Metabolomic & Radiographic Markers of Fracture Risk Among Older Adults with Diabetes

代谢组学

• 批准号: 10333346
• 负责人: Richard Hsang-Yang Lee
• 金额: $ 8.93万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10333346
• 关键词: 3-Dimensional; Abdomen; Address; Adult; Affect; Age; American; Area; Biological Markers; Biomechanics; Body mass index; Bone Density; Branched-Chain Amino Acids; Cardiovascular Diseases; Case-Control Studies; Chronic; Clinical; Clinical Assessment Tool; Clinical Data; Clinical assessments; Communities; Complications of Diabetes Mellitus; Contralateral; County; Data; Development; Diabetes Mellitus; Diagnostic; Disease; Dual-Energy X-Ray Absorptiometry; Elderly; Endocrinologist; Epidemiology; Etiology; Femur; Fostering; Fracture; Gender; Glycosylated hemoglobin A; Goals; Health; Hip Fractures; Hip region structure; Individual; Intervention; Laboratories; Length; Measures; Mediating; Medical; Metabolic; Metabolic Bone Diseases; Metabolic Marker; Metabolic dysfunction; Methods; Minerals; Modulus; Morbidity - disease rate; Neck; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; North Carolina; Participant; Pelvis; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Population; Positioning Attribute; Prevention; Prevention strategy; Public Health; Publishing; Questionnaires; Renal function; Reporting; Research; Research Activity; Research Personnel; Resources; Risk; Sampling; Scanning; Serum; Societies; Source; Statistical Data Interpretation; Techniques; Technology; Testing; Tissues; Training; Translational Research; Trauma; United States National Institutes of Health; Urine; Woman; Work; acylcarnitine; adjudicate; base; biomechanical engineering; biomechanical test; bone; bone health; bone quality; bone strength; career development; clinical biomarkers; clinical development; clinical epidemiology; clinical risk; cohort; comorbidity; computerized; diabetic; epidemiology study; fall risk; falls; fracture risk; high resolution imaging; improved; innovation; materials science; medical complication; meetings; men; metabolomics; mortality; novel marker; osteoporosis with pathological fracture; personalized medicine; prevent; radiological imaging; reconstruction; research clinical testing; risk stratification; screening; skills; stem; symposium; tool

ABSTRACT Among its medical complications, type 2 diabetes mellitus in older adults is associated with a two-fold increase in the risk of hip and other low-trauma bone fractures. Paradoxically, this increased risk occurs despite a higher average bone mineral density. This increased fracture risk is likely multifactorial, stemming from metabolic dysfunction that results in both increased falls risk and decreased bone strength. However, fracture risk stratification currently is limited largely to bone density testing and clinical risk tools that do not perform adequately for adults with diabetes. Because bone is both a metabolic and structural tissue, metabolomics and biomechanical analyses would be particularly useful for developing and assessing new measures of fracture risk. The objective of this application is to develop and evaluate radiographic and laboratory biomarkers of fracture risk among older adults with diabetes, utilizing biomechanical and translational measures. The proposed research has the following aims: 1) Determine the association between metabolomic profiles and incident clinical fracture among older adults with diabetes; 2) Compare geometric and biomechanical measures at the femoral neck and intertrochanteric region among older adults with diabetes, with and without hip fracture. This application builds upon the prior published work and clinical expertise of the Principle Investigator, Dr. Richard Lee, and provides him additional research skills to assist with his career development goal of understanding the interaction of chronic medical conditions on the bone health of older adults, focusing on diabetes. Dr. Lee is a dual-trained Geriatrician and Endocrinologist with expertise in metabolic bone disease. The primary training goals of this proposal include the following: 1) Develop laboratory and analytical skills in translational science that will be used in the development and evaluation of clinical biomarkers, including –omics technologies; 2) Acquire principles and skills in biomechanical engineering and materials science to integrate with clinical and epidemiological analyses. By integrating biomechanical engineering and metabolomics approaches with epidemiologic research to identify new markers of fracture risk, this application addresses a significant source of morbidity and mortality among an increasing proportion of older adults.

摘要 在其医学并发症中，老年人的2型糖尿病与以下因素相关： 髋关节和其他低创伤骨折的风险增加两倍。巧合的是， 尽管平均骨矿物质密度较高，但仍会发生增加的风险。这种增加的骨折 风险可能是多因素的，源于代谢功能障碍，导致两者增加 福尔斯风险和骨强度降低。然而，骨折风险分层目前是有限的 主要是骨密度测试和临床风险工具，这些工具对成年人来说并不充分 患有糖尿病由于骨既是代谢组织又是结构组织，因此代谢组学和 生物力学分析对于开发和评估新的 骨折风险评估。本申请的目的是开发和评估 老年糖尿病患者骨折风险的放射学和实验室生物标志物， 利用生物力学和平移测量。拟议的研究有以下几点 目的：1）确定代谢组学特征与临床骨折事件之间的关系 2）比较糖尿病患者的几何和生物力学测量结果， 老年糖尿病患者的股骨颈和转子间区域，有和无髋关节 骨折该应用程序建立在先前发表的工作和临床专业知识的基础上， 首席研究员理查德·李博士，并为他提供额外的研究技能，以协助 他的职业发展目标是了解慢性疾病与健康之间的相互作用， 老年人的骨骼健康，重点是糖尿病。李博士是一位受过双重训练的老年病学家， 具有代谢性骨病专业知识的内分泌学家。培训的主要目标是 建议包括以下内容：1）发展转化科学的实验室和分析技能 将用于临床生物标志物的开发和评估，包括-组学 2）掌握生物力学工程和材料的原理和技能 科学与临床和流行病学分析相结合。通过整合生物力学 工程和代谢组学方法与流行病学研究，以确定新的标志物 骨折的风险，这一应用程序解决了发病率和死亡率的一个重要来源， 越来越多的老年人。

项目成果

Diabetes is associated with a lower minimum moment of inertia among older women: An analysis of 3D reconstructions of clinical CT scans.

• DOI: 10.1016/j.jbiomech.2021.110707
• 发表时间: 2021-11-09
• 期刊: JOURNAL OF BIOMECHANICS
• 影响因子: 2.4
• 作者: Heckelman, Lauren N.;Wesorick, Benjamin R.;DeFrate, Louis E.;Lee, Richard H.
• 通讯作者: Lee, Richard H.

The break in FRAX: Equity concerns in estimating fracture risk in racial and ethnic minorities.

• DOI: 10.1111/jgs.17316
• 发表时间: 2021-09
• 期刊: JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
• 影响因子: 6.3
• 作者: Reid, Hadley W.;Selvan, Bharathi;Batch, Bryan C.;Lee, Richard H.
• 通讯作者: Lee, Richard H.