Cardiometabolic Health in Adolescents of South Asian Ancestry - the CHAriSmA study

南亚血统青少年的心脏代谢健康 - CHARiSmA 研究

• 批准号: 10337807
• 负责人: SHEELA NATESH MAGGE
• 金额: $ 26.04万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-04 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10337807
• 关键词: 21 year old; Accounting; Address; Adipocytes; Administrative Supplement; Adolescent; Adolescent and Young Adult; Adolescent obesity; Adult; African; African American; Age; Arginine; Asian Americans; Bangladesh; Behavioral; Beta Cell; Bhutan; Blood Vessels; Body Composition; Body fat; Body mass index; Body measure procedure; Cardiovascular Diseases; Cell physiology; Cell secretion; Childhood diabetes; Circadian desynchrony; Clinical; Clinical Research; Collaborations; Cross-Sectional Studies; Data; Deposition; Diabetes Mellitus; Disease; Dyslipidemias; Endocrinology; Ethnic Origin; Ethnic group; Etiology; European; Fatty Acids; Fatty acid glycerol esters; Funding; Future; Generations; Glucose; Health; High Prevalence; Hour; Impairment; India; Individual; Infrastructure; Insulin; Insulin Resistance; K-Series Research Career Programs; Kinetics; Lead; Magnetic Resonance Imaging; Maldives; Measurement; Measures; Mediating; Mentorship; Metabolic; Metabolic Diseases; Methodology; Methods; MicroRNAs; Mission; Modeling; NIH Program Announcements; National Institute of Diabetes and Digestive and Kidney Diseases; Nepal; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; OGTT; Obesity; Oral; Outcome; Overweight; Pakistan; Parents; Pediatrics; Phase; Physicians; Physiologic pulse; Plant Roots; Play; Questionnaires; Request for Proposals; Research; Research Personnel; Research Proposals; Research Technics; Risk; Risk Factors; Role; Sample Size; Sampling; Scientist; Secretory Cell; Sleep; Sleep Deprivation; Sleep Wake Cycle; South Asian; Sri Lanka; Techniques; Testing; Training; United States National Institutes of Health; Visceral; Visceral fat; Youth; abdominal fat; actigraphy; base; blood glucose regulation; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; career; cohort; comparison group; diabetes risk; expectation; experience; experimental study; fatty acid metabolism; glucose disposal; glucose metabolism; glucose tolerance; health disparity; high risk; indexing; innovation; insulin secretion; insulin sensitivity; insulin signaling; lipid metabolism; mathematical model; multidisciplinary; organ injury; parent grant; response; sex; skills; sleep abnormalities; sleep health; sleep quality; training opportunity

Project Summary/Abstract (FROM PARENT AWARD) South Asians (SA), the fastest growing major ethnic group in the U.S., are also at greater type 2 diabetes (T2DM) and cardiovascular disease (CVD) risk at relatively lower body mass index (BMI) compared to those of European and African ancestry. The mechanism(s) underlying this increased cardiometabolic risk remain undefined. We are submitting this research proposal in response to an NIH program announcement (PA-17- 021) requesting proposals addressing health disparities in NIDDK diseases. The increased cardiometabolic risk in SA Americans represent an understudied and disparate risk. Mostly adult, associative studies performed outside the U.S. indicate that SA have higher % body fat, visceral adiposity, and abdominal adiposity for a given BMI than other ethnic groups. In SA adults, these studies have found increased insulin resistance and dyslipidemia as well as decreased insulin-mediated glucose disposal (inversely proportional to visceral fat) and -cell function. We propose to study SA youth, in order to elucidate early mechanistic changes underlying their increased cardiometabolic risk. Given the unique fat distribution of SA, we propose to define ectopic fat deposition and test for altered fat metabolism and -cell insulin secretion in SA adolescents in the U.S. We will use cutting-edge, innovative techniques, including MRI/MRS, mathematical modeling of free fatty acid (FFA) kinetics, and the glucose-potentiated arginine test (GPA) to measure insulin secretory capacity, methods not previously used in SA youth. We have assembled a highly experienced, multi-institutional (Johns Hopkins, CHOP, UPenn, CNMC), and multi-disciplinary team with a track record of successful collaboration, to perform a cross-sectional study of 12-21 yrs old youth of SA ancestry (n=50), BMI ≥80%ile, compared to European ancestry (White) (n=50) and African American (AA) ancestry (n=50) of comparable age, sex, and BMI%ile. AA individuals are known to also have increased cardiometabolic risk but have decreased visceral adiposity, making them a unique comparison group. Aims: 1.To examine ancestry-related differences in body fat distribution (by MRI/MRS), FFA flux (by 3-hour oral glucose tolerance test and Minimal Model of fatty acid kinetics), and to compare the relationships between visceral adiposity and FFA flux among ancestral groups. 2. To examine ancestry-related differences in -cell insulin secretory capacity (by GPA), and compare the relationship between FFA flux and insulin secretory capacity among groups. 3. To compare CVD and T2DM risk factors and vascular end organ injury (aortic pulse wave velocity) among the 3 groups, and test for ancestry-related differences in the relationships between FFA flux and cardiometabolic risk profile. Exploratory Aim: to compare adipocyte-derived exosomal microRNAs involved in insulin signaling among the groups, and measure their association with -cell insulin secretory capacity, for hypothesis generation. Thus, this proposal will investigate whether associations between ectopic fat, FFA flux, and -cell secretion vary by ancestry to impact cardiometabolic risk, with the expectation that this may lead to ancestry-specific treatment options.

项目概要/摘要（来自帕萨迪纳奖） 南亚人（SA）是美国增长最快的主要种族群体，也患有更严重的2型糖尿病 （T2 DM）和心血管疾病（CVD）风险相对较低的体重指数（BMI）相比， 欧洲和非洲血统。这种心脏代谢风险增加的潜在机制仍然存在 未定义。我们提交这项研究提案是为了响应NIH项目公告（PA-17- 2017）。 021)征求解决NIDDK疾病中健康差距的建议。心脏代谢增加 美国人的风险代表了一种研究不足和不同的风险。大多数为成人，进行了相关研究 美国以外的研究表明，SA有更高的体脂百分比，内脏脂肪和腹部脂肪， BMI比其他种族高。在SA成人中，这些研究发现胰岛素抵抗增加， 血脂异常以及胰岛素介导的葡萄糖处置减少（与内脏脂肪成反比）， 细胞功能。我们建议研究SA青年，以阐明其潜在的早期机制变化， 增加心脏代谢风险。鉴于SA独特的脂肪分布，我们建议定义异位脂肪 沉积和测试改变脂肪代谢和胰岛细胞胰岛素分泌在SA青少年在美国，我们将 使用尖端的创新技术，包括MRI/MRS，游离脂肪酸（FFA）的数学建模 动力学和葡萄糖增强精氨酸试验（GPA）测量胰岛素分泌能力，方法不 以前用在青年人身上。我们已经组建了一个经验丰富的，多机构（约翰霍普金斯， CHOP，UPenn，CNMC）和具有成功合作记录的多学科团队， 一项对12-21岁SA血统青年（n=50）的横断面研究，BMI ≥ 80% ile，与欧洲人相比， 年龄、性别和BMI百分比相似的血统（白色）（n =50）和非裔美国人（AA）（n=50）。AA 已知个体还具有增加的心脏代谢风险但具有降低的内脏肥胖， 使他们成为一个独特的对照组。研究目的：1.探讨体脂的祖先差异 分布（MRI/MRS）、FFA通量（3小时口服葡萄糖耐量试验和脂肪酸最小模型 动力学），并比较祖先群体之间内脏肥胖和FFA通量之间的关系。2. 检查胰岛细胞胰岛素分泌能力（GPA）的祖先相关差异，并比较 各组间FFA通量与胰岛素分泌能力的关系。3.比较CVD和T2 DM 危险因素和血管终末器官损伤（主动脉脉搏波速度），并测试 FFA通量和心脏代谢风险特征之间的关系存在与祖先相关的差异。探索性 目的：比较各组间脂肪细胞来源的参与胰岛素信号传导的外泌体microRNA， 测量它们与胰岛β细胞胰岛素分泌能力的关联，以产生假设。因此，本提案 将研究异位脂肪、游离脂肪酸流量和胰岛细胞分泌之间的关系是否因血统而异， 影响心脏代谢风险，并期望这可能导致祖先特异性治疗选择。