Metabolomics of low-trauma fracture among older women with diabetes

老年糖尿病女性低创伤性骨折的代谢组学

• 批准号: 8757759
• 负责人: Richard Hsang-Yang Lee
• 金额: $ 7.85万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8757759
• 关键词: Address; Age; American; Amino Acids; Animals; Biological Markers; Bone Density; Branched-Chain Amino Acids; Clinic; Clinical Markers; Clinical Research; Cohort Studies; Collagen; Cross-Sectional Studies; Diabetes Mellitus; Diagnosis; Disease; Elderly; Endocrine; Fatty Acids; Fostering; Fracture; Frequencies; Future; Goals; Health; Human; Individual; Knowledge; Laboratories; Measurement; Measures; Metabolic; Metabolic Marker; Metabolism; Mission; Modeling; Morbidity - disease rate; Osteoporosis; Participant; Patients; Performance; Persons; Population; Prevalence; Primary Health Care; Prospective Studies; Public Health; Recording of previous events; Recruitment Activity; Research; Resources; Risk; SF-36; Sample Size; Sampling; Serum; Time; Trauma; Urine; Visit; Woman; acylcarnitine; aging population; base; bone; bone metabolism; bone quality; crosslink; design; diabetic; experience; falls; functional status; improved; innovation; medical complication; metabolomics; older women; organic acid; preclinical study; prevent; prospective; public health priorities; screening; self-reported functional status; stem; tool

DESCRIPTION (provided by applicant): Among its associated medical complications, diabetes is associated with low-trauma bone fracture: Compared to older women without diabetes, older women with diabetes have 2-times the fracture risk. Paradoxically, this increased risk occurs despite diabetic women having a higher average bone mineral density. The long-term goal is to understand how diabetes among older adults contributes to osteoporosis and low-trauma bone fractures. The objective of this application is to identify, among older, diabetic women, candidate fracture-related metabolic profiles. The central hypothesis is that compared to older, diabetic women without a fracture history, the metabolic profiles of those women with a low-trauma fracture will be significantly different. As prior studie have shown, there are significant differences in metabolic profiles, related to fatty acid and amino acid metabolism, associated with diabetes. Additionally, in an animal-based model of osteoporosis, significant differences were observed in the levels of fatty acids and branched chain amino acids, using targeted metabolomics. The rationale for the proposed study is that the contribution to incident fracture risk among older women with diabetes can be determined in prospective studies, once candidate metabolic profiles are known in this population. In this proposed, cross-sectional study of diabetic women, age ≥65 years, recruited from general endocrine and primary care clinics, the following aims will be addressed: 1) Assess the levels of amino acids, organic acids, and acylcarnitines in older women with diabetes, both with and without a history of low-trauma fracture; 2) Compare the metabolic profiles of older, diabetic women without a history of low-trauma fracture to those with a history of fracture. Under the first aim, after controlling for both measures of bone metabolism and functional status, the association between a history of low-trauma fracture and the levels of branched-chain amino acids and acylcarnitines, will be measured using targeted metabolomics. Under the second aim, the association between a history of low-trauma fracture and other metabolite classes will be measured using non-targeted metabolomics. The approach is innovative in identifying candidate, fracture-associated metabolic profiles, by utilizing metabolomics. Given the increasing prevalence of diabetes and substantial fracture-related morbidity among older adults, the proposal is significant because it is critically important to understand the key factors in thi population that contribute to low-trauma fractures. The results from the proposed study will inform the design of future studies to develop clinically applicable prospective screening tools to identify at-risk individuals.

描述（由申请人提供）：在其相关的医疗并发症中，糖尿病与低创伤骨折相关：与无糖尿病的老年女性相比，患有糖尿病的老年女性的骨折风险为2倍。奇怪的是，尽管糖尿病女性的平均骨矿物质密度较高，但这种风险仍会增加。长期目标是了解老年人糖尿病如何导致骨质疏松症和低创伤骨折。本申请的目的是在老年糖尿病女性中确定候选的糖尿病相关代谢谱。中心假设是，与没有骨折史的老年糖尿病女性相比，低创伤骨折女性的代谢特征将显着不同。如先前的研究所示，与糖尿病相关的脂肪酸和氨基酸代谢的代谢谱存在显著差异。此外，在基于动物的骨质疏松症模型中，使用靶向代谢组学观察到脂肪酸和支链氨基酸水平存在显著差异。这项研究的基本原理是，一旦在这一人群中已知候选代谢特征，就可以在前瞻性研究中确定老年糖尿病女性发生骨折风险的贡献。在这项拟定的横断面研究中，招募了来自普通内分泌和初级保健诊所的年龄≥65岁的糖尿病女性，目的如下：1）评估有和无低创伤骨折史的老年糖尿病女性的氨基酸、有机酸和酰基肉毒碱水平; 2）比较无低创伤骨折史的老年糖尿病女性与有骨折史的女性的代谢特征。在第一个目标下，在控制骨代谢和功能状态的测量后，将使用靶向代谢组学测量低创伤骨折史与支链氨基酸和酰基肉毒碱水平之间的关联。在第二个目标下，将使用非靶向代谢组学测量低创伤骨折史与其他代谢物类别之间的关联。该方法是创新的，在确定候选人，乳腺癌相关的代谢概况，通过利用代谢组学。考虑到老年人糖尿病患病率的增加和大量与骨折相关的发病率，该建议具有重要意义，因为了解该人群中导致低创伤骨折的关键因素至关重要。拟议研究的结果将为未来研究的设计提供信息，以开发临床适用的前瞻性筛选工具，以识别风险个体。