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

描述患有 1 型糖尿病的老年人骨骼脆弱的机制

• 批准号: 10604862
• 负责人: MARY L BOUXSEIN
• 金额: $ 46.62万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-22 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10604862
• 关键词: Adult; Affect; Blood Vessels; Blood flow; Bone Density; Bone Diseases; Bone structure; Clinical; Cohort Studies; Complication; Complications of Diabetes Mellitus; Cross-Sectional Studies; Dependence; Diabetes Mellitus; Diabetic Angiopathies; Disease; Distal; Elderly; Foundations; Fracture; Functional disorder; Funding; Future; Health; Hip Fractures; Human; Impairment; Insulin-Dependent Diabetes Mellitus; Kidney Diseases; Leg; Link; Lower Extremity; Mediating; Microvascular Dysfunction; Near-Infrared Spectroscopy; Neuropathy; Nitric Oxide; Nitroglycerin; Outcome; Patients; Peripheral; Population; Regulation; Research; Retina; Retinal Diseases; Skeletal Muscle; Skin; Smooth Muscle; Thick; Time; Tissues; United States National Institutes of Health; Vascular Diseases; Vascular calcification; Vasodilation; Visit; Work; active control; arterial stiffness; bone; bone circulation; bone fragility; bone health; bone strength; burden of illness; cohort; cortical bone; cost efficient; diabetic; fracture risk; glycemic control; high risk; improved; in vivo; insight; insulin dependent diabetes mellitus onset; longitudinal analysis; meetings; non-diabetic; novel; novel strategies; parent grant; reactive hyperemia; response; skeletal; substantia spongiosa; tibia; vascular bed; vasoconstriction

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.

项目概要 当前提案是对最近资助的 R01DK124710 的竞争性修订，将扩大范围 以及家长补助金的潜在影响。骨骼脆弱是 1 型糖尿病 (T1D) 公认的并发症 并受到老年人的特别关注。然而，骨骼脆弱的机制尚不清楚。 明白了。虽然血管缺陷是众所周知的糖尿病并发症，但它们对骨血流量的影响 监管尚未探索。因此，该提案旨在调查糖尿病引起的疾病的贡献 父母授予的老年人群中血管缺陷对骨循环和骨骼脆弱性的影响。 使用一种新方法，近红外光谱 (NIRS)，我们将无创地评估胫骨血流量 人类并且每时每刻。采用 NIRS，目标 1 将调查老年人是否患有 与 T1D 相比，T1D 的胫骨脉管系统肌源性血管舒张较小，肌源性血管收缩较大 到非糖尿病控制。目标 2 将探讨患有 T1D 的老年人是否减弱了一氧化氮 (NO) 介导的功能 与非糖尿病对照相比，胫骨脉管系统的血管舒张。此外，Aim 3 将探索 胫骨血管反应的关系（肌源性血管舒张、肌源性血管收缩、NO介导的 血管舒张）对微血管疾病负担、周围血管钙化和老年人血糖控制的影响 患有 T1D 的成人。最后，目标 4 将研究胫骨血管反应与胫骨之间的关系 患有 T1D 的老年人的微结构。我们组建了一支高度跨学科的团队 互补的专业知识来进行这项研究，我们将利用家长资助的现有研究队列 以极具成本效益的方式；当前提案中将利用对母公司补助金的多项评估 而且患者的负担很小，只需要一次研究访问。拟议的研究将提供第一个 成人 T1D 体内骨血流调节的特征分析将增加宝贵的见解 研究血管并发症如何损害患有 T1D 的老年人的骨骼结构和强度。 该项目的成功完成将为未来研究新疗法奠定基础 患有糖尿病的老年人的骨骼健康。