Metabolomics of low-trauma fracture among older women with diabetes

描述(申请人提供)：在相关的医疗并发症中，糖尿病与低创伤骨折有关：与没有糖尿病的老年妇女相比，患有糖尿病的老年妇女的骨折风险是前者的2倍。矛盾的是，尽管糖尿病女性的平均骨矿密度较高，但风险仍会增加。长期目标是了解老年人中的糖尿病如何导致骨质疏松症和低创伤骨折。这项应用的目的是在老年糖尿病女性中确定与骨折相关的候选代谢特征。中心假设是，与没有骨折病史的老年糖尿病女性相比，那些低创伤骨折女性的代谢特征将显著不同。先前的研究已经表明，与脂肪酸和氨基酸代谢相关的代谢特征与糖尿病相关，存在显著差异。此外，在以动物为基础的骨质疏松症模型中，利用靶向代谢组学，观察到脂肪酸和支链氨基酸水平存在显著差异。这项拟议研究的基本原理是，一旦知道老年女性糖尿病患者的候选代谢特征，就可以在前瞻性研究中确定其对老年女性糖尿病患者骨折风险的影响。在这项拟议的横断面研究中，年龄为�65岁的糖尿病女性从普通内分泌和初级保健诊所招募，将致力于以下目标：1)评估有和没有低创伤骨折病史的老年糖尿病女性的氨基酸、有机酸和酰肉碱水平；2)比较无低创伤骨折病史的老年糖尿病女性与有骨折病史的老年糖尿病女性的代谢特征。在第一个下 目的：在控制了骨代谢和功能状态两项指标后，将使用靶向代谢组学方法来衡量低创伤骨折病史与支链氨基酸和酰肉碱水平之间的关系。在第二个目标下，将使用非靶向代谢组学来衡量低创伤骨折病史与其他代谢物类别之间的关联。通过利用代谢组学，该方法在识别与骨折相关的候选代谢谱方面是创新的。鉴于糖尿病在老年人中的患病率越来越高，以及与骨折相关的大量发病率，这项建议具有重要意义，因为了解这一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参考，以开发临床适用的前瞻性筛查工具 识别高危个体。

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.