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: 9980384
• 负责人: SHEELA NATESH MAGGE
• 金额: $ 67.36万
• 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/9980384
• 关键词: 21 year old; Address; Adipocytes; Adolescent; Adolescent and Young Adult; Adult; Affect; African; African American; Age; Arginine; Asian Americans; Bangladesh; Beta Cell; Bhutan; Blood Vessels; Body Composition; Body fat; Body mass index; Cardiovascular Diseases; Cell physiology; Cell secretion; Collaborations; Cross-Sectional Studies; Data; Deposition; Disease; Dyslipidemias; Environmental Exposure; Ethnic Origin; Ethnic group; European; Fatty Acids; Fatty acid glycerol esters; Free Association; Future; Generations; Glucose; Health; Hour; India; Individual; Inflammation; Insulin; Insulin Resistance; Investigation; Kinetics; Lead; Lipids; Lipoproteins; Magnetic Resonance Imaging; Maldives; Measures; Mediating; Metabolic; Metabolic Diseases; Methods; MicroRNAs; Modeling; NIH Program Announcements; National Institute of Diabetes and Digestive and Kidney Diseases; Nepal; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; OGTT; Obesity; Pakistan; Pathology; Pathway interactions; Pattern; Physiologic pulse; Plant Roots; Population; Request for Proposals; Research Proposals; Risk; Risk Factors; South American; South Asian; Sri Lanka; Techniques; Testing; United States National Institutes of Health; Visceral; Visceral fat; abdominal fat; adipokines; base; cardiometabolic risk; cardiometabolism; cardiorespiratory fitness; cardiovascular disorder risk; clinical phenotype; comparison group; expectation; experience; fatty acid metabolism; glucose disposal; glucose tolerance; health disparity; inflammatory marker; innovation; insight; insulin regulation; insulin secretion; insulin signaling; lipid metabolism; mathematical model; multidisciplinary; novel; organ injury; particle; response; sex

Project Summary/Abstract 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. These studies have also found increased insulin resistance and dyslipidemia as well as decreased insulin-mediated glucose disposal (inversely proportional to visceral fat) and β-cell function in SA adults. We propose to study SA adolescents, 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 β-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 adolescents. We have assembled a highly experienced, multi-institutional (CNMC, CHOP, NIH), and multi-disciplinary team with a track record of successful collaboration, to perform a cross-sectional study of 12-21 year old adolescents and young adults of SA ancestry (n=50), BMI ≥ 85%ile, compared to adolescents of 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 β-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 three 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 β-cell insulin secretory capacity, for hypothesis generation. Thus, this proposal will investigate whether associations between ectopic fat, FFA flux, and β-cell secretion vary by ancestry to impact cardiometabolic risk, with the expectation that this may eventually lead to ancestry-specific treatment options.

项目摘要/摘要 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 与欧洲和非洲相比 祖先。 研究提案应对NIH计划公告（PA-17-021），要求解决健康健康的建议 NIDDK疾病的差异。 不同的风险。 这些研究也发现。 胰岛素耐药性和血脂异常增加，因为糖氧化葡萄糖处置（偶然） 与内脏脂肪成比例）和SA成人的β细胞功能。 早期的机械变化是增加心脏代谢风险增加的基础。 建议定义异位脂肪沉积并测试SA青少年中脂肪代谢改变和β-细胞蛋白分泌的改变 在美国，我们将使用尖端的创新技术，包括MRI/MRS，脂肪脂肪的数学建模 酸（FFA）动力学和葡萄糖启用的Argine检测（GPA）以测量胰岛素分泌能力，方法不是 在SA青少年中使用的先前。 以及具有成功合作的往绩记录的多学科团队，进行12-21的横断面研究 与欧洲的青少年相比 祖先（白色）（n = 50）和类似年龄的非裔美国人（aa）血统（n = 50）和bmi％ilee。 众所周知，HABE也增加了心脏代谢风险，但Habe的内脏脂肪症减少，使主题成为 唯一比较组。 通量（通过3小时的口服葡萄糖耐量测试和最小的脂肪酸动力学模型），并比较关系 在祖先之间的内脏肥胖和通量之间。 胰岛素分泌能力（由GPA），并比较FFA通量与胰岛素分泌能力之间的关系 在3中。 在通量与祖先相关的关系差异的最差异之中 心脏代谢风险概况。 两组之间的信号传导，并测量其与细胞胰岛素分泌能力的关联 因此，该提案将研究异位脂肪，FFA和β细胞分泌之间的关联 因祖先而有所不同，以影响心脏多代表型风险，而经验导致特定于祖先的风险 治疗选择。