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: 10554392
• 负责人: Elaine Wei-Yin Yu
• 金额: $ 71.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10554392
• 关键词: 3-Dimensional; Acceleration; Address; Adult; Advanced Glycosylation End Products; Age; Age-Related Bone Loss; Area; Biomechanics; Bone Density; Bone Matrix; Bone structure; Complication; Complications of Diabetes Mellitus; Continuous Glucose Monitor; Data; Development; Diabetes Mellitus; Dual-Energy X-Ray Absorptiometry; Elderly; Ethnic Origin; Exhibits; Femur; Finite Element Analysis; Fourier Transform; Fracture; Glucose; Glycosylated hemoglobin A; Health; Hip Fractures; Hip region structure; Image; Incidence; Individual; Inferior; Insulin-Dependent Diabetes Mellitus; Intervention; Knowledge; Life Expectancy; Literature; Maps; Measures; Microvascular Dysfunction; Nature; Neck; Osteogenesis; Outcome; Oxidative Stress; Patients; Periodicity; Peripheral; Phenotype; Postmenopause; Prospective Studies; Race; Risk; Serum; Skeleton; Skin; Specimen; Structure; Techniques; Testing; Thinness; Woman; X-Ray Computed Tomography; age related; bone; bone fragility; bone health; bone quality; bone strength; cohort; cortical bone; follow-up; fracture risk; glycemic control; high risk; hip bone; improved; in vivo; insight; mechanical properties; men; multidisciplinary; non-diabetic; novel; pentosidine; prevent; prospective; recruit; sex; skeletal; substantia spongiosa

PROJECT SUMMARY / ABSTRACT Skeletal fragility is a recently recognized complication of Type 1 diabetes (T1D), and is of particular concern among older adults. Patients with T1D have a striking 5- to 7-fold higher risk of hip fractures as compared to nondiabetics. However, the mechanisms that underlie the increased fracture risk in T1D are poorly understood. This proposal seeks to delineate the mechanisms of skeletal fragility at the hip in older adults with T1D, among whom fracture risk is highest. Aim 1 will evaluate prospective changes in bone density, structure, strength, and cortical bone quality in postmenopausal women and men age 50 years with T1D as compared to nondiabetic controls. Aim 2 will investigate the potential contributions of diabetic complications, such as glycemic profiling (using continuous glucose monitoring), advanced glycation endproducts (AGEs) and microvascular disease, to skeletal endpoints and age-related bone loss. Finally, Aim 3 will utilize ex vivo femoral specimens to directly assess femoral bone composition and biomechanical strength among adults with longstanding T1D. We have assembled a multidisciplinary team of experts to perform this study, and we will leverage existing richly profiled cohorts as well as recruit new cohorts for detailed skeletal phenotyping to clarify the impact of T1D on bone health. Our studies will provide novel insights about alterations in femoral bone structure and quality in T1D, and will clarify the impact of glycemic control and diabetic complications on skeletal fragility. Successful completion of this project will inform strategies to lower fracture risk among older adults with T1D.

项目摘要 /摘要 骨骼脆弱性是最近公认的1型糖尿病并发症（T1D），特别关注 在老年人中。 T1D患者的髋部骨折风险高5至7倍，而 非糖尿病。但是，T1D的骨折风险增加的基础的机制很差 理解齿。该提议旨在描述老年人的髋部骨骼脆弱性机理 T1D，骨折风险最高。 AIM 1将评估骨密度，结构，结构的前瞻性变化 绝经后男性和男性的力量和皮质骨质量与T1D相比 进行非糖尿病控制。 AIM 2将研究糖尿病并发症的潜在贡献，例如 血糖分析（使用连续的葡萄糖监测），晚期糖基化最终产物（年龄）和 微血管疾病，骨骼终点和与年龄相关的骨质流失。最后，AIM 3将使用离体 股骨标本直接评估成年人的股骨组成和生物力学强度 长期T1D。我们已经组建了一个多学科的专家团队来进行这项研究，我们将 利用现有的丰富介绍的队列，并招募新的同类群体来详细的骨骼表型 阐明T1D对骨骼健康的影响。我们的研究将提供有关股骨改变的新见解 T1D的骨结构和质量，将阐明血糖控制和糖尿病并发症对 骨骼脆弱性。该项目的成功完成将为策略提供降低老年骨折风险的策略 T1D的成年人。