Location: Children's Nutrition Research Center2021 Annual Report
Objective 1: Investigate the effect of adiposity, adipokine dysregulation (the balance of circulating anti-inflammatory vs. proinflammatory factors), insulin resistance and vitamin D concentrations on bone microarchitecture (cortical porosity, trabecular thickness), bone biomarkers and endothelial function in youth with and without abnormalities in glucose metabolism. Objective 2: Evaluate the effect of high dose vitamin D therapy in a 6-month randomized controlled trial design on change in bone microarchitecture, restoration of bone biomarkers balance and endothelial function in youth. Objective 3: In two groups of 5-year old boys and girls who are either habitual consumers or non-consumers of milk and dairy (M&D) foods, we will determine anthropometry and body composition, total dietary energy intake, total energy expenditure, energy balance, biomarkers of cardiovascular health and early risk factors for Type 2 diabetes. Repeat these measurements every year for 4 years until the children are 10 years old.
The long-term objective of this project is to provide an enhanced understanding of how altered bone metabolism in the childhood years contributes to long-term skeletal health and may play a role in glucose metabolism and cardiovascular health in obese children by examining the evolution of risk factors and biomarkers of bone health early in the course of obesity and type 2 diabetes (T2DM). Specifically, we will investigate the effect of adiposity, adipokine dysregulation, insulin resistance and vitamin D concentrations on bone microarchitecture, bone biomarkers and vascular health in youth with and without abnormalities in glucose metabolism. Given the importance of vitamin D to bone mineralization and a host of metabolic functions, we will also examine whether restoration of vitamin D sufficiency, in a randomized placebo controlled study design, has a positive effect on bone microarchitecture, bone biomarkers and endothelial function. Finally, milk and dairy (M&D) products made from milk, except butter foods are the most important food groups for young children’s growth and development, and bone health. Yet, their use as a healthy food for children has been questioned because of the belief that their high fat content may contribute to excessive weight gain. Another objective of this project aims to investigate the effect of habitual M&D foods’ consumption on energy balance and whether they also have a protective effect against early cardiovascular and metabolic diseases. Overall this project will provide an enhanced understanding of how altered bone metabolism may contribute to long-term skeletal health and play a role in glucose metabolism and cardiovascular health in obese children. It will also provide evidence that habitually consuming M&D foods protect children against obesity and cardiometabolic disease.
The goal of Objective 1 is to investigate the effect of adiposity, adipokine dysregulation, insulin resistance and vitamin D concentrations on bone microarchitecture, bone biomarkers and endothelial function in youth with and without abnormalities in glucose metabolism. Despite the difficulties related to the COVID-19 pandemic, we restarted our research activities and successfully enrolled and studied participants. So far, we have enrolled 17 youth in the study. Although we restricted the study protocol to outpatient procedures, we have made progress in studying bone metabolism. We evaluated areal bone mineral density (aBMD), bone mineral content (BMC), and body composition using dual energy X-ray absorptiometry (DXA) scan. We also evaluated bone morphology measures using the high resolution peripheral quantitative compute tomography (HRpQCT) in youth. We analyzed data on a subset of participants with type 2 diabetes (n=2) compared with youth with obesity and normal glucose tolerance (n=3). The two groups had similar age, Tanner stage and adiposity measures. In these early data, we observed no difference in aBMD between youth with obesity and normal glucose tolerance compared with youth with type 2 diabetes. However, the youth with type 2 diabetes had lower BMC. We also made progress in obtaining HRpQCT scans in children and in analyzing HRpQCT microarchitecture data. The early data on this limited number of scans indicated lower tibia BMD and greater porosity at the outer 10% of the cortical bone in youth with type 2 diabetes vs. controls. This is concerning for an adverse effect of type 2 diabetes on bone health in adolescents, consistent with other hypothesis. The goal of Objective 2 is to evaluate the effect of high dose vitamin D therapy in a 6-month randomized controlled trial design on change in bone microarchitecture, restoration of bone biomarkers balance and endothelial function in youth. Recruitment of subjects into a longitudinal arm of the study could not be started due to COVID-19 restrictions, however, we hope to make progress in recruitment next year. The goal of Objective 3 is to determine anthropometry and body composition, total dietary energy intake, total energy expenditure, energy balance, biomarkers of cardiovascular health, and early risk factors for Type 2 diabetes in youth.
1. The effect of cardiorespiratory fitness and insulin resistance on bone health in Hispanic children. Obesity appears to have a negative impact on pediatric bone health, and insulin resistance may mediate this relationship. It remained unclear if cardiorespiratory fitness has a protective effect on bone in obese children thus, researchers in Houston, Texas, examined the effect of insulin resistance and cardiorespiratory fitness on bone health and found that lean body mass is the major determinant of bone mineral content and bone mineral density in pubertal Hispanic youth. Increased body fat and insulin resistance were negatively related to bone mineral content. Cardiorespiratory fitness contributed positively to the measures of bone mineral content and density. This suggests that greater cardiorespiratory fitness and higher lean mass may reduce the adverse effects of adiposity and insulin resistance on bone health in children. This supports the importance of promoting physical activity to prevent the negative impact of obesity on bone health in children.
2. Metabolic flexibility across the spectrum of glycemic regulation in youth. Metabolic flexibility (MF) refers to the ability to utilize different nutrients (fats and sugars) and to transition between them while fasting and after a meal. Impairment in metabolic flexibility can lead to metabolic disease. However, it is not clear whether metabolic flexibility is impaired in obese youth, or who is at risk. Researchers in Houston, Texas, found that adolescents with prediabetes and type 2 diabetes have a defect in metabolic flexibility. Individuals with prediabetes and type 2 diabetes can’t change the use of fuels as easily as normal weight individuals or individuals with obesity but with normal sugar levels. This is related to their severe insulin resistance which impairs the use of available fuels appropriately. Additional studies are needed to investigate which changes in diet or physical activity could improve how the body utilizes these nutrients.
3. The relationship of sleep duration and quality to energy expenditure and physical activity in children. Multiple studies have found an association between short sleep duration and obesity in children and adolescents; however, the mechanisms underlying the relationship between sleep and the risk for obesity in children are unclear. One mechanism may be through changes in energy metabolism and physical activity. Researchers in Houston, Texas, investigated the relationship of various sleep parameters (sleep duration and quality) to energy metabolism and physical activity in children and adolescents aged 5-18 years. Researchers measured the child/adolescent's body composition, and basal metabolic rate in a room calorimeter that measures how much energy is expended by the individual, and sleep and physical activity parameters during a school break. The scientists found that children and adolescents do not consistently meet the age-recommended sleep duration during school breaks. Importantly, shorter sleep duration was associated with lower basal metabolic rate which indicates that insufficient sleep duration and late sleep timing may lead to increased weight gain over time by interfering with physical activity and energy metabolism. This supports the importance of sleep hygiene with appropriate timing and adequate duration in promoting an active lifestyle and minimizing sedentary behaviors to prevent childhood obesity.