The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

Background: Rheumatoid arthritis (RA) is characterised by excessive production of tumour necrosis factor alpha (TNFα). This leads to rheumatoid cachexia, a condition characterised by increased resting energy expenditure (REE) and loss of fat-free mass (FFM) leading to functional disability, decreased strength and balance. The aims of this research work was to: a) to develop a new REE equation in order to continuously monitor abnormal changes in REE in the RA population, b) to investigate if smoking further enhances hypermetabolism and c) to examine if the new anti-TNFα medication reverses this metabolic abnormality. Methods: 68 patients with RA were assessed for demographic and anthropometrical characteristics, REE (indirect calorimetry), body composition (bioelectrical impedance), and disease activity [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score 28 (DAS28) and health assessment questionnaire (HAQ)]. 20 of the total 68 patients, about to start anti-TNFα therapy, underwent the exact same aforementioned procedures but on three separate occasions (Baseline: two weeks prior to anti-TNFα treatment, Time-1 and Time-2: two weeks and three months, respectively, after the drug had been introduced. Results: Study 1: Based on FFM and CRP, a new equation was developed which had a prediction power of R2=0.76. The new equation revealed an almost identical mean with measured REE (1645.2±315.2 and 1645.5±363.1 kcal/day, p>0.05), and a correlation coefficient of r=0.87 (p=0.001). Study 2: Smokers with RA demonstrated significantly higher REE (1513.9±263.3 vs. 1718.1±209.2 kcal/day; p=0.000) and worse HAQ (1.0±0.8 vs. 1.7±0.8; p=0.01) compared to age and FFM matched RA non-smokers. The REE difference was significantly predicted by the interaction smoking/gender (p=0.04). Study 3: Significant increases were observed in REE (p=0.002), physical activity (p=0.001) and protein intake (p=0.001) between the three times of assessment. Moreover, disease activity significantly reduced [ESR (p=0.002), DAS28 (p=0.000), HAQ (p=0.000) and TNFα (p=0.024)] while FFM and total body fat did not change (both at p>0.05). Physical activity and protein intake were found to be significant within-subject factors for the observed REE elevation after 12-weeks on anti-TNFα treatment (p=0.001 and p=0.024, respectively). Conclusions: Findings from the first study revealed that the newly developed REE equation provides an accurate prediction of REE in RA patients. Moreover, the results from the second study showed that cigarette smoking further increases REE in patients with RA and has a negative impact on patients’ self-reported functional status. Finally, our data from the third study suggest that REE remains elevated not because of the maintenance of the RA-related hypermetabolism but due to the concomitant significant increases in physical activity and protein intake.

The purpose of this work was to further understand nutritional status, especially body weight and composition, during colorectal cancer progression. Population-based studies of colorectal cancer patients were conducted using administrative health data (primary and co-morbid diseases, demographics), and computed tomography (CT) imaging (body composition). In cohort 1, administrative health data was used to study comorbidities and nutritional status in 574 colorectal cancer patients referred for chemotherapy. Multivariate Cox regression revealed several comorbidities, performance status and weight loss 20% predicted survival. In cohort 2, a serial CT image analysis assessed longitudinal body composition changes during the last 12 months preceding death from colorectal cancer (n=34). Body composition changes were typified by exponential increases in liver metastases with concurrent accelerations of muscle and fat loss. These results have the potential to make a difference in how colorectal cancer patients are treated and researched by dietitians, oncologists, and health services researchers. / Nutrition and Metabolism

The prevalence of obesity continues to increase despite considerable research and innovation regarding treatment and management strategies. When completed as prescribed, exercise training is associated with numerous health benefits and predictable levels of weight loss. However, under free-living conditions the benefits of exercise are less consistent, suggesting that non-adherence and/or a compensatory response in non-exercise activity thermogenesis (NEAT) may be occurring. The accurate quantification of all components of total energy expenditure (TEE), including TEE itself, was imperative to elucidate the primary research question relating to the impact of exercise on TEE. In addition, the measurement of changes in body composition and the response to prescribed exercise were assessed in methodological and pilot investigations. Following this extensive background, the primary research question relating to the effect of exercise on levels of TEE and the associated implications of such a compensatory response could be more rigorously investigated. The first study investigated the variability in isotopic equilibrium time under field conditions, and the impact of this variability on estimates of total body water (TBW) and body composition when using the deuterium dilution technique. Following the collection of a fasting baseline urine sample, 10 women and 10 men were dosed with deuterium oxide (0.05g/kg body weight). Urine samples were collected every hour for 8 hours. The samples were analysed using isotope ratio mass spectrometry and time to equilibration was determined using three commonly employed data analysis approaches. Isotopic equilibrium was reached by 50, 80 and 100% of participants at 4, 6 and 8 h, respectively. The mean group equilibration times determined using the three different plateau determination methods were 4.8 ± 1.5, 3.8 ± 0.8, and 4.9 ±1.4 h, respectively. Isotopic enrichment, TBW, and percent body fat estimates differed between early sampling times (3-5 h), but not later sampling times (5-8 h). Therefore, sampling < 6 hours post dose compared to sampling ≥ 6 hours resulted in greater relative measurement error in TBW and body composition estimates. Although differences in equilibration time were apparent between the three plateau determination approaches, sampling at 6 hours or later may decrease the likelihood of error in body composition estimates resultant from incomplete isotopic equilibration in a small proportion of individuals. In the second study, the aim was to measure the self-paced walking (SPW) speed of adults ranging in body size from normal to obese. The utility of heart rate monitors to estimate the energy cost of walking was also investigated. Twenty-nine participants (12 normal-weight, 17 overweight or obese) completed two outdoor walking tests to determine their SPW speed. A walking treadmill test with stages below, at, and above the SPW speed was completed to compare the energy expenditure estimates of the Polar S610 and WM42 heart rate monitors with that from indirect calorimetry. The average SPW speed was 1.7 ± 0.1 m*sec-1, which was equivalent to an exercise intensity of 48.6 ± 9.4 %VO2max (61.0 ± 7.1 %HRmax). There was no difference in the energy expenditure estimation between indirect calorimetry (4.7 ± 0.7 kcal*kg*-1*h-1), the S610 (4.8 ± 1.3 kcal*kg*-1*h-1) and the WM42 (4.8 ± 1.6 kcal*kg*-1*h-1). It was concluded that the heart rate monitors provided reasonable energy expenditure estimates at the group level. However considerable error was evident at the individual level, explained in part by exercise heart rate and fitness level, suggesting that an individualised calibration should be performed where possible. An additional finding from this study was that 145 to 215 minutes of SPW per week, dependent upon the level of adiposity, is required to meet the current American College of Sports Medicine (ACSM) guidelines for health of 1000 kcal*wk-1. The purpose of the third study was to establish the level of adherence to a specific exercise prescription (1500 kcal*wk-1) by objectively quantifying unsupervised exercise energy expenditure (ExEE) in a group of obese women. The 16-wk lifestyle intervention consisted of weekly meetings with research staff, combined with promotion of increased ExEE (1500 kcal*wk-1) and a decreased dietary intake (-500 kcal*d-1). Twenty-nine obese females (Body Mass Index = 36.8 ± 5.0 kg*m2, Body Fat = 49.6 ± 3.7 %) from a hospital-based lifestyle intervention were included in the analysis. ExEE was estimated and monitored weekly using heart rate monitoring. Body composition was measured before and after the intervention by dual-energy x-ray absorptiometry (DXA). Results indicated free-living adherence to the exercise prescription was modest and variable, with 14% of participants achieving the 1500 kcal*wk-1. The average weekly ExEE (768 kcal*wk-1) represented 51.2% of the total amount prescribed. ExEE was correlated with changes in body weight (r = 0.65, p < 0.001) and fat mass (r = 0.65, p = 0.0002). Achievement of a 5% weight loss target was dependent on an ExEE level of 1000 kcal*wk-1 (p &lt0.001). Exercise 'adherers' (> 000 kcal*wk-1) lost more weight (-9.9 vs. -4.1 kg), more fat mass (-6.8 vs. -3.0 kg), and more waist circumference (-9.8 vs. -5.6 cm) when compared to 'non-adherers' (< 1000 kcal*wk-1). The results suggest that the extent of supervision and monitoring influenced exercise adherence rates. The variability in adherence highlights the importance of objective monitoring of ExEE. Identification of individuals not complying with program targets may enable intervention staff to provide additional support or make individualised adjustments to the exercise prescription. The fourth study investigated issues relating to the management and interpretation of accelerometry data when the device is to be used to monitor levels of daily physical activity. Given the high between-individual variability in accelerometry output for a given walking speed, the use of a more individualised approach to the data management has been suggested. In addition, accelerometry was used to compare daily physical activity patterns between a supervised and unsupervised exercise prescription of the same dose (1500 kcal*wk-1) in overweight and obese women. Total energy expenditure, activity energy expenditure, and vector magnitude increased significantly during the intervention. Time spent in very low intensity movement decreased from baseline to the intervention (p < 0.01) in both the supervised (-18.6 min*d-1) and unsupervised (-68.5 min*d-1) group, whereas time spent in high and vigorous intensity movement increased significantly from baseline to the intervention (p < 0.05 and p < 0.0001, respectively). The increase in vigorous movement was significantly greater in the supervised group when compared to the unsupervised group (+11.5 vs. +5.4 min*d-1, p < 0.05). Time spent above three different moderate-intensity walking thresholds increased from baseline to the intervention (p < 0.0001). The threshold determination approach significantly affected the resultant outcomes (p < 0.0001) such that the standard threshold was significantly different to both group-specific and individualised approaches. Significant differences were also noted in accelerometer output between treadmill and overground walking (p < 0.0001). A positive finding of this study was that two different interventions aimed at increasing physical activity levels in a group of sedentary and obese women were successful in gaining modest increases in overall daily movement. The change observed appears to be a replacement of sedentary movement with more vigorous physical activity. Collectively, the differences observed between threshold determination approaches, as well as between treadmill and overground walking, highlight the need for standardised approaches to accelerometry data management and analysis. In addition, the findings suggest that obese women may benefit from a certain degree of exercise supervision to ensure compliance, however, strategies to encourage these women to continue with the exercise on their own without supervision are essential to making a sustainable long-term change to their lifestyles. The final study aimed to assess whether obese women compensate for structured exercise by decreasing their NEAT and thereby impeding weight loss. Thirteen participants were prescribed 1500 kcal*wk-1 of exercise through a structured walking program (4 week supervised followed by 4 weeks unsupervised). The energy expenditure of the walks was quantified using individually-calibrated Polar F4 heart rate monitors. The DLW technique was used to measure TEE. Accelerometry measures were also collected throughout and represented an alternative method of quantifying changes in total daily movement patterns resultant from an increase in energy expenditure through exercise. Compliance with the exercise program was excellent, with the average compliance being 94% over the 8-week intervention. The adoption of moderate-intensity exercise in this group of obese women resulted in a 12% decrease in TEE (p = 0.01) and a 67% decrease in NEAT (p < 0.05). No significant change was observed in resting metabolic rate from baseline to the postintervention time-point. Compensation was significantly correlated with dietary report bias (r= -0.84, p = 0.001), body image (r = 0.75, p < 0.01), and bodily pain (r = -0.65, p < 0.05). A linear regression model including dietary reporting bias and the pain score explained 78% of the variation in ΔTEE. Compensators were therefore less likely to underreport their dietary intake, less likely to be self-aware of their obese state, and more likely to be experiencing pain in their daily life. Self-reported dietary intake decreased significantly during the intervention (p = 0.01) with specific decreases noted in fat and carbohydrate intake. The consequence of compensation was evidenced by a lack of significant change in body weight, body composition, or blood lipids (p > 0.05). However, positive outcomes of the study included improvement in the SF-36 scores of general health (p < 0.05) and maintenance of exercise program adherence into the unsupervised phase of the intervention. Qualitative data collected via interview indicated that 85% of participants experienced increased energy and positive feedback from peers during the intervention. This study confirms that exercise prescription needs to be prescribed with an individualised approach that takes into account level of adiposity. The goal of exercise prescription for the obese should therefore be to determine the intensity and modality of exercise that does not activate compensatory behaviours, as this may in turn negate the beneficial effects of the additional energy expenditure of exercise. This study confirms that during the initial phase of an exercise-based weight loss intervention, the majority of obese women compensated for some, if not all, the energy cost of the exercise sessions by reducing NEAT. Whether this compensatory behaviour continues beyond the first month of an exercise program, particularly after training adaptations in cardiorespiratory fitness are realised, cannot be discerned from the current study. However these results do provide a rationale for why the magnitude of weight loss achieved is often less than predicted during exercise interventions. Further research is required to examine the temporal pattern of compensation in NEAT, and the relationship between the time courses of NEAT compensation relative to physical fitness improvements. The results from this thesis support the use of activity monitors such as accelerometers during weight loss interventions to track NEAT and provide objective feedback regarding compensatory behaviours to clinicians and the obese individuals.

Introdução: O gasto energético (GE) dos indivíduos pode ser determinado por diversos métodos, dentre os quais estão a calorimetria indireta (CI) e as equações de predição. Objetivo: Comparar o gasto energético de pacientes com doença pulmonar obstrutiva crônica (DPOC) medido através da CI com o estimado pela equação de Harris-Benedict (HB). Métodos: Estudo transversal incluindo 30 indivíduos com diagnóstico médico de DPOC, segundo critérios GOLD, atendidos no Centro de Reabilitação Pulmonar do Pavilhão Pereira Filho e do ambulatório de Pneumologia, ambos do Complexo Hospitalar Santa Casa de Porto Alegre, no período de fevereiro à setembro de 2010. O gasto energético foi mensurado pela CI usando monitor específico, assim como predito pela equação de HB. Os participantes também foram submetidos à avaliação antropométrica, através dos parâmetros de peso, altura, índice de massa corporal (IMC), dobra cutânea tricipital (DCT), circunferência do braço (CB) e circunferência muscular do braço (CMB), além de aplicação da avaliação nutricional subjetiva global (ANSG), bem como verificação do consumo alimentar. Os valores encontrados foram analisados através do teste t de Student, do teste qui-quadrado de McNemar e pelo método de Bland-Altman, e expressos pela média ± desvio-padrão, com nível de significância estatística p 0,05. Resultados: Do total de 30 portadores de DPOC, 70% eram do sexo masculino com idades de 62,5 ± 11,5 anos e IMC médio de 24,2 ± 4,2kg/m². O gasto energético em repouso (GER) medido pela CI foi de 1.568 ± 234,8kcal e o estimado pela equação de HB foi de 1.312 ± 120,5kcal, com diferença estatisticamente significativa entre os dois métodos (p<0,001). Quanto ao gasto energético total (GET), o valor medido pela CI foi de 2.038 ± 305,23kcal e o predito pela equação de HB foi de 2.047 ± 188kcal, sem apresentar diferença estatística significativa (p=0,853) e demonstrando uma concordância de 96,7% entre os dois métodos. Relativo ao diagnóstico nutricional, ao considerarmos apenas o IMC, 3,3% dos participantes apresentavam desnutrição, 63,3% eutrofia, 23,3% sobrepeso e 10% obesidade enquanto que pelo agrupamento de parâmetros (IMC, DCT, CB, CMB e ANSG), 53,3% dos pacientes apresentaram desnutrição, 33,3% eutrofia, 10% sobrepeso e 3,3% obesidade. Conclusão: O GER foi subestimado pela equação de HB, não apresentando boa concordância com o medido pela CI. Quanto ao GET, os resultados foram significativamente semelhantes demonstrando boa concordância entre os dois métodos. Em relação ao estado nutricional, talvez o IMC não seja suficiente para avaliar a real condição de pacientes com DPOC. / Introduction: The energy expenditure (EE) of individuals can be determined by various methods, among which are the indirect calorimetry (IC) and the prediction equations. Objective: To compare the energy expenditure of patients with chronic obstructive pulmonary disease (COPD) measured by the IC estimate by the Harris-Benedict equation (HB). Methods: Cross sectional study including 30 individuals diagnosed with COPD according to GOLD criteria, seen in the Pulmonary Rehabilitation Center of the Pereira Filho and outpatient pulmonology, both of Santa Casa Hospital Complex of Porto Alegre in the period from February to September 2010. Energy expenditure was measured by IC using a specific monitor, as predicted by the HB equation. Participants also underwent anthropometric assessment, through the parameters of weight, height, body mass index (BMI), triceps skinfold thickness (TSF), mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC), and application subjective global nutritional assessment (SGA) and to determine food consumption. The values were analyzed using the Student t test, chi-square, McNemar and the Bland-Altman and expressed as mean + standart deviation, with statistical significance level p 0.05. Results: Of 30 patients with COPD, 70% were male, aged 62.5 ± 11.5 years and average BMI of 24.2 ± 4.2kg/m². The resting energy expenditure (REE) measured by IC was 1568 ± 234.8kcal and estimated by the HB equation was 1312 ± 120.5kcal, with a statistically significant difference between the two methods (p<0.001). As for the total energy expenditure (TEE), the value measured by ICwo methods (p <0.001). As for the total energy expenditure (TEE), the value measured by IC was 2038 ± 305.23kcal and foretold the HB equation was 2047 ± 188kcal, no statistical significant difference (p=0.853) and showed a concordance of 96,7% between the two methods. Concerning the nutritional diagnosis, we consider only the BMI, 3.3% of participants had malnutrition, 63.3% were eutrophic, 23.3% overweight and 10% were obese while the grouping of parameters (BMI, TSF, CB, CMB and SGA), 53.3% of patients suffered from malnutrion, 33.3% were eutrophic, 10% overweight and 3.3% obese. Conclusion: REE was underestimated by the HB equation, not a good agreement with that measured by IC. As for the GET, the results were significantly similar showing good agreement between the two methods. In relation to nutritional status, BMI may not be sufficient to evaluate the actual condition of patients with COPD.

L’inactivité physique, facteur de risque de pathologies chroniques, est un problème majeur de santé publique. Des méthodes validées sont essentielles pour mesurer l’activité physique (AP). Le 1er objectif de cette thèse était de préciser la validité des techniques de mesure de l’AP. Le 2nd objectif visait à comparer les résultats de questionnaires de rappel évaluant le contexte aux mesures objectives de l’AP. Le 3ème objectif était d’évaluer l’intérêt des méthodes objectives pour l’étude de certains déterminants de l’AP. Nous avons mesuré par différentes méthodes (calorimétrie indirecte, actimètres, questionnaires de rappel) l’AP, en vie libre, de sujets peu actifs (personnes obèses, diabétiques ou sédentaires). Nos résultats illustrent l’intérêt des méthodes objectives mais aussi leurs limites, ainsi que l’intérêt des données déclaratives pour évaluer le contexte. Le choix des méthodes influence le résultat des études et doit tenir compte des caractéristiques de l’AP des sujets les moins actifs. Ce choix participe à l’amélioration des connaissances des liens entre AP et santé pour guider la promotion de l’AP des segments peu actifs de la population. / Physical inactivity is a risk factor for chronic diseases and is recognized as a major public health issue. Validated methods are essential to describe accurately physical activity (PA). The 1st aim of this work was to assess the validity of PA assessment techniques. The 2nd was to compare the results of recall questionnaires evaluating PA context with objective PA measures. The 3rd was to assess the usefulness of objective methods in the assessment of some determinants of PA. We measured free-living PA with different methods (indirect calorimetry, actimetry, recall questionnaire assessing PA context) in individuals with low PA levels (obese subjects, type 2 diabetic patients, inactive subjects). The results highlight the usefulness but also the limits of the methods of PA measurement in daily life conditions. The choice of an assessment method will influence the study results and must be adapted to the unique ways in which the least active individuals engage in PA. Selecting the appropriate method is a pre-requisite for improving our knowledge on the relations between PA and health in order to guide PA promotion in the least active segments of the population.

No description available.

Human ageing is accompanied by characteristic metabolic and endocrine changes, including altered hormone profiles, insulin resistance and deterioration of skeletal muscle. Obesity and diabetes may themselves drive an accelerated ageing phenotype. Untangling the causal web between ageing, obesity and diabetes is a priority in order to understand their aetiology and improve prevention and management. The role of biological ageing in determining the risk of obesity and associated conditions has often been examined using mean leukocyte telomere length (LTL), a marker of replicative fatigue and senescence. However, considering phenotypes which represent different domains of biological and functional ageing as exposures for obesity and related traits could allow the elucidation of new understudied phenotypes relevant to cardio-metabolic risk in the wider population. This PhD considers the causal role of (1) hand grip strength (HGS), a marker of overall strength and physical functioning, and (2) resting energy expenditure, an indicator of overall energy metabolism and the major component of daily energy expenditure, in cardio-metabolic risk. I also characterise a new and readily-quantifiable marker of age-related genomic instability, mosaic loss of the Y chromosome (mLOY). Observational evidence implicates each of these phenotypes in cardio-metabolic conditions and intermediate phenotypes. However, it is not possible to infer causality from these observational associations due to confounding and reverse-causality. Mendelian randomisation offers a solution to these limitations and can allow the causal nature of these relationships to be investigated. Using population-based data including UK Biobank, this thesis presents the first large-scale genetic discovery effort for each trait and provides new biological insight into their shared and separate aetiology. I used identified variants to investigate the bidirectional causal associations of each trait with cardio-metabolic outcomes, intermediate phenotypes and other related traits such as frailty and mortality. In total I identified 16 loci for hand grip strength, 19 for mLOY, and one signal for REE. I have shown that HGS is likely to be causally linked to fracture risk, and I have identified the important shared genetic architecture between mLOY, glycaemic traits and cancer. I have also demonstrated that at least one known genetic variant contributing to obesity risk acts partially via reduced REE. Overall the findings of my PhD contribute to our wider understanding of the aetiological role of ageing processes in metabolic dysfunction, and have implications for both basic science and translational applications.

Introdução: O gasto energético (GE) dos indivíduos pode ser determinado por diversos métodos, dentre os quais estão a calorimetria indireta (CI) e as equações de predição. Objetivo: Comparar o gasto energético de pacientes com doença pulmonar obstrutiva crônica (DPOC) medido através da CI com o estimado pela equação de Harris-Benedict (HB). Métodos: Estudo transversal incluindo 30 indivíduos com diagnóstico médico de DPOC, segundo critérios GOLD, atendidos no Centro de Reabilitação Pulmonar do Pavilhão Pereira Filho e do ambulatório de Pneumologia, ambos do Complexo Hospitalar Santa Casa de Porto Alegre, no período de fevereiro à setembro de 2010. O gasto energético foi mensurado pela CI usando monitor específico, assim como predito pela equação de HB. Os participantes também foram submetidos à avaliação antropométrica, através dos parâmetros de peso, altura, índice de massa corporal (IMC), dobra cutânea tricipital (DCT), circunferência do braço (CB) e circunferência muscular do braço (CMB), além de aplicação da avaliação nutricional subjetiva global (ANSG), bem como verificação do consumo alimentar. Os valores encontrados foram analisados através do teste t de Student, do teste qui-quadrado de McNemar e pelo método de Bland-Altman, e expressos pela média ± desvio-padrão, com nível de significância estatística p 0,05. Resultados: Do total de 30 portadores de DPOC, 70% eram do sexo masculino com idades de 62,5 ± 11,5 anos e IMC médio de 24,2 ± 4,2kg/m². O gasto energético em repouso (GER) medido pela CI foi de 1.568 ± 234,8kcal e o estimado pela equação de HB foi de 1.312 ± 120,5kcal, com diferença estatisticamente significativa entre os dois métodos (p<0,001). Quanto ao gasto energético total (GET), o valor medido pela CI foi de 2.038 ± 305,23kcal e o predito pela equação de HB foi de 2.047 ± 188kcal, sem apresentar diferença estatística significativa (p=0,853) e demonstrando uma concordância de 96,7% entre os dois métodos. Relativo ao diagnóstico nutricional, ao considerarmos apenas o IMC, 3,3% dos participantes apresentavam desnutrição, 63,3% eutrofia, 23,3% sobrepeso e 10% obesidade enquanto que pelo agrupamento de parâmetros (IMC, DCT, CB, CMB e ANSG), 53,3% dos pacientes apresentaram desnutrição, 33,3% eutrofia, 10% sobrepeso e 3,3% obesidade. Conclusão: O GER foi subestimado pela equação de HB, não apresentando boa concordância com o medido pela CI. Quanto ao GET, os resultados foram significativamente semelhantes demonstrando boa concordância entre os dois métodos. Em relação ao estado nutricional, talvez o IMC não seja suficiente para avaliar a real condição de pacientes com DPOC. / Introduction: The energy expenditure (EE) of individuals can be determined by various methods, among which are the indirect calorimetry (IC) and the prediction equations. Objective: To compare the energy expenditure of patients with chronic obstructive pulmonary disease (COPD) measured by the IC estimate by the Harris-Benedict equation (HB). Methods: Cross sectional study including 30 individuals diagnosed with COPD according to GOLD criteria, seen in the Pulmonary Rehabilitation Center of the Pereira Filho and outpatient pulmonology, both of Santa Casa Hospital Complex of Porto Alegre in the period from February to September 2010. Energy expenditure was measured by IC using a specific monitor, as predicted by the HB equation. Participants also underwent anthropometric assessment, through the parameters of weight, height, body mass index (BMI), triceps skinfold thickness (TSF), mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC), and application subjective global nutritional assessment (SGA) and to determine food consumption. The values were analyzed using the Student t test, chi-square, McNemar and the Bland-Altman and expressed as mean + standart deviation, with statistical significance level p 0.05. Results: Of 30 patients with COPD, 70% were male, aged 62.5 ± 11.5 years and average BMI of 24.2 ± 4.2kg/m². The resting energy expenditure (REE) measured by IC was 1568 ± 234.8kcal and estimated by the HB equation was 1312 ± 120.5kcal, with a statistically significant difference between the two methods (p<0.001). As for the total energy expenditure (TEE), the value measured by ICwo methods (p <0.001). As for the total energy expenditure (TEE), the value measured by IC was 2038 ± 305.23kcal and foretold the HB equation was 2047 ± 188kcal, no statistical significant difference (p=0.853) and showed a concordance of 96,7% between the two methods. Concerning the nutritional diagnosis, we consider only the BMI, 3.3% of participants had malnutrition, 63.3% were eutrophic, 23.3% overweight and 10% were obese while the grouping of parameters (BMI, TSF, CB, CMB and SGA), 53.3% of patients suffered from malnutrion, 33.3% were eutrophic, 10% overweight and 3.3% obese. Conclusion: REE was underestimated by the HB equation, not a good agreement with that measured by IC. As for the GET, the results were significantly similar showing good agreement between the two methods. In relation to nutritional status, BMI may not be sufficient to evaluate the actual condition of patients with COPD.