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.

项目摘要/摘要（来自父母奖） 南亚人（SA）是美国增长最快的主要种族，也患有更大的2型糖尿病 （T2DM）和心血管疾病（CVD）在相对较低的体重指数（BMI）的风险中与之相比 欧洲和非洲血统。这种增加的心脏代谢风险仍然存在的机制仍然存在 不明确的。我们正在提交该研究建议，以应对NIH计划公告（PA-17-- 021）要求提出解决NIDDK疾病中健康分布的建议。心脏代谢增加 SA美国人的风险代表了一种理解和不同的风险。大多是成人的协会研究 在美国以外，SA的体内脂肪百分比较高 给予BMI比其他种族群体。在SA成年人中，这些研究发现胰岛素抵抗增加，并且 血脂异常以及改善胰岛素介导的葡萄糖处置（与内脏脂肪成反比）和 细胞函数。我们建议研究SA青年，以阐明他们的早期机械变化 增加心脏代谢风险。鉴于SA的独特脂肪分布，我们建议定义生态脂肪 在美国，SA青少年的脂肪代谢改变和细胞胰岛素分泌的沉积和测试我们将 使用尖端的创新技术，包括MRI/MRS，游离脂肪酸的数学建模（FFA） 动力学和葡萄糖启用精氨酸测试（GPA）以测量胰岛素分泌能力，方法不是 以前在SA青年时代使用。我们组建了一个经验丰富的多机构（约翰·霍普金斯， CHOP，UPENN，CNMC）和多学科团队，具有成功合作的记录，以表演 与欧洲人相比 祖先（白色）（n = 50）和类似年龄，性别和BMI％ile的非裔美国人（AA）血统（n = 50）。 aa 众所周知，个体也具有增加心脏代谢风险，但有提高内脏肥胖， 使它们成为一个独特的比较组。目的：1。检查体内与祖先有关的差异 分布（通过MRI/MRS），FFA通量（通过3小时的口服葡萄糖耐量测试和脂肪酸的最小模型 动力学），并比较祖先群体之间内脏肥胖与FFA通量之间的关系。 2。 检查细胞胰岛素分泌能力（通过GPA）的祖先相关差异，并比较 FFA通量与胰岛素分泌能力之间的关系。 3。比较CVD和T2DM 这三组之间的危险因素和血管末端器官损伤（主动脉脉冲波速度），并测试 FFA通量与心脏代谢风险概况之间关系的与祖先相关的差异。探索性 目的：比较脂肪细胞衍生的外泌体microRNA参与两组之间胰岛素信号的传导， 测量其与细胞胰岛素分泌能力的关联，以产生假设。那，这个建议 将研究依托脂肪，FFA通量和细胞分泌之间的关联是否因祖先而变化 撞击心脏代谢风险，期望这可能导致特定于祖先的治疗选择。