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: 10428356
• 负责人: SHEELA NATESH MAGGE
• 金额: $ 90.18万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428356
• 关键词: 21 year old; Address; Adipocytes; Adolescent; Adolescent and Young Adult; Adult; Affect; African American; African American population; African ancestry; Age; Arginine; Asian Americans; Asian ancestry; 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.

项目概要/摘要 南亚人 (SA) 是美国增长最快的主要种族群体，2 型糖尿病 (T2DM) 和 与欧洲和非洲人相比，体重指数 (BMI) 相对较低的心血管疾病 (CVD) 风险 这种心脏代谢风险增加的机制仍不清楚。 响应 NIH 计划公告 (PA-17-021) 的研究提案，要求提出解决健康问题的提案 南澳美国人心脏代谢风险增加是一个尚未得到充分研究和研究的问题。 在美国以外进行的大多数成人相关研究表明，SA 的体脂百分比较高， 这些研究还发现，对于给定的体重指数，内脏肥胖和腹部肥胖高于其他种族。 胰岛素抵抗和血脂异常增加，以及胰岛素介导的葡萄糖处理减少（反之 与内脏脂肪成正比）和 SA 成人的 β 细胞功能 我们建议研究 SA 青少年，以阐明这一点。 鉴于 SA 独特的脂肪分布，我们发现其心脏代谢风险增加的早期机制变化。 提议定义异位脂肪沉积并测试 SA 青少年脂肪代谢和 β 细胞胰岛素分泌的改变 在美国，我们将使用尖端的创新技术，包括 MRI/MRS、游离脂肪的数学模型 酸（FFA）动力学，以及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（CNMC、CHOP、NIH）， 和具有成功合作记录的多学科团队，对 12-21 进行横断面研究 与欧洲青少年相比，南非血统的 2 岁青少年和年轻人 (n=50)，BMI ≥ 85%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 独特的比较组： 1. 检查体脂肪分布的血统相关差异（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动力学最小模型），并比较关系 2. 检测 β 细胞中与祖先相关的差异。 胰岛素分泌能力（按GPA），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危险因素以及血管终末器官损伤（主动脉脉搏波速度）。 三组之间的差异，并测试 FFA 通量与血统之间关系的差异 探索性目标：比较脂肪细胞衍生的与胰岛素相关的外泌体 microRNA。 各组之间的信号传导，并测量它们与 β 细胞胰岛素分泌能力的关联，以进行假设 因此，本提案将研究异位脂肪、FFA 通量和 β 细胞分泌之间是否存在关联。 因血统不同而影响心脏代谢风险，预计这最终可能导致血统特异性 治疗方案。

项目成果

Update on management of diabetic foot ulcers.

糖尿病足溃疡治疗的最新进展。

• 发表时间: 2018-01
• 影响因子: 5.2
• 作者: Everett, Estelle;Mathioudakis, Nestoras
• 通讯作者: Mathioudakis, Nestoras

Disparities in the Prevalence and Correlates of Disability in Older Immigrants in the USA: a Systematic Review of the Literature.

美国老年移民残疾患病率的差异及其相关性：文献的系统回顾。

• 发表时间: 2019-06
• 作者: Nkimbeng, Manka;Cudjoe, Joycelyn;Turkson;Commodore;Thorpe Jr, Roland J;Szanton, Sarah L
• 通讯作者: Szanton, Sarah L

Circulating estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the Women's Health Initiative Observational Study.

妇女健康倡议观察研究中当前激素使用者的循环雌激素与绝经后卵巢癌和子宫内膜癌的风险。

• 发表时间: 2019-11
• 作者: Trabert, Britton;Coburn, Sally B;Falk, Roni T;Manson, JoAnn E;Brinton, Louise A;Gass, Margery L;Kuller, Lewis H;Rohan, Thomas E;Pfeiffer, Ruth M;Qi, Lihong;Stefanick, Marcia L;Wentzensen, Nicolas;Anderson, Garnet L;Xu, Xia
• 通讯作者: Xu, Xia

Recruiting African Immigrant Women for Community-Based Cancer Prevention Studies: Lessons Learned from the AfroPap Study.

招募非洲移民妇女进行社区癌症预防研究：AfroPap 研究的经验教训。

• 发表时间: 2019-10
• 影响因子: 5.9
• 作者: Cudjoe, Joycelyn;Turkson;Ezeigwe, Angelica K;Commodore;Nkimbeng, Manka;Han, Hae
• 通讯作者: Han, Hae

Comparability of serum, plasma, and urinary estrogen and estrogen metabolite measurements by sex and menopausal status.

按性别和绝经状态划分的血清、血浆和尿液雌激素和雌激素代谢物测量值的可比性。

• 发表时间: 2019-01
• 作者: Coburn, Sally B;Stanczyk, Frank Z;Falk, Roni T;McGlynn, Katherine A;Brinton, Louise A;Sampson, Joshua;Bradwin, Gary;Xu, Xia;Trabert, Britton
• 通讯作者: Trabert, Britton