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（来自家长奖） 南亚人 (SA) 是美国增长最快的主要族群，其 2 型糖尿病患病率也较高 与正常人相比，体重指数 (BMI) 相对较低的情况下 (T2DM) 和心血管疾病 (CVD) 风险 欧洲和非洲血统仍然是导致心脏代谢风险增加的机制。 我们提交此研究计划是为了响应 NIH 计划公告 (PA-17-)。 021）请求提出解决 NIDDK 疾病健康差异的建议。 南澳美国人的风险是一种尚未得到充分研究的不同风险，主要是针对成人进行的相关研究。 美国以外的地区表明，SA 的体脂百分比、内脏脂肪含量和腹部脂肪含量较高 这些研究发现，与其他种族的成年人相比，体重指数较高的南澳成年人的胰岛素抵抗和胰岛素抵抗有所增加。 血脂异常以及胰岛素介导的葡萄糖处理减少（与内脏脂肪成反比）和 我们建议研究 SA 青少年，以阐明其早期机制变化。 鉴于 SA 独特的脂肪分布，我们建议定义异位脂肪。 对美国 SA 青少年脂肪代谢和  细胞胰岛素分泌改变的沉积和测试 我们将 使用尖端的创新技术，包括 MRI/MRS、游离脂肪酸 (FFA) 的数学模型 动力学和葡萄糖强化精氨酸试验（GPA）来测量胰岛素分泌能力，方法不 我们组建了一个经验丰富的多机构（约翰·霍普金斯大学、 CHOP、UPenn、CNMC）和具有成功合作记录的多学科团队，执行 一项针对 12-21 岁南非血统青年 (n=50) 的横断面研究，与欧洲人相比，BMI ≥ 80%ile 年龄、性别和 BMI% AA 相当的白人血统 (n=50) 和非裔美国人 (AA) 血统 (n=50)。 众所周知，个体的心脏代谢风险也增加，但内脏脂肪减少， 使他们成为一个独特的比较组 目的： 1.检查与血统相关的身体脂肪差异。 分布（通过 MRI/MRS）、FFA 通量（通过 3 小时口服葡萄糖耐量试验和脂肪酸最小模型） 动力学），并比较祖先群体内脏脂肪和 FFA 通量之间的关系 2。 检查  细胞胰岛素分泌能力（按 GPA）的血统相关差异，并比较 3. 比较CVD和T2DM 比较3组之间的危险因素及血管终末器官损伤（主动脉脉搏波速度），并进行检测 FFA 通量与心脏代谢风险状况之间关系的祖先相关差异。 目的：比较各组之间参与胰岛素信号传导的脂肪细胞来源的外泌体 microRNA，以及 测量它们与  细胞胰岛素分泌能力的关联，以产生假设。 将研究异位脂肪、FFA 通量和  细胞分泌之间的关联是否因祖先而异 影响心脏代谢风险，预计这可能会导致针对血统的治疗选择。