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: 10469729
• 负责人: Melanie Schorr Haines
• 金额: $ 7.27万
• 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/10469729
• 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.

项目总结/摘要 肥胖是一个众所周知的心脏代谢疾病的危险因素和日益严重的公共卫生问题。不过小 已知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）， 特别是在超重/肥胖的年轻人中。拟议的研究有可能确定目标 来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的低肌肉质量）和受损的肌肉 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）导致DM风险升高 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导致相对肌肉减少症 肌肉质量受损，导致糖尿病风险增加。 候选人是哈佛医学院的医学讲师和 马萨诸塞州总医院（MGH）是一家高素质的医院，致力于开发 作为一名独立调查员。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资助研究所需的数据。她的长- 长期目标是成为一个独立的面向患者的研究人员，利用遗传流行病学，内分泌 生理学和复杂的成像技术，以阐明可能有助于增加的机制， 超重/肥胖的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。她有着出色的成功记录，包括奖项，试点赠款和 出版物，并由一个专家和高度投资的导师团队组成的成功， 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者 流行病学。她和她的导师们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和哈佛医学院的制度环境非常出色，拥有多种资源 可从MGH医学系、MGH临床研究部和哈佛大学获得 临床和转化科学中心，所有这些都提供了无数的教学机会，设施和 支持候选人。神经内分泌科和内科已经做了一个强有力的 对候选人的承诺，包括90%的保护时间，空间，研究协调员的支持和教师 任命，目的是促进候选人作为独立调查员的职业生涯。

项目成果

Endocrine complications of anorexia nervosa.

• DOI: 10.1186/s40337-023-00744-9
• 发表时间: 2023-02-15
• 期刊: JOURNAL OF EATING DISORDERS
• 影响因子: 4.1
• 作者: Haines, Melanie S.

Case 1-2023: A 49-Year-Old Man with Hypokalemia and Paranoia.

病例 1-2023：一名 49 岁男性，患有低钾血症和偏执狂。

• DOI: 10.1056/nejmcpc2211366
• 发表时间: 2023
• 期刊: The New England journal of medicine
• 作者: Vokoun,ChadW;Murphy,MarkC;Reynolds,KerryL;Haines,MelanieS
• 通讯作者: Haines,MelanieS

GnRH agonist-associated pituitary apoplexy: a case series and review of the literature.

GnRH 激动剂相关垂体卒中：病例系列和文献综述。

• DOI: 10.1007/s11102-021-01143-6
• 发表时间: 2021
• 期刊: Pituitary
• 影响因子: 3.8
• 作者: Guarda,FranciscoJ;Yu,Xiaoling;Shiraliyeva,Naila;Haines,MelanieS;Bradbury,Michael;Saylor,PhilipJ;Nachtigall,LisaB
• 通讯作者: Nachtigall,LisaB