Delineating mechanisms of skeletal fragility in older adults with Type 1 Diabetes

项目总结 目前的提案是对最近资助的R01DK124710的竞争性修订，将扩大范围 以及父母拨款的潜在影响。骨骼脆性是公认的1型糖尿病(T1D)并发症 在老年人中尤其令人担忧。然而，骨骼脆性的潜在机制很差。 明白了。虽然血管缺陷是众所周知的糖尿病并发症，但它们对骨骼血液流动的影响 监管还没有得到探索。因此，这项建议试图调查糖尿病引起的 在父母补助金的老年人队列中，骨循环和骨骼脆性方面的血管缺陷。 使用一种新的方法，近红外光谱(NIRS)，我们将非侵入性地评估胫骨血流。 人类，在每一刻的基础上。利用NIR，Aim 1将调查老年人是否患有 与T1D相比，T1D胫骨血管的肌源性血管扩张较轻，肌源性血管收缩较大 至非糖尿病对照组。Aim 2将探索患有T1D的老年人是否钝化了一氧化氮(NO)介导的 与非糖尿病对照组相比，胫骨血管系统中的血管扩张。此外，目标3将探索 胫骨血管反应(肌源性血管扩张、肌源性血管收缩、一氧化氮介导)的关系 血管扩张)与微血管疾病负担、外周血管钙化和血糖控制有关 成人T1D。最后，目标4将调查胫骨血管反应和胫骨之间的关系 患有T1D的老年人中的微体系结构。我们已经组建了一个高度跨学科的团队， 进行这项研究的互补专业知识，我们将利用父母资助的现有研究队列 以极具成本效益的方式；将在目前的提案中使用对父母赠款的若干评估 而且患者的负担将是最小的，只需要一次研究访问。拟议中的研究将提供第一个 曾表征成人T1D患者体内骨血流调节，将增加宝贵的洞察力 血管并发症可能如何损害患有T1D的老年人的骨骼结构和强度。 该项目的成功完成将为今后的新型治疗工作奠定基础。 老年糖尿病患者的骨骼健康。

PROJECT SUMMARY The current proposal is a competitive revision for the recently funded R01DK124710 that will expand the scope and potential impact of the parent grant. Skeletal fragility is a recognized complication of Type 1 diabetes (T1D) and is of particular concern among older adults. However, the mechanisms underlying skeletal fragility are poorly understood. While vascular deficits are a well-known complication of diabetes, their effect on bone blood flow regulation has not been explored. Thus, this proposal seeks to investigate the contribution of diabetes-induced vascular deficits on bone circulation and skeletal fragility within the cohort of older adults of the parent grant. Using a novel approach, near infrared spectroscopy (NIRS), we will non-invasively assess tibial blood flow in humans and on a moment-by-moment basis. Employing NIRS, Aim 1 will investigate whether older adults with T1D have lesser myogenic vasodilation and greater myogenic vasoconstriction in the tibial vasculature compared to nondiabetic controls. Aim 2 will explore whether older adults with T1D have blunted nitric oxide (NO)-mediated vasodilation in the tibial vasculature compared to nondiabetic controls. Furthermore, Aim 3 will explore the relationship of tibial vascular responses (myogenic vasodilation, myogenic vasoconstriction, NO-mediated vasodilation) to microvascular disease burden, peripheral vascular calcification, and glycemic control in older adults with T1D. Lastly, Aim 4 will investigate the relationship between tibial vascular responses and tibial microarchitecture among older adults with T1D. We have assembled a highly interdisciplinary team with complementary expertise to perform this study and we will leverage the existing study cohort of the parent grant in a highly cost-efficient manner; several assessments of the parent grant will be utilized in the current proposal and the patient burden will be minimal, requiring a single study visit. The proposed research will provide the first ever characterization of in vivo bone blood flow regulation among adults with T1D and will add invaluable insight into how vascular complications may compromise bone structure and strength in older adults with T1D. Successful completion of this project will provide the foundation for future work towards novel treatments for bone health in older adults with diabetes.