Relative Sarcopenia and Cardiometabolic Risk in Young Adults with Obesity

肥胖年轻人的相对肌肉减少症和心脏代谢风险

• 批准号: 10240291
• 负责人: Melanie Schorr Haines
• 金额: $ 19.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240291
• 关键词: Adult; Age Factors; Appointment; Atherosclerosis Risk in Communities; Award; Body mass index; Cardiometabolic Disease; Center for Translational Science Activities; Central obesity; Clinical; Clinical Investigator; Clinical Research; Clinical Sciences; Coronary Artery Risk Development in Young Adults Study; Data; Deposition; Elderly; Endocrine Physiology; Environment; Epidemiology; Faculty; Fatty acid glycerol esters; Fostering; Funding; Future; General Hospitals; Genetic Risk; Glucose; Goals; Grant; Hormones; Hospital Departments; Imaging Techniques; Impairment; Insulin Resistance; Lead; Link; Lipids; Massachusetts; Mediating; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Muscle; National Health and Nutrition Examination Survey; Neuroendocrinology; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Overweight; Peripheral; Phenotype; Prevalence; Prevention; Prospective Studies; Public Health; Publications; Radiology Specialty; Research; Research Personnel; Research Support; Resources; Risk; Risk Factors; Single Nucleotide Polymorphism; Skeletal Muscle; Somatotropin; Study Subject; Targeted Research; Testosterone; Thinness; Time; Training; United States National Institutes of Health; Visit; Woman; adiponectin; adult obesity; cardiometabolic risk; career; design; diabetes risk; follow-up; genetic epidemiology; genetic variant; hormone deficiency; instructor; lifestyle factors; medical schools; men; mitochondrial dysfunction; multidisciplinary; muscle form; musculoskeletal imaging; patient oriented; programs; recruit; reduced muscle mass; risk prediction model; sarcopenia; sex; skills; success; young adult

PROJECT SUMMARY/ABSTRACT Obesity is a well-known cardiometabolic disease risk factor and growing public health problem. However, little is known about the impact of muscle mass and quality on cardiometabolic risk, including type 2 diabetes (DM), especially in young adults with overweight/obesity. The proposed research has the potential to identify targets for the prevention and treatment of this public health problem. The central hypothesis is that relative sarcopenia (i.e. low muscle mass relative to BMI) and impaired muscle quality (i.e. intramyocellular lipid (IMCL) and mitochondrial dysfunction) contribute to higher DM risk over time in young adults with overweight/obesity. We also hypothesize that common genetic variants associated with insulin resistance, as well as obesity-related relative hormone deficiencies, contribute to relative sarcopenia and impaired muscle quality and lead to higher DM risk. The candidate is an Instructor of Medicine at Harvard Medical School and Assistant in Medicine at Massachusetts General Hospital (MGH) who is highly qualified for and deeply committed to developing a career as an independent investigator. Her short-term goal is to develop the skills and obtain the preliminary data necessary to make the transition to her first R-level independent NIH grant-supported research. Her long- term goal is to become an independent patient-oriented researcher leveraging genetic epidemiology, endocrine physiology and sophisticated imaging techniques to elucidate mechanisms that may contribute to increased cardiometabolic risk in young adults with overweight/obesity, and to identify potential targets for both prevention and treatment. She has an outstanding track record of success, including awards, pilot grants and publications, and is supported by an expert and highly invested mentorship team composed of successful, NIH-supported clinical investigators in Neuroendocrinology, Radiology, Epidemiology and Genetic Epidemiology. She and her mentors have designed a targeted training plan consisting of co-mentorship and a didactic program. The institutional environment is outstanding at MGH and Harvard Medical School, with multiple resources available from the MGH Department of Medicine, the MGH Division of Clinical Research, and the Harvard Clinical and Translational Science Center, all of which offer a myriad of didactic opportunities, facilities and support to the candidate. The Neuroendocrine Unit and Department of Medicine have made a strong commitment to the candidate, including 90% protected time, space, study coordinator support and a faculty appointment, with the goal of fostering the candidate's career as an independent investigator.

项目概要/摘要 肥胖是众所周知的心脏代谢疾病危险因素和日益严重的公共卫生问题。然而，很少 了解肌肉质量和质量对心脏代谢风险的影响，包括 2 型糖尿病 (DM)， 尤其是超重/肥胖的年轻人。拟议的研究有可能确定目标 以预防和治疗这一公共卫生问题。 中心假设是相对肌肉减少症（即相对于 BMI 的肌肉质量较低）和肌肉受损 随着时间的推移，质量（即肌细胞内脂质 (IMCL) 和线粒体功能障碍）会导致更高的 DM 风险 超重/肥胖的年轻人。我们还假设常见的遗传变异与 胰岛素抵抗以及与肥胖相关的相对激素缺乏会导致相对肌肉减少症 和肌肉质量受损并导致更高的 DM 风险。 该候选人是哈佛医学院的医学讲师和医学助理 马萨诸塞州总医院 (MGH) 拥有高素质并坚定致力于发展 独立调查员的职业生涯。她的短期目标是发展技能并获得初步的 过渡到她的第一个 R 级独立 NIH 拨款支持的研究所需的数据。她的长—— 学期目标是成为一名独立的、以患者为导向的研究人员，利用遗传流行病学、内分泌学 生理学和复杂的成像技术来阐明可能有助于增加的机制 超重/肥胖年轻人的心脏代谢风险，并确定两者的潜在目标 预防和治疗。她拥有杰出的成功记录，包括奖项、试点补助金和 出版物，并得到专家和高度投入的指导团队的支持，该团队由成功的、 NIH 支持的神经内分泌学、放射学、流行病学和遗传学临床研究人员 流行病学。她和她的导师设计了一个有针对性的培训计划，包括共同指导和 教学计划。 MGH和哈佛医学院机构环境优秀，资源多元 可从 MGH 医学系、MGH 临床研究部和哈佛大学获取 临床和转化科学中心，所有这些中心都提供无数的教学机会、设施和 对候选人的支持。神经内分泌科和医学科已做出了强有力的贡献 对候选人的承诺，包括 90% 受保护的时间、空间、学习协调员支持和教师 任命，目的是促进候选人作为独立调查员的职业生涯。