Introdução: Doenças crônicas não transmissíveis representam as principais morbidades da atualidade, dentre estas o diabetes mellitus (DM) tipo 2 e a depressão, as quais encontram-se frequentemente associadas. Ambas contribuem para complicações cardiovasculares e mortalidade. Há evidências de que intervenções comportamentais trazem benefícios cardiometabólicos e psicológicos. Objetivos: Para avaliar intervenção no estilo de vida, este estudo incluiu: 1) revisão sistemática e metanálise destinada a investigar os efeitos de intervenções no estilo de vida na melhora da depressão em indivíduos de risco ou com diabetes mellitus tipo 2; 2) comparação do efeito de duas intervenções no estilo de vida sobre o risco cardiometabólico e na retenção dos indivíduos ao programa; 3) análise do papel da depressão na resposta cardiometabólica às intervenções, mediada pela inflamação e; 4) avaliação do efeito residual 9 meses após término das intervenções quanto às respostas de variáveis clínicas, qualidade de vida (QV) e depressão. Métodos: Para revisão sistemática os principais bancos de dados bibliográficos foram pesquisados, sendo a meta-análise conduzida por modelos de efeito aleatório. O estudo longitudinal incluiu adultos pré-diabéticos, submetidos a 18 meses de intervenção tradicional (TRD) ou interdisciplinar com psicoeducação (INT) para mudanças em hábitos de vida, sendo os dados coletados (antropometria, pressão arterial, perfil bioquímico e marcadores de inflamação PCR, TNF-, adiponectina) no momento basal, 9 e 18 meses, bem como 9 meses após o término do acompanhamento (27 meses). Dieta foi avaliada por recordatórios de 24h, atividade física pelo Questionário Internacional de Atividade Física , depressão pelo Inventário de Beck e a QV pelo Medical Outcome Study Short Form 36 itens. Os momentos e os tipos de intervenção foram comparados por modelos lineares de efeitos mistos. Teste t Student foi aplicado para comparações entre médias, qui-quadrado para avaliar frequências e coeficientes de Pearson ou Spearman para correlações, complementados por análise de regressão múltipla. Resultados: Revisando sistematicamente o efeito na depressão de intervenções, encontrou-se na meta-análise, que em indivíduos com DM, mudanças no 10 estilo de vida reduzem significativamente os escores de depressão (SMD=-0.151; IC: - 0.253, -0.049). Entre os 183 indivíduos que compuseram nossa amostra, 46 por cento tinham sintomas depressivos, e eram predominantemente do sexo feminino, com maior adiposidade e menores escores de QV. Após 18 meses de ambas as intervenções, houve redução nos escores de depressão. Comparada à TRD, a INT provocou maior redução no consumo energético, adiposidade, níveis de pressão arterial, e maior aumento na atividade física e concentrações de adiponectina. Desistentes aos 18 meses apenas da TRD apresentaram pior perfil de saúde e maior escore de depressão, comparados aos que se mantiveram neste subgrupo. Em regressão linear múltipla, a depressão apenas nas mulheres associou-se a não melhora metabólica ao longo de 18 meses e tal associação não foi mediada pela inflamação. Aos 27 meses, apenas a adiposidade diferiu entre as intervenções. A QV e depressão mantiveram-se com melhora aos 27 meses em ambas. Discussão: 1) A metanálise sugere que intervenções no estilo de vida para manejar o DM são efetivas na melhora da depressão. É essencial que este grupo de risco seja rastreado regularmente. 2) Intervenção interdisciplinar com abordagem psicoeducativa mostrou-se útil em atenuar o risco cardiometabólico e na retenção de indivíduos com pior perfil de saúde. 3) Presença de depressão pode predizer menor chance de melhora no perfil cardiometabólico em longo prazo, particularmente entre as mulheres. Maior atenção ao diagnóstico e manejo da depressão deve ser dada a este subgrupo de maior risco. 4) Intervenção interdisciplinar melhorou a QV e reduziu depressão, bem como manteve o peso dos participantes após 9 meses da interrupção do programa, contribuindo para melhora continuada das condições de saúde biopsicossociais. Conclusão: Em geral, intervenção no estilo de vida é eficaz para melhorar o perfil metabólico e depressão, além de ser capaz de manter em tratamento indivíduos com pior estado de saúde. Não se pode comprovar ou afastar que a inflamação media tais benefícios. Esta estratégia é promissora para motivar indivíduos de maior risco na adoção de hábitos saudáveis em longo prazo. Profissionais da saúde e gestores de políticas públicas devem conhecer os efeitos deletérios da depressão no manejo de indivíduos de risco cardiometabólico. Diagnóstico e tratamento da depressão devem contribuir para otimizar o tratamento de distúrbios cardiometabólicos. / Introduction: Nowadays non-communicable chronic diseases, such as diabetes mellitus and depression, are major public health problems worldwide. These conditions are commonly associated and contribute to cardiovascular complications and mortality. Previous studies showed that motivational interviews may improve cardiometabolic and psychological aspects. Objectives: In order to assess lifestyle intervention this study includes: 1) Systematic review and meta-analysis to verify effect of lifestyle interventions on depression; 2) to compare effects of two lifestyle interventions in the cardiometabolic risk and in retention of at-risk individuals; 3) to analyze influence of depression in cardiometabolic response to interventions mediated by inflammation and, 4) to assess residual effect at 9 months after completion of interventions according to clinical variables, quality of life and depression. Methods: In the systematic review major bibliographic databases were searched. Meta-analysis was conducted by random-effects model. The effect of method, duration, and frequency of the interventions were determined via subgroup analyses. Our longitudinal study includes prediabetic adults, submitted to one of two lifestyle interventions (TRD:Traditional or INT:Interdisciplinary). Data were collected (anthropometry, blood pressure, biochemical profile and inflammation markers CRP, TNF-, adiponectin) at baseline, 9th and 18th month, as well as 9 months after completion of interventions (observational phase). Diet was evaluated by 24h recalls and physical activity by IPAQ. Depression was measured by Beck Inventory and quality of life (QOL) by SF-36. Linear mixed-models were applied for longitudinal analysis. Student t-test was used to compare means and chi-square for frequencies. Pearson coefficient was used to select variables for multiple regression analysis. Results: Through systematic review and meta-analysis, we found that lifestyle interventions to manage diabetes reduce depression scores (SMD= -0.151; IC: -0.253, -0.049). Among 183 individuals, 46 per cent had depression, 12 mostly women, with greater adiposity and lower QOL scores. After 18 months of both interventions, depression scores were reduced. Compared to TRD, the INT had greater reductions in energy intake, adiposity, blood pressure levels, likewise higher adiponectin and physical activity levels. Only in the TRD individuals who dropped out showed worse health profile and increased depression scores, compared to those who non dropped out. In multiple regressions, depression in women increased the chances of non-improvement in blood pressure and glucose levels. This association was not mediated by inflammation. In the observational phase, adiposity, but not other parameters, differed between groups over time. QOL and depression were maintained improved with both interventions. Discussion: 1) This meta-analysis suggests that lifestyle interventions intended to manage DM were effective in improving depression. Regular screening for depression is essential for this at-risk subset; 2) The interdisciplinary psychoeducation-based intervention proved to be useful for reducing cardiometabolic risk profile, and improving retention of individuals with worse profile. This approach represents a feasible strategy for motivating at-risk individuals to adopt a long-term healthy lifestyle; 3) Depression predicted a lower chance of improving long-term cardiometabolic risk, particularly in women. We suggest that screening and management of depression as part of lifestyle interventions can potentially improve cardiometabolic responses. 4) Interdisciplinary intervention improved QOL and reduced depression scores, as well as maintained weight loss 9 months after interruption of intervention, which may contributes to the sustained improvement. Conclusion: In general, interdisciplinary intervention was effective to improve cardiometabolic risk and depression, likewise to retain individuals with worse health status. It was not found benefits mediated by inflammation reduction. This strategy may motivate individuals at high risk to adopt healthier life habits. Health professionals must be aware about deleterious effects of depression to manage individuals at risk. Diagnosis and treatment of depression may contribute to optimize treatments of cardiometabolic diseases.

DE CAMARGO, M. A. G. Fatores preditores do alcance das metas do programa de intervenção no estilo de vida em nipo-brasileiros de Bauru - SP. 2008. 99 f. Dissertação (Mestrado em Saúde na Comunidade). Faculdade de Medicina de Ribeirão Preto-USP. Objetivos: Identificar fatores associados ao alcance das metas de um programa de intervenção no estilo de vida em Nipo-Brasileiros de Bauru, SP. Metodologia: Os fatores associados ao alcance das metas (perda de peso de 5%, prática de 150 minutos de atividades físicas semanal, consumo alimentar com teor de gordura saturada inferior a 10% das calorias totais, consumo diário de 400g de frutas, verduras e legumes), após 12 meses de intervenção foram investigados em modelos de regressão logística ajustados, As avaliações do estilo de vida e perfil de saúde foram conduzidas no início do estudo e após 12 meses de seguimento. Resultados: No total, 458 nipo-brasileiros, 56% do sexo feminino, 84% de 2ª geração, idade média (DP) de 60 (11) anos foram analisados. Foram incluídos nos modelos múltiplos para cada desfecho investigado os indivíduos com excesso de peso (n=329), que reportaram não terem o hábito da prática de 150 minutos de atividades físicas semanal (n=278), consumo alimentar com teor de gordura saturada superior a 10% das calorias totais (n=107) e consumo diário inferior a 400g de frutas, verduras e legumes (n=265). Após 12 meses, 11% dos indivíduos com excesso de peso alcançaram a meta de perda de peso, 24, 55 e 16% dos participantes alcançaram as metas de prática de atividades físicas, teor da dieta de gordura saturada e consumo de frutas, verduras e legumes, respectivamente. Após ajuste por variáveis de confusão, maior razão de chance [OR (95%)] para o alcance da meta de perda de peso foi verificada entre mulheres [2,4 (1,3; 4,5)], e menor razão de chance entre portadores de diabetes, hipertensão e dislipidemia [0,4 (0,1; 0,8)] e indivíduos classificados em estágio de mudança de pré-contemplação / contemplação para redução do consumo de carnes vermelhas [0,4 (0,2; 0,9)]. Os participantes de 2ª geração apresentam menor razão de chance para o alcance da meta do consumo de frutas, verduras e legumes [0,3 (0,1; 0,9)]. Nenhuma associação foi verificada para as metas da prática de atividades físicas e de gordura saturada. Conclusões: Entre os Nipo-Brasileiros, as estratégias do programa de intervenção no estilo de vida foram mais eficientes no alcance das metas entre as mulheres, indivíduos de 1ª geração, não portadores de morbidades e participantes classificados nos estágios de mudança de ação / manutenção para a redução do consumo de carnes vermelhas. Palavras-chave: intervenção no estilo de vida, Nipo-Brasileiros; metas / Objectives: To verify factors associated with reaching goals in a lifestyle intervention program in Japanese-Brazilians living in Bauru, SP. Methodology: The factors associated with reaching the goals (5% of weight loss, practice of 150 minutes of physical activity/ week, less than 10% of energy from saturated fat and the intake of 400g of fruits and vegetables daily), after 12 months of intervention were investigated by adjusted logistic regression models. The assessments of lifestyle and health profile were conducted at baseline and after 12 months of intervention. Results: In total, 458 Japanese-Brazilians, 56% females, 84% of 2nd generation, mean (SD) age of 60 (11) were investigated. At baseline, 329 individuals were overweight, 278 reported less than 150 minutes/ week of physical activity, 107 reported food intakes with more than 10% of calories from saturated fat and 265 reported less than 400g of fruits and vegetables/day, and were included in the models. After 12 months, 11% of the overweight individuals reached the goal of weight loss, and 24, 55, and 16% of the participants reached the goals of the practice of physical activity, and intakes of saturated fat and fruits and vegetables, respectively. After adjustments for potential confounding variables, higher odds ratios [OR (95%)] for achieving weight loss were verified among women [2.4 (1.3; 4.5)], and lower chances among individuals with diabetes, hypertension or dyslipidemia [0.4 (0.1; 0.8)], and on precontemplation / contemplation stages of change for reducing red meat intakes [0.4 (0.2; 0.9)]. Individuals of 2nd generation had lower chances of achieving the goal of fruits and vegetables intake [0.3 (0.1; 0.9)]. No associations were verified for achieving the goals of practice of physical activity and saturated fat intakes. Conclusion: Among Japanese-Brazilians, the lifestyle intervention strategies were more efficient on reaching the goals among women, individuals of 1st generation, those without diseases and participants on stages of change of action/maintenance for reducing red meat intakes. Key-words: Lifestyle intervention, Japanese-Brazilians, lifestyle goals, prevention of chronic diseases, nutrition epidemiology.

Introdução: Doenças crônicas não transmissíveis representam as principais morbidades da atualidade, dentre estas o diabetes mellitus (DM) tipo 2 e a depressão, as quais encontram-se frequentemente associadas. Ambas contribuem para complicações cardiovasculares e mortalidade. Há evidências de que intervenções comportamentais trazem benefícios cardiometabólicos e psicológicos. Objetivos: Para avaliar intervenção no estilo de vida, este estudo incluiu: 1) revisão sistemática e metanálise destinada a investigar os efeitos de intervenções no estilo de vida na melhora da depressão em indivíduos de risco ou com diabetes mellitus tipo 2; 2) comparação do efeito de duas intervenções no estilo de vida sobre o risco cardiometabólico e na retenção dos indivíduos ao programa; 3) análise do papel da depressão na resposta cardiometabólica às intervenções, mediada pela inflamação e; 4) avaliação do efeito residual 9 meses após término das intervenções quanto às respostas de variáveis clínicas, qualidade de vida (QV) e depressão. Métodos: Para revisão sistemática os principais bancos de dados bibliográficos foram pesquisados, sendo a meta-análise conduzida por modelos de efeito aleatório. O estudo longitudinal incluiu adultos pré-diabéticos, submetidos a 18 meses de intervenção tradicional (TRD) ou interdisciplinar com psicoeducação (INT) para mudanças em hábitos de vida, sendo os dados coletados (antropometria, pressão arterial, perfil bioquímico e marcadores de inflamação PCR, TNF-, adiponectina) no momento basal, 9 e 18 meses, bem como 9 meses após o término do acompanhamento (27 meses). Dieta foi avaliada por recordatórios de 24h, atividade física pelo Questionário Internacional de Atividade Física , depressão pelo Inventário de Beck e a QV pelo Medical Outcome Study Short Form 36 itens. Os momentos e os tipos de intervenção foram comparados por modelos lineares de efeitos mistos. Teste t Student foi aplicado para comparações entre médias, qui-quadrado para avaliar frequências e coeficientes de Pearson ou Spearman para correlações, complementados por análise de regressão múltipla. Resultados: Revisando sistematicamente o efeito na depressão de intervenções, encontrou-se na meta-análise, que em indivíduos com DM, mudanças no 10 estilo de vida reduzem significativamente os escores de depressão (SMD=-0.151; IC: - 0.253, -0.049). Entre os 183 indivíduos que compuseram nossa amostra, 46 por cento tinham sintomas depressivos, e eram predominantemente do sexo feminino, com maior adiposidade e menores escores de QV. Após 18 meses de ambas as intervenções, houve redução nos escores de depressão. Comparada à TRD, a INT provocou maior redução no consumo energético, adiposidade, níveis de pressão arterial, e maior aumento na atividade física e concentrações de adiponectina. Desistentes aos 18 meses apenas da TRD apresentaram pior perfil de saúde e maior escore de depressão, comparados aos que se mantiveram neste subgrupo. Em regressão linear múltipla, a depressão apenas nas mulheres associou-se a não melhora metabólica ao longo de 18 meses e tal associação não foi mediada pela inflamação. Aos 27 meses, apenas a adiposidade diferiu entre as intervenções. A QV e depressão mantiveram-se com melhora aos 27 meses em ambas. Discussão: 1) A metanálise sugere que intervenções no estilo de vida para manejar o DM são efetivas na melhora da depressão. É essencial que este grupo de risco seja rastreado regularmente. 2) Intervenção interdisciplinar com abordagem psicoeducativa mostrou-se útil em atenuar o risco cardiometabólico e na retenção de indivíduos com pior perfil de saúde. 3) Presença de depressão pode predizer menor chance de melhora no perfil cardiometabólico em longo prazo, particularmente entre as mulheres. Maior atenção ao diagnóstico e manejo da depressão deve ser dada a este subgrupo de maior risco. 4) Intervenção interdisciplinar melhorou a QV e reduziu depressão, bem como manteve o peso dos participantes após 9 meses da interrupção do programa, contribuindo para melhora continuada das condições de saúde biopsicossociais. Conclusão: Em geral, intervenção no estilo de vida é eficaz para melhorar o perfil metabólico e depressão, além de ser capaz de manter em tratamento indivíduos com pior estado de saúde. Não se pode comprovar ou afastar que a inflamação media tais benefícios. Esta estratégia é promissora para motivar indivíduos de maior risco na adoção de hábitos saudáveis em longo prazo. Profissionais da saúde e gestores de políticas públicas devem conhecer os efeitos deletérios da depressão no manejo de indivíduos de risco cardiometabólico. Diagnóstico e tratamento da depressão devem contribuir para otimizar o tratamento de distúrbios cardiometabólicos. / Introduction: Nowadays non-communicable chronic diseases, such as diabetes mellitus and depression, are major public health problems worldwide. These conditions are commonly associated and contribute to cardiovascular complications and mortality. Previous studies showed that motivational interviews may improve cardiometabolic and psychological aspects. Objectives: In order to assess lifestyle intervention this study includes: 1) Systematic review and meta-analysis to verify effect of lifestyle interventions on depression; 2) to compare effects of two lifestyle interventions in the cardiometabolic risk and in retention of at-risk individuals; 3) to analyze influence of depression in cardiometabolic response to interventions mediated by inflammation and, 4) to assess residual effect at 9 months after completion of interventions according to clinical variables, quality of life and depression. Methods: In the systematic review major bibliographic databases were searched. Meta-analysis was conducted by random-effects model. The effect of method, duration, and frequency of the interventions were determined via subgroup analyses. Our longitudinal study includes prediabetic adults, submitted to one of two lifestyle interventions (TRD:Traditional or INT:Interdisciplinary). Data were collected (anthropometry, blood pressure, biochemical profile and inflammation markers CRP, TNF-, adiponectin) at baseline, 9th and 18th month, as well as 9 months after completion of interventions (observational phase). Diet was evaluated by 24h recalls and physical activity by IPAQ. Depression was measured by Beck Inventory and quality of life (QOL) by SF-36. Linear mixed-models were applied for longitudinal analysis. Student t-test was used to compare means and chi-square for frequencies. Pearson coefficient was used to select variables for multiple regression analysis. Results: Through systematic review and meta-analysis, we found that lifestyle interventions to manage diabetes reduce depression scores (SMD= -0.151; IC: -0.253, -0.049). Among 183 individuals, 46 per cent had depression, 12 mostly women, with greater adiposity and lower QOL scores. After 18 months of both interventions, depression scores were reduced. Compared to TRD, the INT had greater reductions in energy intake, adiposity, blood pressure levels, likewise higher adiponectin and physical activity levels. Only in the TRD individuals who dropped out showed worse health profile and increased depression scores, compared to those who non dropped out. In multiple regressions, depression in women increased the chances of non-improvement in blood pressure and glucose levels. This association was not mediated by inflammation. In the observational phase, adiposity, but not other parameters, differed between groups over time. QOL and depression were maintained improved with both interventions. Discussion: 1) This meta-analysis suggests that lifestyle interventions intended to manage DM were effective in improving depression. Regular screening for depression is essential for this at-risk subset; 2) The interdisciplinary psychoeducation-based intervention proved to be useful for reducing cardiometabolic risk profile, and improving retention of individuals with worse profile. This approach represents a feasible strategy for motivating at-risk individuals to adopt a long-term healthy lifestyle; 3) Depression predicted a lower chance of improving long-term cardiometabolic risk, particularly in women. We suggest that screening and management of depression as part of lifestyle interventions can potentially improve cardiometabolic responses. 4) Interdisciplinary intervention improved QOL and reduced depression scores, as well as maintained weight loss 9 months after interruption of intervention, which may contributes to the sustained improvement. Conclusion: In general, interdisciplinary intervention was effective to improve cardiometabolic risk and depression, likewise to retain individuals with worse health status. It was not found benefits mediated by inflammation reduction. This strategy may motivate individuals at high risk to adopt healthier life habits. Health professionals must be aware about deleterious effects of depression to manage individuals at risk. Diagnosis and treatment of depression may contribute to optimize treatments of cardiometabolic diseases.

Individuals with type 2 diabetes mellitus (T2DM) are at risk for developing life-threatening comorbidities such as cardiovascular disease (CVD). As a consequence, T2DM is associated with increased morbidity and mortality and decreased quality of life, thus highlighting the importance of prevention of T2DM. Further, the prevalence of T2DM is substantially greater in rural populations compared to urban populations, making rural individuals particularly appropriate targets for T2DM prevention. T2DM is a largely preventable disease that is associated with modifiable risk factors such as poor diet, sedentary lifestyle, and obesity. Lifestyle interventions to improve these modifiable risk factors have been used to decrease the risk of developing T2DM. There is little evidence that supports lifestyle interventions as a means to decrease T2DM risk in rural populations with prediabetes, the precursor of T2DM. The purpose of this dissertation was to determine whether rural-living individuals with prediabetes would improve modifiable risk factors, specifically diet quality by following a lifestyle intervention; thereby, decreasing their risk of developing T2DM. Specific aims for this dissertation were to, 1) examine and synthesize data from dietary interventions used to reduce risk of T2DM in rural populations on order to identify gaps and guide future research, 2) critically evaluate validity and reliability of indices used to determine diet quality in research, and 3) determine the effect of a risk reduction program on improving diet quality and glucose control (as a measure of T2DM risk) in rural adults with prediabetes and CVD risk factors. Specific aim one was achieved by a review and synthesis of literature focused on lifestyle and dietary interventions used in rural populations to decrease the risk of developing T2DM. Common goals in these studies were a decrease in weight, decrease in dietary fat and calories, and an increase in physical activity. Decreased weight and increased physical activity were demonstrated in all eight studies, and a decrease in T2DM incidence was also demonstrated in one of the studies. However, diet quality was not adequately assessed in the majority of the studies. Furthermore, none of the studies were randomized controlled trials and only half used a control group. It was concluded that research using a more robust design is needed to determine the effect of lifestyle changes, specifically diet, on T2DM risk in rural populations. Specific aim two was addressed by a critical analysis of six common indices of dietary quality. Validity and reliability of the Healthy Eating Index, the Alternative Healthy Eating Index, the DASH diet score, the Diet Quality Index-Revised, the Healthy Diet Indicator, and the Diet Quality Score were examined. Five of the six indices are valid and reliable tools for measure diet quality but all five rely on an extensive food frequency questionnaire that may be burdensome for participants. The Diet Quality Score does not provide adequate evidence to support its use in research. It was concluded that a short, reliable, and validated diet screener may be useful in research. Specific aim three was addressed by a secondary data analysis of a longitudinal, randomized controlled study of rural residents with CVD risk factors and prediabetes. Diet quality, measured by the Mediterranean Diet Adherence Screener (MEDAS), and glucose control, measured by hemoglobin A1c, were analyzed in a subpopulation of 62 participants with prediabetes. Neither diet quality nor glucose control improved between baseline, four month, and 12 month post intervention. The reliability and validity of the MEDAS in this population is not known and may have been a factor in the lack of intervention effect related to diet quality. Participants were also not informed of their prediabetes status, thus it is not known if this knowledge would have made an impact on the outcomes of the study. In addition, the small sample size limits the statistical power to determine changes between the intervention and control groups. It was concluded that further research is needed to determine if a high quality diet will reduce T2DM risk in this rural population Considering the disproportionate prevalence of T2DM in rural populations compared to their urban counterparts, the results of this dissertation demonstrate a continued need for interventions that decrease modifiable risk factors associated with this disease. Interventions that target obesity, poor diet quality, and sedentary lifestyles in at-risk rural populations that are culturally tailored are needed to decrease risk of developing T2DM and the comorbidities associated with this preventable disease.

The global epidemic of obesity is rapidly becoming a major public health problem in many parts of the world. Unhealthy diets and physical inactivity are two modifiable risk factors for prevention of obesity and its associated chronic diseases. Their influence on muscle energy metabolism and fat mass is not completely elucidated. A decreased capacity for fatty acid oxidation (FAO) may be a metabolic risk factor for weight gain and is found to be depressed in obese individuals; and exercise training may promote an increased capacity for FAO. In addition to the interest in whole-body FAO, the role of site specific lipid accumulation including visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular lipids (IMCL) has become a focus of interest because of their reported association with insulin resistance (IR), a key metabolic defect associated with obesity and type 2 diabetes mellitus (T2DM). However, ambiguity persists regarding the importance of IMCL as a metabolic substrate for energy production in obesity. A better understanding of the factors regulating FAO, body fat distribution and IMCL mobilisation is important for the development of interventions allowing effective treatment of conditions in which these are disturbed. The study of individuals with metabolic myopathies can give more information about the energy metabolism of muscle. McArdle disease (MD) affects glucose availability to muscle for energy production. Investigations into IMCL storage and mobilisation in MD have not been reported. The aims of this thesis are to investigate 1) the effects of weight-loss via dietary restriction plus modest but clinically-relevant exercise training on FAO, body fat distribution and mobilisation of IMCL during exercise in obese non-diabetic adults; 2) the effect of an exercise training intervention on IMCL storage and mobilisation in a subject with MD. All obese subjects underwent a 4 month lifestyle intervention with weekly meetings with a dietitian and an exercise physiologist. Of the 92 subjects, 73 completed the intervention. They showed significant decreases in body weight (8%), fat mass (14%) and total cholesterol (5%). The exercise prescription of 1500 kcal.week-1 resulted in variable compliance with the prescription (1224 ± 1085 kcal.week-1) measured by heart rate monitor. Those who did most exercise and also those who had less weekly variability in their exercise, had greater reductions in body weight and fat mass. The total activity energy expenditure measured by accelerometry did not change post-intervention but there was a reduction in low intensity activity and an increase in moderate and high intensity activity. A submaximal treadmill test and resting metabolic rate (RMR) using indirect calorimetry was measured before and after the intervention to investigate factors regulating FAO and energy expenditure. Subjects showed increases in FAO without change in energy expenditure for the same walking speed post intervention, but the volume of exercise completed during the intervention was not associated with these changes. To investigate body fat distribution in obesity, VAT, IHL and soleus muscle IMCL was measured in a sub-group of 18 males by magnetic resonance imaging (MRI) and spectroscopy (MRS) along with measurement of maximal aerobic capacity. Fitness increased significantly with significant decreases in VAT (29%) and IHL (54%), without significant change in IMCL. Subjects who had the greatest decrease in VAT were those who exercised for longer durations during the intervention. IHL was the only measure of excess lipid that correlated with IR. The measurement of IMCL before and after 1-hour of cycle ergometer exercise showed no significant mobilisation of IMCL either at baseline or after the lifestyle intervention. The intensity of the acute exercise was adjusted to correspond to each individual’s maximal fatty acid oxidation (MFAO) which increased by over 60% post intervention. In the subject with MD, an 8 week exercise training intervention without dietary intervention increased IMCL stores by 27%, but there was no marked change in IMCL with acute exercise at both time points. The findings of this thesis demonstrate that a clinically relevant and achievable lifestyle intervention incorporating weight loss through diet and objectively measured exercise can achieve improvements in blood lipid profile, body composition and FAO. The differential effects of the intervention on the various fat depots and their associations to metabolic markers suggest that individualised strategies may be required dependent upon body fat distribution. The non detection of mobilisation of IMCL by MRS suggests that these lipids may not be present as a substrate source in this population but rather an ectopic lipid depot related to increased energy consumption in diet. The relatively low capacity for FAO in both the obese and MD subjects may have affected the results. This thesis discusses implications for clinical practice, discusses novel findings related to the energy metabolism in obesity and MD and informs clinical and basic science about important future directions.

The global epidemic of obesity is rapidly becoming a major public health problem in many parts of the world. Unhealthy diets and physical inactivity are two modifiable risk factors for prevention of obesity and its associated chronic diseases. Their influence on muscle energy metabolism and fat mass is not completely elucidated. A decreased capacity for fatty acid oxidation (FAO) may be a metabolic risk factor for weight gain and is found to be depressed in obese individuals; and exercise training may promote an increased capacity for FAO. In addition to the interest in whole-body FAO, the role of site specific lipid accumulation including visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular lipids (IMCL) has become a focus of interest because of their reported association with insulin resistance (IR), a key metabolic defect associated with obesity and type 2 diabetes mellitus (T2DM). However, ambiguity persists regarding the importance of IMCL as a metabolic substrate for energy production in obesity. A better understanding of the factors regulating FAO, body fat distribution and IMCL mobilisation is important for the development of interventions allowing effective treatment of conditions in which these are disturbed. The study of individuals with metabolic myopathies can give more information about the energy metabolism of muscle. McArdle disease (MD) affects glucose availability to muscle for energy production. Investigations into IMCL storage and mobilisation in MD have not been reported. The aims of this thesis are to investigate 1) the effects of weight-loss via dietary restriction plus modest but clinically-relevant exercise training on FAO, body fat distribution and mobilisation of IMCL during exercise in obese non-diabetic adults; 2) the effect of an exercise training intervention on IMCL storage and mobilisation in a subject with MD. All obese subjects underwent a 4 month lifestyle intervention with weekly meetings with a dietitian and an exercise physiologist. Of the 92 subjects, 73 completed the intervention. They showed significant decreases in body weight (8%), fat mass (14%) and total cholesterol (5%). The exercise prescription of 1500 kcal.week-1 resulted in variable compliance with the prescription (1224 ± 1085 kcal.week-1) measured by heart rate monitor. Those who did most exercise and also those who had less weekly variability in their exercise, had greater reductions in body weight and fat mass. The total activity energy expenditure measured by accelerometry did not change post-intervention but there was a reduction in low intensity activity and an increase in moderate and high intensity activity. A submaximal treadmill test and resting metabolic rate (RMR) using indirect calorimetry was measured before and after the intervention to investigate factors regulating FAO and energy expenditure. Subjects showed increases in FAO without change in energy expenditure for the same walking speed post intervention, but the volume of exercise completed during the intervention was not associated with these changes. To investigate body fat distribution in obesity, VAT, IHL and soleus muscle IMCL was measured in a sub-group of 18 males by magnetic resonance imaging (MRI) and spectroscopy (MRS) along with measurement of maximal aerobic capacity. Fitness increased significantly with significant decreases in VAT (29%) and IHL (54%), without significant change in IMCL. Subjects who had the greatest decrease in VAT were those who exercised for longer durations during the intervention. IHL was the only measure of excess lipid that correlated with IR. The measurement of IMCL before and after 1-hour of cycle ergometer exercise showed no significant mobilisation of IMCL either at baseline or after the lifestyle intervention. The intensity of the acute exercise was adjusted to correspond to each individual’s maximal fatty acid oxidation (MFAO) which increased by over 60% post intervention. In the subject with MD, an 8 week exercise training intervention without dietary intervention increased IMCL stores by 27%, but there was no marked change in IMCL with acute exercise at both time points. The findings of this thesis demonstrate that a clinically relevant and achievable lifestyle intervention incorporating weight loss through diet and objectively measured exercise can achieve improvements in blood lipid profile, body composition and FAO. The differential effects of the intervention on the various fat depots and their associations to metabolic markers suggest that individualised strategies may be required dependent upon body fat distribution. The non detection of mobilisation of IMCL by MRS suggests that these lipids may not be present as a substrate source in this population but rather an ectopic lipid depot related to increased energy consumption in diet. The relatively low capacity for FAO in both the obese and MD subjects may have affected the results. This thesis discusses implications for clinical practice, discusses novel findings related to the energy metabolism in obesity and MD and informs clinical and basic science about important future directions.

L’obésité est un problème majeur de santé publique et sa fréquence en Guadeloupe, est supérieure à celle observée en France hexagonale. Les causes de l’obésité sont multifactorielles. Des formes d’obésité monogénique ont été décrites chez moins de 5 % des patients obèses d’origine européenne mais, les variations génétiques sous-jacentes à l’obésité ne sont pas totalement connues. L’obésité infantile est associée à des effets néfastes sur la santé, incluant des complications métaboliques avec l’implication de nombreuses hormones et cytokines qui jouent un rôle important dans le métabolisme glucidique et l’homéostasie énergétique.Les objectifs de ces travaux étaient les suivants.- Évaluer le profil métabolique, incluant l’étude des taux de ghréline, leptine, adiponectine et de 25-hydroxyvitamine D chez 120 enfants scolarisés répartis en trois groupes : normo-pondéraux (G1), en surpoids (G2) et obèses (G3).- Analyser, à un an, les variations des paramètres anthropométriques et métaboliques après une intervention multidisciplinaire sur le mode de vie.- Investiguer, chez 25 enfants obèses de l’étude, les mutations de gènes connus et impliqués dans les formes monogéniques de l’obésité en utilisant des techniques récentes de séquençage.- Investiguer dans une population d’adultes l’association de variants de trois gènes candidats FABP2, ADIPOQ et NPPA avec le syndrome métabolique (dont l’obésité abdominale est une des composantes) en utilisant un score de risque génétique.Les travaux réalisés dans le cadre de cette thèse apportent des données nouvelles sur le profil métabolique des enfants obèses en Guadeloupe. Ils démontrent qu’une intervention sur le mode de vie améliore ce profil et pourrait contribuer à la prévention des complications cardio-métaboliques dans cette population à haut risque d’obésité et de diabète de type 2. Les effets bénéfiques de l’accompagnement familial et de l’approche multidisciplinaire en milieu scolaire sont aussi mis en exergue. L’identification, chez ces enfants obèses, de variants, rares et peu décrits, de gènes impliqués dans les formes d’obésité monogénique plaide en faveur d’une implication de ces variants dans la survenue de l’obésité. Par ailleurs, chez l’adulte, l’existence d’un effet cumulatif des variants des gènes FABP2, ANP et ADIPOQ sur le syndrome métabolique est aussi suggérée. / Obesity is a major public health problem and its frequency in Guadeloupe is higher than that observed in mainland France. The causes of obesity are multifactorial. Monogenic forms of obesity have been described in less than 5% of obese patients of European origin, but the genetic variations underlying obesity are not fully known.Obesity in children is associated with adverse health effects, includingmetabolic complications with the involvement of many hormones and cytokines that play an important role in glucose metabolism and energy homeostasis.The objectives of this work were as follows. Evaluate the metabolic profile, including ghrelin, leptin, adiponectin and vitamin D levels in 120 schoolchildren divided into three groups: normal weight (G1), overweight (G2) and obese (G3). Analyze, at one year, variations of anthropometric and metabolic parameters after a multidisciplinary lifestyle intervention. Investigate, in 25 obese children, mutations of genes known and involved in monogenic forms of obesity using next-generation sequencing. Investigate in an adult population the association of variants of three candidate genes FABP2, ADIPOQ and NPPA with metabolic syndrome (of which abdominal obesity is one of the components) using a genetic risk score.The results in this thesis provide new data on obese children metabolic profile in Guadeloupe. They demonstrate that a lifestyle intervention improves this profile and could contribute to prevention of cardio metabolic complications in this population at high risk of obesity and type 2 diabetes. The beneficial effects of family support and the multidisciplinary approach in schools are also highlighted.The identification, in these obese children of rare and little described gene variants involved in monogenic form of obesity argues for their involvement in the occurrence of this pathology. Moreover, in adults, the existence of a cumulative effect of FABP2, ANP and ADIPOQ gene variants on metabolic syndrome is also suggested.

As morbid obesity increasingly affects Hispanic-Americans, the incidence of Roux-en-Y gastric bypass procedures (RYGB) among this population rises. Prospective research on the impact of postoperative educational interventions focused on Hispanic-Americans is needed to prevent premature weight loss plateau, weight regain, nutritional deficiencies, and relapse of obesity-related comorbidities. This randomized-controlled study evaluated the impact of a comprehensive nutrition and lifestyle education intervention (6 biweekly postoperative sessions that incorporated motivational strategies for behavioral change) as compared to a non-comprehensive approach (printed guidelines for healthy lifestyle). The variables to consider are body weight, obesity-related comorbidities (depression, diabetes, dyslipidemia, and others), nutrient status, physical activity, and eating habits in 144 morbidly-obese adult Hispanic-Americans 6 to 12 months following RYGB. Patients were randomly assigned to either the comprehensive intervention (n=72) or the comparison group (n=72). Participants (mean age 44.5 ± 13.5 years) were mainly Cuban-born females (83.3%). Intervention sessions attendance was 64%. At 12 months, both groups lost weight significantly, but those in the comprehensive intervention experienced greater excess weight loss than those in the comparison group (80% vs. 64% from preoperative excess weight, P<.001). Intervention participants were significantly more involved in physical activity (+ 14 min/week vs. – 4 min/week), had decreased depression, joint illness, and required less medication for comorbidities than comparison participants. Additionally, those in the comprehensive intervention had sustained supplement intake experiencing less folate deficiency (P=.014). The non-comprehensive intervention group significantly decreased their protein and supplement intake compared to the intervention group. Patients in the comprehensive intervention had significantly better eating habits reflected by fewer episodes of dumping syndrome, constipation, and night eating, than those in the comparison group who reported greater eating in response to negative emotions (P=.003). These findings support the importance of a comprehensive educational approach to achieve more effective weight reduction and health-related outcomes to prevent relapse of obesity-related comorbidities and nutritional deficiencies in Hispanic-Americans 6 to 12 months following RYGB.

Adventists following a plant-based diet have half the prevalence and incidence of type 2 diabetes than nonvegetarian Adventists. This study used a quantitative, correlational study design to assess if there was a significant difference in type 2 diabetes prevalence rate between Adventists and non-Adventists preprogram, and if there were significant differences in biometrics between Adventists and non-Adventists with diabetes pre- and post-Complete Health Improvement Program (CHIP). This study incorporated the social ecological model for its conceptual framework and examined pre- and postprogram changes among Adventists (n=210; 20.1%) and non-Adventists (n=836; 79.9%) with type 2 diabetes. It used secondary data from participants in the volunteer-delivered CHIP intervention from 2006 to 2012 (n=7,172), a whole foods, plant-based, vegan health program. Analysis showed a significant difference in the pre-CHIP diabetic state between the two groups in step one, but not after controlling for covariates in step two (OR=0.96 and 0.91; CI=1.21 and 1.24). A repeated measures MANOVA analysis indicated that religious affiliation (Adventist or non-Adventist) was the determining factor in improved biometric outcomes pre- and post-CHIP for TC (F(1) = 5.65; p = 0.02), and LDL (F(1) = 5.76; p = 0.02) but not for HDL (F(1) = 0.00; p = 0.99), TG (F(1) = 0.19, p = 0.67), FPG (F(1) = 2.71, p = 0.10), SBP (F(1) = 2.25; p = 0.13), DBP (F(1) = 1.20; p = 0.27), and BMI (F(1) = 1.65; p = 0.20). However, both groups improved post-CHIP in all biometrics. The implications for positive social change from this study showed that CHIP is an effective lifestyle model for improving type 2 diabetes outcomes for both Adventists and non-Adventists, a model that does not involve the use of pharmaceuticals.

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