Magister Scientiae (Medical Bioscience) - MSc(MBS) / The incidence of non-communicable diseases is increasing worldwide, with South Africa being no exception. Non-communicable diseases are classified as non-infectious and are often referred to as lifestyle diseases as they are caused by common, modifiable risk factors such as unhealthy diet, obesity, tobacco use and lack of physical activity. Due to the increasing prevalence of childhood obesity diseases such as fatty pancreas and fatty liver are becoming more common. Cardiovascular disease, and more specifically atherosclerosis is the underlying cause in most adult deaths. Disease pathogenesis starts in childhood and can be detected via Aortic intima-media thickness (IMT). The developmental origins of health and disease hypothesis (DOHaD) proposes that exposures in-utero may result in persistent adaptations including alterations in metabolism.

OBJECTIVES: The aim of this study is to assess the association between different adiposity indices, dental development and skeletal maturation in children and adolescents. METHODS: A total of 115 patients who presented to the orthodontic clinics at Boston University were examined for their height, weight, skeletal maturation, and 10 different adiposity indices. Statistical analysis included chi-square, ANOVA, and multiple ordinal regression models. RESULTS: In the sample (59% female, 41% male) the mean age was 14 years, (SD:2.5), height 160 cm (SD:11.9), weight 61 kg (SD:19.1), and ethnicity was 31% African Americans, 31% Hispanics, 27% Caucasians, and 9% Asians. The Pearson correlation coefficient showed SMI was significantly correlated with (by order of correlation strength) CVMI (P<.01), dental development according to Demirjian (P<.01), root completion (P<.01), eruption (P<.01), fat free mass (FFM) (P<.01), total body water (TBW) (P<.01), body adiposity index (BAI) (P<.01), BMI (P<.01), fat mass (P<.01), right subscapular skinfold (P<.01), BMI percentile (P<.01), fat percentage (P<.01), right triceps skinfold (P<.01), and waist/hip ratio (P<.01). For CVMI, it was significantly correlated in order of strength with SMI (P<.01), BMI % (P<.01), dental development (Demirjian) (P<.01), root completion (P<.01), eruption (P<.01), FFM (P<.01), TBW (P<.01), BAI (P<.01), waist/hip ratio (P<.01), BMI (P<.01), fat mass (P<.01) and right subscapular skinfold (P<.01). However, the Waist/Height ratio was not significantly related with either methods of skeletal assessment. Using the Chisquare test, we found that no adiposity index was statistically significant predictor of any dental outcome (i.e., dental development by Demirjian, root completion and eruption sequence) except for dental development (Demirjian) which was statistically significantly related with the waist/hip ratio. After controlling for other covariates (i.e., age and gender) for skeletal outcomes, all adiposity indices were statistically significant predictors for SMI including BMI percentile, BMI, BAI, fat percentage, fat mass, FFM, TBW, BIA, and waist/height ratio. CONCLUSIONS: Children and adolescents with increased adiposity values (i.e., BMI percentile, BMI, BAI, fat percentage, fat mass, FFM, TBW, BIA, and waist/height ratio), had higher probability of being skeletally more mature as measured by SMI. / 2021-08-22T00:00:00Z

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18683号 / 医博第3955号 / 新制||医||1007(附属図書館) / 31616 / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 岩田 想, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

No description available.

Introduction: Survivors of childhood brain tumors (SCBT) are an emerging group of cancer survivors that has an increased risk of cardiovascular disease, stroke, and type 2 diabetes. SCBT have equivalent obesity rates but excess fat mass (adiposity) when compared to the general population. As adiposity is an important and potentially modifiable risk factor for cardiometabolic outcomes in the general population, its measurement may allow for early stratification of adverse health outcomes in SCBT so that they can be targeted with prevention and treatment strategies designed to improve outcomes. However, measuring adiposity often requires specialized equipment that is not always readily available, and a clinical measure is needed to facilitate these measurements in a feasible fashion. Tri-ponderal Mass Index (TMI; kg/m3) is a superior measure of adiposity compared to Body Mass Index (BMI) z-score in healthy children. However, it has not been assessed in SCBT. The aim of this thesis was to validate TMI as an adiposity measure in SCBT compared to non-cancer controls. Methods: A cross-sectional analysis was completed from a cohort study sample including 44 SCBT (n=20 female) and 137 (n=64 female) healthy controls between 5-17 years of age. Total adiposity was determined by fat mass percentage (%FM) using bioelectrical impedance analysis and central adiposity was assessed by waist-to-hip (WHR) and waist-to-height (WHtR) ratios. Results: TMI demonstrated equally strong correlations with total adiposity and stronger association with WHtR compared to BMI z-score in SCBT and healthy control children. Conclusions: TMI may serve as a reliable and feasible clinical measure of adiposity in both SCBT and healthy children. The availability of TMI may allow for early stratification of survivors at risk of excess adiposity to allow early targeting with interventions to improve health outcomes. / Thesis / Master of Science in Medical Sciences (MSMS) / Over the last thirty years, childhood cancer survival rates have greatly improved. However, these rates decrease over the lifespan of survivors. Certain groups within the survivors of childhood cancer population, including survivors of childhood brain tumors (SCBT), are at a higher risk of obesity, heart disease and type 2 diabetes. Excess body fat is a major contributor to the development of these adverse health outcomes in the general population and may represent an entry point to prevent and treat these conditions in SCBT. However, measuring fat mass in the clinical setting requires specialized equipment that can be expensive, time-consuming and not readily available in all settings. Therefore, this thesis aims to explore measures of fat mass that are both feasible and reliable in a clinical setting in SCBT compared to the general pediatric population. We have identified the tri-ponderal mass index (TMI), defined as weight divided by height cubed (kg/m3) as a valid measure of the fat mass in both SCBT and healthy children. We conclude that TMI may serve as a reliable and feasible measure of adiposity in both SCBT and healthy children in clinical settings and assist in the early identification of survivors at risk of obesity and cardiometabolic outcomes to prioritize early interventions to improve outcomes.

Rationale & Background: Gaining excessive adiposity in pregnancy is associated with altered cardiometabolic profile and adverse pregnancy outcomes. Lifestyle interventions may reduce excess weight gain, but the effect on fat gain is unclear. Our study explored this question by 1) comparing measures of body fat (BF) by bioelectrical impedance analysis (BIA) and 4-site skinfold thickness (SFT); 2) assessing the impact of a nutrition+exercise intervention on adiposity changes; 3) elucidating associations between adiposity changes and cardiometabolic biomarkers and adverse pregnancy outcomes. Study Design: Participants randomized to receive a high dairy protein diet and exercise program (intervention) or standard care (control) in the Be Healthy in Pregnancy RCT (NCT 01689961) had adiposity measured at 12-17, 26-28, and 36-38 weeks gestation by BIA (%BF) and SFT (sum and %BF), and at 6 months postpartum also by DXA. Fasted blood samples collected at 12-17 and 36-38 weeks gestation were analyzed for glucose, lipid profile, insulin, leptin, adiponectin, and CRP. Pregnancy outcomes were abstracted from medical charts. Results: In 181 participants, BIA %BF and SFT %BF had good agreement in early pregnancy and postpartum, but low agreement in late pregnancy. Adiposity changes across pregnancy were similar between study arms but were greater in normal weight compared to overweight women. Insulin and leptin were negatively associated with change in SFT (sum and %BF). Triglycerides were negatively associated with change in BIA %BF, while HDL was positively associated. Neither caesarean section nor operative vaginal delivery were associated with adiposity change. Conclusion: Adiposity measured by sum of SFT and BIA %BF increased across pregnancy but was not influenced by the diet+exercise intervention. Associations of adiposity change with cardiometabolic biomarkers varied between measurement tools. The lack of adiposity measurement tools appropriate across pregnancy and in clinical settings presents a concern for assessing clinical responses to adiposity change across pregnancy. / Thesis / Master of Science (MSc) / Pregnancy is associated with a natural gain in body fat, but it can reach excessive amounts. Excess body fat is of clinical consequence as it is associated with poor cardiovascular health and abnormal pregnancy outcomes. Improving diet and physical activity habits may reduce excess weight gain, but little is known about how it influences fat gained during pregnancy. In our study body fat gain during pregnancy was similar between the lifestyle intervention and control groups. However, entering pregnancy with greater BMI was associated with less fat gain during pregnancy. Changes in body fat influenced cardiovascular blood markers, but results differed between body fat assessment tools. We also found that methods to measure body fat produce different results at different stages of pregnancy. Our findings provide insight on the factors that influence fat gain during pregnancy and highlight the need for better tools to measure body fat accurately in pregnancy.

Obesity is associated with sympathetic neural activation and elevated blood pressure(1,2). However, it is unclear whether modest elevations in body weight are sufficient to induce increases sympathetic activity (3). Furthermore, there is a large amount of individual variability in the blood pressure response to weight change (4). The reason(s) for this inter-individual variability are still uncertain, but body fat distribution and cardiorespiratory fitness may play a role (5,6). To address these and other issues regarding the relation between adiposity, sympathetic neural activity and blood pressure, we first examined the effects of modest, diet-induced weight gain on muscle sympathetic nervous system activity (MSNA) in healthy, lean, normotensive individuals. We hypothesized that modest weight gain would increase MSNA in these individuals, and that this neural activation would be accompanied by increases in blood pressure. Concordant with this hypothesis, MSNA and resting blood pressure were significantly elevated following weight gain. The increase in MSNA was correlated with the magnitude of body weight and fat gain, but was not obviously related to increases in visceral fat. We next examined the ability of cardiorespiratory fitness (CRF) to modulate the weight gain-induced increase in blood pressure in the same cohort of young, nonobese and normotensive individuals. We hypothesized that the increase in blood pressure would be attenuated in individuals with higher- compared with lower CRF (HCRF and LCRF, respectively). Indeed, we found that HCRF experienced significantly smaller increases in resting and ambulatory blood pressure compared to LCRF. In the pooled sample, baseline fitness was inversely related to the changes in resting systolic and diastolic pressure, and this relation was not diminished after statistically controlling for changes in abdominal visceral fat. The results of the present investigation suggest that even modest weight gain increases sympathetic activity and blood pressure, which, if left untreated, may contribute to the development of hypertension and other cardiovascular disorders. Maintenance of higher levels of CRF during periods of weight gain may reduce cardiovascular disease risk by mitigating the increases in blood pressure. Collectively, these findings may have important implications for understanding the link between obesity and hypertension. References 1. Davy KP. The global epidemic of obesity: are we becoming more sympathetic? Curr Hypertens Rep. 2004;6:241-6. 2. Grassi G, Seravalle G, Cattaneo BM, et al. Sympathetic activation in obese normotensive subjects. Hypertension. 1995;25:560-3. 3. Huggett RJ, Scott EM, Gilbey SG, Bannister J, Mackintosh AF, Mary DA. Disparity of autonomic control in type 2 diabetes mellitus. Diabetologia. 2005;48:172-9. 4. Masuo K, Mikami H, Ogihara T, Tuck ML. Weight gain-induced blood pressure elevation. Hypertension. 2000;35:1135-40. 5. Hayashi T, Boyko EJ, Leonetti DL, et al. Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. Ann Intern Med. 2004;140:992-1000. 6. Barlow CE, LaMonte MJ, Fitzgerald SJ, Kampert JB, Perrin JL, Blair SN. Cardiorespiratory fitness is an independent predictor of hypertension incidence among initially normotensive healthy women. Am J Epidemiol. 2006;163:142-50. / Ph. D.

No description available.

Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated.We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level.

The Body Mass Index (BMI) is a tool used broadly by public health agencies to assess weight in populations. However, when differentiating between fat mass and fat free mass the formula (BMI = weight in kilograms/height in meters2) is not applicable. Research suggests that evaluating body fat percentage and adipose tissue deposition may provide a nuanced indication of overall health, making it more accurate on an individual basis. This study evaluated four methods (Body Mass Index, waist circumference, A Body Shape Index, and Waist to Stature Index) that assess body composition and their ability to predict body fat percentage in female collegiate athletes and overweight/obese females. The study also investigated if the CUN‐BAE formula could calculate body fat percentage accurately in comparison to air displacement plethysmography in both populations. The study found that the universality of these algorithms is uncertain in diverse populations and that the predictive power of anthropometric‐based formulas is inconsistent when considering body fat percentage.