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.

项目摘要 当前的提案是对最近资助的R01DK124710的竞争性修订版，它将扩大范围 父母赠款的潜在影响。骨骼脆弱性是1型糖尿病（T1D）公认的并发症 在老年人中特别关注。但是，骨骼脆弱性的机制很差 理解。尽管血管缺陷是糖尿病的众所周知的并发症，但它们对骨血流的影响 监管尚未探讨。因此，该提案旨在调查糖尿病引起的贡献 父母赠款老年人队列中骨循环和骨骼脆弱性的血管缺陷。 使用新型方法，近红外光谱法（NIR），我们将非侵入性评估胫骨血流 人类和一刻的基础。 AIM 1雇用NIR，将调查是否有 T1D在胫骨血管中具有较低的肌源性血管舒张和更大的肌源血管收缩。 进行非糖尿病控制。 AIM 2将探索T1D老年人是否有钝氧化一氧化氮（NO）介导的 与非糖尿病对照相比，胫骨血管中的血管舒张。此外，AIM 3将探索 胫骨血管反应的关系（肌原性血管舒张，肌源性血管收缩，无介导 血管舒张）至微血管疾病负担，周围血管钙化和血糖控制 T1D的成年人。最后，AIM 4将研究胫骨血管反应与胫骨之间的关系 T1D老年人的微观结构。我们已经组建了一个高度跨学科的团队 进行这项研究的补充专业知识，我们将利用父母赠款的现有研究队列 以高度成本效益的方式；当前提案将使用对父母赠款的几项评估 并且患者负担将很小，需要一次学习。拟议的研究将提供第一个 T1D成年人中体内骨血流量调节的表征，并将添加宝贵的见解 T1D老年人的血管并发症如何损害骨骼结构和强度。 该项目的成功完成将为未来的工作提供基础 老年人糖尿病的骨骼健康。