Thesis (M.A. (Human Movement Sciences))--North-West University, Potchefstroom Campus, 2008.

Studies in both children and adults indicate that waist circumference (WC), a measure of abdominal obesity is closely related to cardiovascular risk factors. The accurate identification of abdominally obese children in health screening programmes for early intervention is of importance. There are, however, concerns about using international definitions for screening purposes because in most instances these have been derived from Western populations and, therefore, may have limited usefulness to children in other parts of the world. When these cut–off points are used in developing countries, they ignore the fact that the growth patterns of children and burdens of disease vary between countries. Due to lack of population specific cut–off points for children in the developing world it may be tempting and convenient to use the same cut–off points as for children in developed countries, but such a practice runs the risk of exporting failure. Ideally, a screening tool should have both high sensitivity and specificity, and these are important considerations in choosing the definition for the detection of childhood abdominal obesity. High sensitivity is necessary to avoid failure of identifying obese children and high specificity of the screening tool ensures that non–obese children are not misclassified as obese, which may otherwise lead to unnecessary treatment and psychosocial implications of stigmatisation. Failure to identify the abdominally obese child may have more serious consequences than misclassification, since it results in an increase in adult morbidity and mortality. Therefore, the main aim of this thesis was to examine fat distribution patterns of black South African (SA) children in relation to health risk. The specific objectives were to: compare the body composition of black stunted and non–stunted children from two rural communities in South Africa; to describe and compare the age and sex specific WC percentile distribution for black SA children from different study populations and compare the WC percentile distribution with those for African–American (A–A) children and to assess the diagnostic accuracy of waist–to–height ratio (WHtR) as a marker for high blood pressure, a cardiovascular risk factor in SA children. Findings of this study demonstrated increased total adiposity in non–stunted children, but trends of increased central adiposity, measured as WHtR in stunted children. This warrants further investigation on this relationship among children older than 13 years in the African context where many children are stunted. The differences observed between the different data sets and between SA and A–A children suggest that nationally representative data should be used to develop age, sex and ethnic specific WC percentiles for this population. The results indicate clearly that the median WC of children from SA studies is smaller than those of A–A children, with a medium to large effect size for the difference. Results also suggest concern with respect to high WC values (> 80 cm) among some children. The recommended universal WHtR cut–off value of 0.5 for assessment of cardiovascular risk is not suitable for black SA children because it had low sensitivity in predicting high blood pressure. The absence of locally developed cut–off values for WC and WHtR for children warrants research due to the associations between being overweight and obese and disease outcomes. It is fundamental to detect risk at an early stage so that appropriate intervention can be initiated timeously. / Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2011.

Whole yellow pea flour (WPF) and fractionated yellow pea flour (FPF) are novel functional food ingredients that vary in nutritional composition. Consequently, the health benefits of WPF and FPF remain undefined. The purpose of this research was to identify the effects of WPF and FPF on risk factors and morbidities associated with cardiovascular disease, diabetes and obesity as well as the gastrointestinal microbiome. Using USDA recommended dosages of WPF and FPF, clinical endpoints and the colonic microbiome were investigated using a human clinical trial engaging a cross-over design and a diet and energy controlled paradigm. Humans were also utilized to investigate post-prandial glycemic responses and sensory characteristics of novel functional foods formulated with WPF. Finally, Golden Syrian hamsters were used to assess the impact of high doses of WPF and FPF on clinical endpoints and caecal microbial abundance. Results reveal that USDA recommended dosages of WPF and FPF in humans decreased (p<0.05) fasting insulin and estimates of insulin resistance compared to white wheat flour (WF). Android-to-gynoid fat ratios in women were lower (p=0.027) in the WPF group compared to the WF group. FPF decreased (p<0.05) post-prandial energy expenditure alongside a tendency (p<0.075) to reduce carbohydrate oxidation. Novel biscotti and banana bread formulated with WPF induced low post-prandial glycemic responses which were similar to boiled whole yellow peas and significantly lower (p<0.05) than white bread. Sensory analysis of novel WPF biscotti and banana bread demonstrated that WPF-based food products are palatable and acceptable for human consumption. Hamsters consuming diets containing 10% WPF and FPF induced similar reductions (p<0.05) in fasting insulin levels compared to controls. However, animals consuming WPF increased (p<0.05) oxygen consumption while FPF decreased (p<0.05) fasting glucose levels. In addition, terminal restriction fragment length polymorphism analysis revealed that WPF and FPF induced distinct shifts in caecal microbial populations within the phyla Firmicutes. Finally, pyrosequencing analysis of human fecal microbiota demonstrated that FPF and WPF induced shifts in bacterial genera, primarily within Bacteroidetes and Firmicutes. In conclusion, whole and fractionated yellow pea flours are functional food ingredients and can be utilized to manage risk factors for lifestyle-related diseases in humans.

Thesis (M.A. (Human Movement Sciences))--North-West University, Potchefstroom Campus, 2008.

Studies in both children and adults indicate that waist circumference (WC), a measure of abdominal obesity is closely related to cardiovascular risk factors. The accurate identification of abdominally obese children in health screening programmes for early intervention is of importance. There are, however, concerns about using international definitions for screening purposes because in most instances these have been derived from Western populations and, therefore, may have limited usefulness to children in other parts of the world. When these cut–off points are used in developing countries, they ignore the fact that the growth patterns of children and burdens of disease vary between countries. Due to lack of population specific cut–off points for children in the developing world it may be tempting and convenient to use the same cut–off points as for children in developed countries, but such a practice runs the risk of exporting failure. Ideally, a screening tool should have both high sensitivity and specificity, and these are important considerations in choosing the definition for the detection of childhood abdominal obesity. High sensitivity is necessary to avoid failure of identifying obese children and high specificity of the screening tool ensures that non–obese children are not misclassified as obese, which may otherwise lead to unnecessary treatment and psychosocial implications of stigmatisation. Failure to identify the abdominally obese child may have more serious consequences than misclassification, since it results in an increase in adult morbidity and mortality. Therefore, the main aim of this thesis was to examine fat distribution patterns of black South African (SA) children in relation to health risk. The specific objectives were to: compare the body composition of black stunted and non–stunted children from two rural communities in South Africa; to describe and compare the age and sex specific WC percentile distribution for black SA children from different study populations and compare the WC percentile distribution with those for African–American (A–A) children and to assess the diagnostic accuracy of waist–to–height ratio (WHtR) as a marker for high blood pressure, a cardiovascular risk factor in SA children. Findings of this study demonstrated increased total adiposity in non–stunted children, but trends of increased central adiposity, measured as WHtR in stunted children. This warrants further investigation on this relationship among children older than 13 years in the African context where many children are stunted. The differences observed between the different data sets and between SA and A–A children suggest that nationally representative data should be used to develop age, sex and ethnic specific WC percentiles for this population. The results indicate clearly that the median WC of children from SA studies is smaller than those of A–A children, with a medium to large effect size for the difference. Results also suggest concern with respect to high WC values (> 80 cm) among some children. The recommended universal WHtR cut–off value of 0.5 for assessment of cardiovascular risk is not suitable for black SA children because it had low sensitivity in predicting high blood pressure. The absence of locally developed cut–off values for WC and WHtR for children warrants research due to the associations between being overweight and obese and disease outcomes. It is fundamental to detect risk at an early stage so that appropriate intervention can be initiated timeously. / Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2011.

Optimal pharmacotherapy requires an understanding of the dose-exposure (pharmacokinetics or PK) to response (pharmacodynamic or PD) relationship. Little is known about the influence of obesity on this dynamic system as PK studies in obesity have been largely descriptive rather than explanatory. This has led to a paucity of dosing guidelines for the obese, and arbitrary dose selection in the clinic. There is a need to quantify the impact of obesity on drug clearance (CL) to ensure that exposure is matched across patients of different body compositions, thereby improving therapeutic outcomes and minimising adverse events. The global aim of this thesis was to use prior published data and new clinical trial data to understand how body composition impacts upon drug CL and renal function, and to determine how clinical study design influences the identification of these relationships. Chapter 2 of this thesis determined if conventional body size descriptors that have been used to scale drug doses to body size were appropriate. In the clinical setting, a body size descriptor commonly used for determining dose requirements is total body weight (WT), based on the assumption that physiological function and PK parameters vary according to body size. However, dosing algorithms based on WT might be unsuitable for the obese due to their altered body composition which, if inaccurate, could ultimately lead to overdoses. Alternative body size descriptors such as body surface area and ideal body weight have been used, but are limited when extrapolated to obese patients as they do not take into account the covariates required to describe differences in body composition between individuals. In contrast, it was demonstrated that lean body weight (LBW), as derived by Janmahasatian et al, had the potential to scale CL across a wide range of body compositions. This literature review and systematic analysis of previously published obesity data led to the proposal of a hypothesis that body composition is sufficient to explain the influence of obesity on drug CL and that dosing for obese patients should be based on LBW. When conducting clinical studies, the selection of an appropriate body size descriptor for scaling doses across individuals of different body compositions can be aided by a study design that allows for the identification of parameter-covariate relationships which are transportable to the obese. Chapter 3 of this thesis quantified the probability of identifying these parameter-covariate relationships as a function of differing study designs. Demographics were generated using a multivariate lognormal covariate distribution with truncation at different WT limits under both a non-stratified and stratified design. PK data were simulated from a 1-compartment, first order input, first order elimination model with LBW as the covariate on CL, termed the ‘True Model’. The ‘False Model’ had WT as the covariate on CL. Both models were fitted to the simulated data and the preferred model was selected based on the difference in objective function values. Each design was evaluated under differing magnitudes of random effects, as well as under a D-optimal sparse sampling scheme. It was shown under a simulation platform that the use of stratification and a wide covariate range enhanced the probability of selecting the true covariate from two competing covariate models. The aforementioned findings regarding LBW and stratification were used to design a new clinical study investigating the influence of obesity on renal drug elimination pathways. This work forms Chapters 4 and 5 of this thesis. Non-obese and obese healthy volunteers were recruited using a study design stratified for LBW. These subjects were administered a combination of four renal markers for the simultaneous assessment of various renal processes. One of the renal markers was para-aminohippuric acid (PAH), which provides an estimation of renal plasma flow (RPF). A population PK model was developed for PAH, which revealed that body size alone was insufficient to explain variability in RPF across healthy individuals of a large range of body compositions, although LBW emerged as the preferred covariate (p=0.053) among the body size descriptors tested. This weak covariate effect was in contrast with prior research supporting the use of LBW in normalising the effect of obesity on glomerular filtration rate (GFR), implying that body composition could play a greater role in influencing GFR than RPF. This thesis has applied new methods to the design of drug CL studies in obesity, and offered results and future directions to maximise the information gained from such clinical studies. A better understanding of alterations in PK and physiological function arising from changes in body composition should aid in optimising dose adjustments for obese patients, which is of great importance given the increasing prevalence of obesity in today’s society.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 6 uppsatser. På omslag felaktigt: Fat mass, adipokines and clinical complications of chronic kidney disease.

Thesis (M.A.)--University of North Carolina at Chapel Hill, 2003. / Includes bibliographical references (leaves 35-38). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.A.)--University of North Carolina at Chapel Hill, 2003. / Includes bibliographical references (leaves 35-38).