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: 8919214
• 负责人: Richard Hsang-Yang Lee
• 金额: $ 7.7万
• 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 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8919214
• 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; 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; amino acid metabolism; 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（由适用提供）：在其相关的医疗并发症中，糖尿病与低创伤性骨折有关：与没有糖尿病的老年妇女相比，糖尿病的老年妇女具有2次骨折风险。矛盾的是，这种增加的风险发生是dospite糖尿病妇女的平均骨矿物质密度较高。长期目标是了解老年人中糖尿病如何促进骨质疏松症和低创伤骨碎片。该应用的目的是确定糖尿病妇女，候选骨折相关的代谢谱。中心假设是，与没有骨折病史的老年糖尿病女性相比，那些骨折低的妇女的代谢特征将显着差异。如先前的工作室所表明的那样，与脂肪酸和氨基酸代谢有关的代谢谱存在显着差异，与糖尿病有关。此外，在基于动物的骨质疏松症模型中，使用靶向的代谢组学观察到脂肪酸和分支链氨基酸的水平显着差异。拟议的研究的理由是，一旦在该人群中知道候选代谢谱，就可以在前瞻性研究中确定老年糖尿病妇女的事件骨折风险的贡献。在这项提出的糖尿病妇女的横断面研究中，年龄为65岁，是从一般内分泌和初级保健诊所招募的，将解决以下目的：1）评估患有糖尿病的老年妇女的氨基酸，有机酸和酰基果碱的水平，无论是糖尿病患有低含量的糖尿病病史还是没有病史。 2）将没有低创伤性骨折病史的老年糖尿病妇女与有骨折史的糖尿病患者的代谢特征进行比较。在第一个 目的是在控制骨代谢和功能状态的测量结果之后，将使用靶向代谢组学测量低创伤裂缝史与分支链氨基酸和酰基肉碱的水平之间的关联。在第二个目标下，将使用非靶向代谢组学测量低创伤骨骨折与其他代谢物类别之间的关联。这种方法是通过利用代谢组学来识别候选，骨折相关的代谢谱的创新性。鉴于糖尿病患病率的增加和老年人与骨折相关的大量发病率的越来越大，因此该提案意义重大，因为了解促成低创伤性骨折的Thi人群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查工具 确定高危个人。