• Assessing the Relationship between Adverse Childhood Experiences and Body Mass Index Trajectory of Children and Adolescents

      Park, Hyeshin; Barth, Richard P., 1952- (2017)
      Background: More than a third of American children and adolescents are overweight or obese. Because childhood obesity is a risk factor for various health, mental health, and socioeconomic problems in adulthood, health practitioners, policy makers, and researchers continue to identify growth trajectories and clarify risk factors for unhealthy growth trajectories. The purpose of this dissertation was to identify subcategories of children who follow different body mass index (BMI) trajectories, describe these groups, and explore whether adverse childhood experiences (ACEs) predict group membership. Methods: A sample of children who participated in the Longitudinal Studies on Child Abuse and Neglect (LONGSCAN) study at the Eastern site (Baltimore, MD), and whose demographic and BMI data were collected at age four, were included in the study (n=201). Latent Class Growth Analysis (LCGA) was used to examine longitudinal patterns of BMI growth over a span of 14 years (4 years - 18 years). Data were assessed and the optimal number of classes to describe the growth trajectories was selected. Bivariate and multivariate data analyses were used to describe the children in each group. Multinomial logistic regression was used to examine whether the number of cumulative preschool (age 4) or school-aged ACEs (ages 4 to 14) predicted group membership. Results: Overall, the percentage of overweight/obesity increased with each additional wave. Based on z-BMI score, at age 4, 20.1% were overweight/obese. A marked increase was identified when children were 12 years old (42.0%) and then at 18 years (49.4%). Three BMI growth trajectories were identified: expected growth, emerging overweight, and increasing obesity. Most children followed an expected growth trajectory (73.6%). However, about a fifth followed a trajectory with a steep increase in BMI over time (emerging overweight = 21.9%) and a small percentage of the children exhibited a high initial BMI as well as a high rate of increase (increasing obesity = 4.5%). Ages 8 to 12 and ages 16 to 18 had especially steep slopes when it came to BMI increase in the emerging overweight and increasing obesity trajectories. A higher preschool ACEs score was associated with a low odds ratio of being in the emerging overweight group compared to the expected growth group; school aged ACEs score did not predict membership to a particular class. Female children and those with a higher primary maternal caregiver BMI when the children were 4 years old predicted being in the emerging overweight group compared to the expected growth group. Implications: The time periods that are especially sensitive to steeper weight gain are likely to be the time periods when interventions should be targeted for children in a low income, urban, largely African American community. The current study had results that were divergent from the hypothesis in that children who had higher ACEs at age four were less likely to have an obesity-prone BMI trajectory. Reasons and implications are discussed. The child's gender and the child's maternal caregiver's weight status should provide some guidance in intervention and treatment decisions.
    • BONE MINERAL DENSITY AND HIP FRACTURE BY BODY MASS INDEX

      Lloyd, Jennifer Tower; Orwig, Denise L. (2013)
      Research on the intersection of obesity and bone-related outcome such as osteoporosis and fracture risk is of significant public health concern as older adults will represent 20% of the US population by 2030; the majority of whom will have either or both conditions. The mechanical loading of extra weight is assumed to prevent osteoporosis and risk of fracture. However, half of all hip fractures occur among overweight or obese older adults. Many cross-sectional studies, including Paper 1 of this dissertation, find a protective effect of obesity on osteoporosis. Paper 1, using linear regression models and data from the National Health and Nutrition Examination Survey (NHANES 2005-2008) for adults ages > 50 (n=3,296) found every unit increase in body mass index (BMI) was associated with a 0.0082 g/cm2 increase in bone mineral density (BMD). However, Paper 2 of this dissertation using longitudinal data shows that obese older adults lose more bone density over time. Using multivariable generalized estimating equations and 10 years of data from 2,570 older adults in the Health, Aging, and Body Composition Study found that obese older adults lost 0.002 g/cm2 of femoral neck BMD per year more compared with normal weight older adults (p<0.001). Prior literature on obesity and risk of fracture is mixed, although the majority of studies, as well as Paper 3, find obesity to be protective against hip fracture risk. Cox proportional hazard models and data from 2,790 U.S. older adults in NHANES III linked to Medicare claims data (1991-2007) revealed obese older adults had a 15% lower risk of hip fracture (HR=0.85, 95% CI: 0.76, 0.96) while overweight older adults had the same risk level (HR=0.94, 95% CI: 0.85, 1.04) compared to normal weight older adults. The main strength of this dissertation was the comprehensive examination of obesity and bone-related outcomes using large diverse samples of older adults and multiple statistical methods. Future research should consider other measures of body composition and bone strength. Understanding the complex relationship between body mass, bone mass, and risk of fracture is pertinent, particularly as the majority of older adults are either overweight or obese.
    • Determinants of Intrathoracic Adipose Tissue Volume and its Association with Cardiovascular Disease Risk Factors

      Liu, Xinggang; Mitchell, Braxton D. (2012)
      Background: The volume of intrathoracic fat has been associated in some studies with cardiovascular diseases risk factors. To further assess the role of intrathoracic fat in coronary atherosclerosis risk, we measured the volume of intrathoracic fat in 910 relatively healthy Amish adults from Lancaster County, PA, and assessed correlations of intrathoracic fat volume and its two subcomponents with cardiovascular risk factors and coronary artery calcification (CAC). Further we also explored the heritability and genetic determinants of intrathoracic fat volume. Methods and results: Intrathoracic fat, epicardial and pericardial fat volume were measured from EBCT scans (3-mm thickness) obtained from the right pulmonary artery to the diaphragm. There was high correlation between epicardial, pericardial and intrathoracic fat volume. Similar findings were observed while examine intrathoracic, epicardial and pericardial fat volume. Epicardial fat volume was significantly correlated with older age (p<0.001), male gender (p<0.01), and increasing BMI (p<0.001). Multivariate regression model was used to evaluate the correlation between epicardial fat volume and cardiovascular disease risk factors while adjusting for age, gender, family structure and BMI. Epicardial fat volume was associated with higher systolic (p<0.01) and diastolic (p=0.04) blood pressure, higher pulse pressure (p=0.02), higher levels of fasting glucose, insulin, triglycerides (p<0.001) and total cholesterol (p=0.05). After adjusting for BMI or waist circumference, the above associations were diminished and no longer statistically significant. Neither coronary calcification score nor coronary calcification presence (coronary calcification score>0) was associated with increased epicardial fat volume after adjusting for age and gender. Similar associations were found examining pericardial and intrathoracic fat volume. Genetic analysis revealed that intrathoracic fat shares both environmental and genetic determinants with other obesity traits. Our genome wide association analysis and targeted SNPs analysis identified several candidate SNPs/genes which might be specifically associated with this regional fat deposit. Conclusions: We conclude that intrathoracic fat volume is significantly correlated with adverse cardiovascular risk factors (although not with increased CAC) in age and gender adjusted models. However, the associations were not independent of BMI. Intrathoracic fat volume closely correlates with various obesity measurements, except liver fat, by sharing both similar environmental and genetic influences.
    • Glucose 6-Phosphate Dehydrogenase, Macronutrient Intake, and Heart Failure

      Hecker, Peter A.; Stanley, William C., Ph.D. (2012)
      Glucose 6-phosphate dehydrogenase (G6PD) catalyzes the conversion of G6P to 6-phosphogluconolactone and formation of NADPH. Human G6PD deficiency is very common, and may affect the development of metabolic abnormalities and heart failure through its affects on reactive oxygen species (ROS). NADPH fuels antioxidant pathways, but also fuels oxidant production by NADPH oxidase, uncoupled nitric oxide synthase, and other enzymes. Evidence suggests that high sugar intake, obesity, and heart failure increase [NADPH] and ROS formation, possibly by increasing the flux of glucose through G6PD. Therefore the goal of this project was to determine whether G6PD deficiency protects against or exacerbates oxidative stress and cardiac dysfunction in the context of obesity, high sugar intake, and heart failure. First, we found that G6PD deficiency decreased obesity but not metabolic abnormalities after long term dietary treatment. Second, G6PD deficiency moderately exacerbated redox stress and heart failure mediated by myocardial infarction, severe pressure overload, or mild pressure overload with high fructose intake. Third, although high sugar intake increased superoxide production, this did not correspond with increases in [NADPH] or mortality in a genetic model of cardiomyopathy. The results indicate that G6PD deficiency moderately exacerbates oxidative stress, diet-induced metabolic dysfunction, and heart failure.
    • Identification of the Exocrine Pancreas Proteases as Novel Regulators of β-cell Production

      Hostelley, Timothy Lain; Zaghloul, Norann A.
      The rising rate of type 2 diabetes (T2D) has made it a major health burden. This can largely be attributed to high rates of obesity, one of the greatest contributing factors towards the development of T2D. Despite this, the majority of obese individuals are not diabetic. This raises the question of what mechanisms mediate differential susceptibility to T2D in the presence of obesity. This project seeks to address this question by studying the mechanisms of differential susceptibility to T2D in two rare obesity ciliopathies, Alström Syndrome (AS) and Bardet-Biedl Syndrome (BBS). Both of these ciliopathies are characterized by near-complete penetrance of early onset obesity, but they exhibit markedly different rates of T2D. AS patients are far more susceptible, with the majority developing T2D by age 20, compared to a much smaller subset of BBS patients that are afflicted. In light of the likely contribution of β-cells to T2D susceptibility, we set to identify mechanisms of β-cell production in them. Here we have shown β-cell loss in AS and increase in BBS as a likely contributor towards the discrepant rate of T2D. Next, RNA-Sequencing of these models identified several exocrine pancreas proteases that were differentially expressed between AS and BBS. Thus, we hypothesized that these proteases affect endocrine pancreas function. To test this, we overexpressed each protease in transgenic zebrafish embryos in which β-cells can be visualized. Overexpression significantly increased the β-cell number and rescued the loss of β-cells observed in animals depleted of alms1. We found ctrb1 overexpression led to increased β-cell proliferation in transgenic larvae and rescued the AS model reduction in proliferation. In addition, we found that the proteases are taken up by β-cells in vitro and induce proliferation in cultured β-cells and freshly isolated ex vivo islet cultures, suggesting this effect is conserved in mammalian systems. Finally, endogenous uptake of CTRB1 was found in both zebrafish and mouse models, suggesting a direct interaction between the exocrine and endocrine pancreas. These data support an important role for exocrine pancreatic enzymes in the modulation of β-cells in diabetes.
    • Mesothelial cell expression of omentin, both a target and a modulator of chronic inflammation

      Erwin, Sharis Ashley-Evette; McLenithan, John C. (2013)
      Omentin is a GPI-anchored 38-kDa secreted insulin-sensitizing glycoprotein that is expressed in the mesothelial cells of the stromal vascular fraction (SVF) of visceral adipose tissue. Mesothelial cells expressing omentin are part of the innate immune system and can contribute to the inflammatory state of visceral adipose tissue. Therefore, it is important to determine the role that omentin plays in the regulation of chronic inflammation. Primary cultures of human adipocyte mesothelial cells were isolated by biopsy trypsinization and Immunofluorescence microscopy was used to determine the purity of primary HAMC cultures. To determine if chronic inflammation is the cause of decreased omentin expression in obesity, HAMCs were treated with TNF-alpha, a pro-inflammatory cytokine, for 24 hours to simulate chronic exposure. Omentin gene expression was down-regulated by TNF-alpha significantly (39% decrease) in serum-free chronic conditions. The protein expression of omentin was also significantly decreased (31%) in serum containing conditions. To demonstrate that omentin's insulin-sensitizing activity may be mediated by anti-inflammatory actions, inflammation-dependent NF-kB luciferase reporter assays were performed in 3T3-L1 adipocytes and human adipose mesothelial cells treated with omentin and/or TNF-alpha. Omentin decreased pro-inflammatory gene transcription in 3T3-L1 adipocytes (85% decrease) and in HAMCs (68% decrease). In order to ascertain the role that omentin plays in the regulation cytokine secretion and what would result if omentin were not present, lentivirus containing omentin-specific shRNAs were generated. A complete knockdown was not achieved, but stimulation with LPS significantly increased (1.73%) the amount of TNF-alpha secretion in mesothelial cells suggesting that even partially reduced omentin protein expression can have a profound impact on the mesothelial inflammatory response. In conclusion, omentin plays a role in the anti-inflammatory response, but can also be negatively regulated by excessive and chronic pro-inflammatory cytokines.
    • Nurses' Working Conditions and Obesity

      Han, Kihye; Trinkoff, Alison M. (2011)
      Background: Job stress and shift work are known risk factors for obesity, yet comprehensive measures of job stress/work schedules (JS/WS) in relation to nurse obesity have been little investigated. Moreover, the effect of JS on obesity can vary with WS characteristics because WS comprehensively influence workers' lives. Nonetheless, there are knowledge gaps about differences in factors which are associated with nurse obesity by WS status. Purpose: This study aimed to 1) examine the proportion of overweight/obesity (OW/OB) among nurses, 2) investigate the relationship between JS/WS and nurse obesity, and 3) compare the relationship between JS and nurse obesity by WS status. Methods: The conceptual framework was based on the Demand-Control-Support model which assumes workers' health is affected by stress-producing factors in employment settings. This study was a cross-sectional secondary data analysis of 2,103 female nurses. Obesity was measured using body mass index estimates. To examine associations of JS/WS with nurse obesity, binomial logistic regression models for OW/OB incorporated independent components of JS/WS. To compare associations between JS and nurse obesity by WS status, binomial regression models were stratified by WS status (favorable WS and unfavorable WS). All models included demographics, depressive symptoms, and health and family related covariates. Results: The prevalence of OW/OB was 55%. In the overall nurse sample, longer work hours (OR=1.22, 95% CI=1.08-1.39) and jobs with lower physical exertion (OR=0.83, 95% CI=0.73-0.95) and more limited movement (OR=1.14, 95% CI=1.02-1.28) were significantly associated with OW/OB. When comparing associations between JS and nurse obesity by WS status, among nurses with favorable WS, OW/OB nurses reported significantly less supervisory support (OR=0.83, 95% CI=0.68-1.00). On the other hand, among those with unfavorable WS, no job stress components were significantly related to OW/OB. Only healthy behaviors (i.e., exercise and sleep) were significantly associated with decreased odds of OW/OB (OR=0.79, 95% CI=0.66-0.95). Conclusion: Organizational supports to limit adverse WS are needed. In particular, for nurses with unfavorable WS, educational interventions about sleep hygiene and other lifestyle modifications for adaptation to their WS may help improve health. For nurses with favorable WS, organizational supports for alleviating nurses' home/family responsibilities and stress are needed.
    • Participation and Effectiveness of Worksite Health Promotion Program

      Han, Myeunghee; Doran, Kelly; Storr, Carla L. (2019)
      Background: Worksite Health Promotion Programs (WHPPs) are limited by low participation and engagement. However, little is known about what factors influence participation and the relationship between participation and changes in body weight and composition. Mobile health technology (mHealth) may facilitate participation and engagement in WHPPs as mhealth is not limited by time or location, which are known barriers to participation and engagement. Yet, few studies have examined the use and effectiveness of WHPPs using mHealth interventions that aimed to change body weight and composition. Purpose: To explore the features and effectiveness of WHPPs in previous studies that used mHealth interventions. To identify factors influencing participation and engagement in a WHPP and the relationship between participation and changes in body weight and composition. Methods: A systematic literature review was conducted to explore features of WHPPs using mHealth that aimed to change body weight and composition. A secondary data analysis was conducted using data obtained from participants in the intervention group of a WHPP to identify: 1) factors that influence participation and engagement and 2) the relationship between participation and body weight and composition changes. Results: From the systematic review, 10 out of 12 WHPP studies using mHealth significantly improved body weight and composition. The most commonly used mHealth interventions were providing information, goal setting, and data entry. Based on the secondary data analysis, low levels of stress, anxiety, or high job satisfaction were significantly related to high participation in a WHPP. Significant relationships between participation and body weight and composition changes were not found due to a small sample size. However, this study found that those who reduced five pounds of body weight at six months among overweight or obese participants showed high participation in physical activity and/or diet components of a WHPP. Conclusions: WHPPs using mHealth can significantly improve body weight and composition. Employees’ psychological factors should be considered to increase participation in WHPPs. Further studies with larger sample size are needed to identify the relationship between participation and changes in body weight or body composition.
    • Race and socioeconomic status as predictors of utilization and need for total knee arthroplasty for knee osteoarthritis: Data from the OsteoArthritis Initiative study

      O'Connor, Shannon Leigh; Hochberg, Marc C.; 0000-0003-0817-258X (2016)
      Objective: Previous studies consistently report reduced rates of utilization of total knee arthroplasty (TKA) among black U.S. adults as compared with whites. This study assessed whether differences in TKA utilization rates between blacks and whites persist after including estimates of socioeconomic status and theoretical candidacy for joint replacement surgery. This study also examined whether blacks and whites differ in rate of reaching candidacy for TKA, and whether socioeconomic factors are related to reaching VTKA. Methods: This study employed data from the OsteoArthritis Initiative study. Study participants were black and white adults enrolled in the OAI study between the ages of 49 and 79 at baseline. Study aims were achieved using a discrete survival approach. Cox-analogue proportional hazards models were employed using a log minus log link to produce hazard ratios specific to respective intervals between time points. Models were fit using General Estimating Equations. Results: Results showed that blacks were significantly less likely to undergo total knee arthroplasty than whites, even after including estimates of baseline differences in BMI and number of comorbidities, baseline need for TKA, and socioeconomic status (education and income) (e^(β)=0.50, p=0.0016). Individuals who met need for TKA criteria at baseline were significantly more likely to undergoing TKA than those who did not (e^(β)=8.25, p<0.0001). Results also revealed race not to be a significant predictor of reaching need for TKA after including estimates of baseline differences in BMI and number of comorbidities. These findings persisted even with the inclusion of socioeconomic variables. Conclusions: Findings confirmed that substantial racial differences in utilization of TKA exist. The inclusion of socioeconomic status measures accounted for only a small proportion of the difference between blacks and whites in terms of TKA utilization (e^(β)=0.41 versus e^(β)=0.50). Racial differences in progression of knee OA to virtual TKA were also found, although race became non-significant after accounting for baseline differences in BMI categories (overweight and obese). Results suggest that other factors not captured in this study differentially influence the rate of TKA utilization among black and white U.S. adults.
    • Risk of Being Overweight or Obese among Army Spouses: The Impact of Deployment, Distress, and Perceived Social Support

      Fish, Tammy Lynne; Harrington, Donna (2013)
      More than half of spouses of U. S. Army active duty soldiers are overweight or obese. In the U.S. almost a half million people die annually because of health related problems to being overweight or obese (Robbins, Chao, Baumgartner, Runyan, Oordt, & Foneseca, 2006). The military spends $1.1 billion a year on problems related to being overweight or obese for active duty military personnel, retirees, and their families (Dall et al., 2007). Method: Permission was granted from the Department of Defense (DoD) and the University of Maryland Institutional Review Board (IRB) to use the 2008 Active Duty Spouses Survey (ADSS) for the secondary data analyses used in this dissertation. Multiple and logistic regression analyses of U.S. Army spouses (n = 1863) examine the association of deployment status within the last year (not deployed, deployed but not to a combat zone, and deployed to a combat zone) with weight status, as measured with body mass index (BMI) scores (healthy weight versus overweight or obese). The independent variables examined were gender, age, race, rank of soldier, education, psychological distress, and perceived social support scores. Results: Deployment status and weight status were not related (p = .097). Three-quarters of the male spouses and almost half of the female spouses were overweight or obese. Spouses of soldiers in the enlisted ranks (E5-E9), minority spouses, and those without at least a four-year college degree are more likely to be overweight or obese. As spouses' age and psychological distress increases and perceived social support decreases their BMI increases. Conclusions: Findings suggest the risk factors associated with being overweight or obese are minorities; male spouses; the ranks of E5 - E9; less than a four-year degree; as age and psychological distress scores increase so does BMI; and as perceived social support scores increase the BMI decreases. The risk factors may contribute to the Army Surgeon General's Performance Triad of sleep, activity, and nutrition and be used to assist Army personnel and Department of the Army (DA) civilians to teach spouses awareness and methods of changing behaviors that result in choosing healthy options.