Cardiometabolic Risk Factors and Obesity in Adolescents with Down Syndrome

描述（由申请人提供）：生活在美国的超过40万人患有唐氏综合症，这是一种先天性疾病，由21号染色体的三个副本而不是两个副本引起。唐氏综合症患者的预期寿命为60岁，他们需要预防性的、循证的、针对唐氏综合症特有需求的卫生保健。肥胖和甲状腺疾病的风险增加归因于唐氏综合征，但这些问题与心血管和代谢（心脏代谢）风险、身体形象和生活质量的相关性及其管理尚未得到充分探讨。事实上，唐氏综合症患者长期以来一直被认为不会患心血管疾病。不幸的是，医学界可能已经陷入了一种错误的安全感，因为最近的证据表明，患有唐氏综合症的人实际上患心血管疾病的风险更高。由于许多成人疾病起源于儿童时期，因此审查儿童和青少年时期的风险和可能的干预措施是预防的关键。此外，与其他智力残疾患者一样，患有唐氏综合症的青少年可能存在身体、医疗和发育问题，这些问题对传统治疗模式构成挑战，并损害生活质量和身体形象。该项目的总体目标是更好地了解肥胖和甲状腺功能障碍及其治疗对唐氏综合征青少年长期心脏代谢风险的影响。本研究也希望拓宽对这些青少年的生活质量、身体形象和生活方式（身体活动和饮食模式）的理解。目的：1)比较青春期前和青少年唐氏综合征患者，以及年龄、性别、种族、民族和BMI-Z评分匹配对照组的体重指数与肥胖（通过DXA测量）、心脏代谢危险因素（非高密度脂蛋白胆固醇、脂蛋白亚类颗粒、血压、胰岛素抵抗、葡萄糖耐量、炎症标志物和脂肪因子）和动脉硬度（心血管终末器官损伤的标志物）之间的关系。2)探讨甲状腺素替代对青春期前及青少年唐氏综合征合并亚临床甲状腺功能减退患者体重指数、脂肪量、心脏代谢危险因素及生活质量（QOL）的影响。研究肥胖、生活方式（身体活动、营养）、身体形象和退行性痴呆儿童生活质量之间的关系，并探讨退行性痴呆儿童维持健康体重的障碍。这些研究通过为心血管和代谢筛查和管理指南提供科学证据，努力改善患有唐氏综合征的儿童和成人的医疗保健。

DESCRIPTION (provided by applicant): More than 400,000 people living in the US have Down syndrome, a congenital disorder arising from the presence of three, rather than two, copies of chromosome 21. With a life expectancy of 60 years, individuals with Down syndrome are in need of health care that is preventative, evidence-based, and addresses the needs unique to Down syndrome. Increased risks of obesity and thyroid disease have been ascribed to Down syndrome, but the relevance of these issues to cardiovascular and metabolic (cardiometabolic) risk, body image, and quality of life, and their management have not been fully explored. In fact, individuals with Down syndrome have long been considered protected from cardiovascular disease. Unfortunately, the medical community may have been lulled into a false sense of security as more recent evidence suggests that individuals with Down syndrome are actually at increased risk for cardiovascular disease. Because many adult diseases have origins in childhood, examining risks and potential interventions in childhood and adolescence is the key to prevention. Moreover, adolescents with Down syndrome, like others with intellectual disabilities, may have physical, medical, and developmental issues that challenge traditional treatment paradigms and compromise quality of life and body image. The overall objective of this project is to provide a better understanding of the impact of obesity and thyroid dysfunction and their treatments on long-term cardiometabolic risk in adolescents with Down syndrome. This study also hopes to broaden the understanding of quality of life, body image and lifestyle (physical activity and dietary patterns) in these adolescents. Aims: 1) To compare the relationship between body mass index and adiposity (measured by DXA), and cardiometabolic risk factors (non-HDL cholesterol, lipoprotein subclass particles, blood pressure, insulin resistance, glucose tolerance, inflammatory markers, and adipokines) and arterial stiffness (a marker of cardiovascular end organ injury) in pre-adolescents and adolescents with Down syndrome, and in age-, sex-, race-, ethnicity- and BMI-Z score- matched controls. 2) To determine the effect of thyroxine replacement on body mass index, fat mass, cardiometabolic risk factors, and quality of life (QOL) in pre-adolescents and adolescents with Down syndrome and subclinical hypothyroidism. Secondary Aim) To examine the relationship between obesity, lifestyle (physical activity, nutrition), body image, and quality of life in DS, and to explore bariers to maintaining a healthy weight in children with DS.. These studies strive to improve the health care of children and adults with Down syndrome by providing scientific evidence on which to base cardiovascular and metabolic screening and management guidelines.