and cytokines, interleukin 6 (IL6), interleukin 1β (IL1β) and interleukin 10 (IL10), levels in type 2 diabetes patients. After 12 weeks of training in both environments, we observed an increase in IL-10, an anti-inflammatory cytokine. Interestingly, the HDAC enzyme global activity increased acutely after first and last exercise session and there was a decrease after 12 weeks of training in both water and land groups. The results suggest that the periodization exercise performed in water and dry land environments is able to improve oxidative status, inflammatory and epigenetic parameters in subjects with type 2 diabetes.

abstract: Background: Hispanic women are at high risk for Type 2 Diabetes (T2D), in part due to their high prevalence of obesity, which may influence the development of insulin resistance and disease onset. Unhealthy eating contributes to T2D risk. Dietary patterns are the combination of total foods and beverages among individual’s over time, but there is limited information regarding its role on T2D risk factors among Hispanic women. Objective: To identify a posteriori dietary patterns and their associations with diabetes risk factors (age, BMI, abdominal obesity, elevated fasting blood glucose, and hemoglobin A1c) among overweight/obese Hispanic women. Design: Cross-sectional dietary data were collected among 191 women with or at risk for T2D using the Southwestern Food Frequency Questionnaire capturing the prior three months of intake. Dietary patterns were derived using exploratory factor analysis. Regression scores were used to explore associations between dietary patterns and diabetes risk factors. Results: The patterns derived were: 1) “sugar and fat-laden”, with high loads of sweets, drinks, pastries, and fats; 2) “plant foods and fish”, with high loads of vegetables, fruits, fish, and beans; 3) “soups and starchy dishes”, with high loads of soups, starchy foods, and mixed dishes; 4) “meats and snacks”, with high loads of red meat, salty snacks, and condiments; 5) “beans and grains”, with high loads of beans and seeds, whole-wheat and refined grain foods, fish, and alcohol; and 6) “eggs and dairy”, with high loads of eggs, dairy, and fats. The “sugar and fat-laden” and “meats and snacks” patterns were negatively associated with age (r= -0.230, p= 0.001 and r= -0.298, p<0.001, respectively). Scores for “plant foods and fish” were associated with fasting blood glucose (r= 0.152, p= 0.037). There were no other statistically significant relationships between the dietary patterns and risk factors for T2D. Conclusions: A variety of patterns with healthy and unhealthy traits among Hispanic women were observed. Being younger may play an important role in adhering to a dietary pattern rich in sugary and high-fat foods and highlights the importance of assessing dietary patterns among young women to early identify dietary traits detrimental for their health. / Dissertation/Thesis / Doctoral Dissertation Exercise and Nutritional Sciences 2018

De part leur dimension élevée, les données de puces à ADN nécessitent l’application de méthodes statistiques pour en extraire une information pertinente. Dans le cadre de l’étude des différences entre deux agonistes de PPAR (Peroxisome Proliferator-Activated Receptor), nous avons sélectionné trois méthodes de sélection de variables : T-test, Nearest Shrunken Centroids (NSC) et Support Vector Machine – Recursive Feature Elimination. Ces méthodes ont été testées sur des données simulées et sur les données réelles de l’étude PPAR. En parallèle, une nouvelle méthodologie, MetRob, a été développée afin d’améliorer la robustesse ce ces méthodes vis à vis de la variabilité technique des puces à ADN, ainsi que leur reproductibilité. Cette nouvelle méthodologie permet principalement d’améliorer la valeur prédictive positive, c’est-à-dire la confiance accordée aux résultats. La méthode NSC s’est révélée la plus robuste et ce sont donc les résultats de cette méthode, associée à MetRob, qui ont été étudiés d’un point de vue biologique. / The microarray technology provides high dimensional data that need to be statistically treated for extracting relevant information. Within the context of the study of the differences between two PPAR (Peroxisome Proliferator-Activated Receptor) agonists, we selected three feature selection methods : T-test, Nearest Shrunken Centroids (NSC) and Support Vector Machine – Recursive Feature Elimination. These methods were tested on simulated and on real data. At the same time, a new methodology, MetRob, was developed in order to improve the robustness of these methods towards the technical variability of microarrays, as well as their reproducibility. This new methodology mainly improves the positive predictive value, which means the confidence in the results. The NSC method was found to be the most robust. The results of the association of MetRob and NSC were thus studied from a biological point of view.

In type 2 diabetes the concentration of glucose in the blood is increased, and tissues like fat and musclebecome less sensitive to insulin. These two phenomena are interrelated, but since the glucose-insulininterplay is highly complex, many aspects are still not understood. Here, a model-based approachmight help. Nevertheless, also a model-based approach has a limited impact, unless models for thesub-systems can be combined into a model for the whole-body regulation. Such a multi-level,module-based model is referred to as a hierarchical model, and this thesis is a proof-of-principle studyfor the future development of such models. We have extended one of the best available models for the whole-body regulations, to include azoomable module for the fat tissue. The first step was to implement the whole-body model in thesoftware MathModelica, which support hierarchical modeling. Second, the originally mergedinsulin-responding module was sub-divided, so that a fat tissue was singled out. Third, a model for theinput-output profile for the fat tissue was developed by combining mechanistic knowledge withexisting and novel data from human fat cells. Finally, this detailed model was fitted to the profile of theoriginal fat model, and inserted in the whole-body model, with negligible effect on the whole-bodysimulations. The resulting model has the ability to translate mechanistically oriented simulations on the biochemicallevel, which is the level were drugs act, to the whole-body level, which is of clinical interest. This is aquantum leap forward for modeling, and understanding, glucose homeostasis and type 2 diabetes.