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.

项目总结/摘要 骨骼脆弱性是最近认识到的1型糖尿病（T1 D）并发症，特别值得关注 在老年人中。T1 D患者发生髋部骨折的风险是对照组的5- 7倍。 非糖尿病患者然而，T1 D骨折风险增加的机制并不清楚， 明白该建议旨在描述老年人髋关节骨骼脆弱的机制， T1 D，其中骨折风险最高。目的1将评价骨密度、结构 绝经后女性和年龄> 50岁男性T1 D患者的骨强度和皮质骨质量比较 非糖尿病对照组。目的2将调查糖尿病并发症的潜在贡献，如 血糖分析（使用连续血糖监测）、晚期糖基化终产物（AGEs）和 微血管疾病，骨骼终点和年龄相关的骨丢失。最后，Aim 3将利用体外 股骨标本，以直接评估成人股骨骨成分和生物力学强度， 长期的T1 D我们已经组建了一个多学科专家团队来进行这项研究，我们将 利用现有的丰富轮廓的队列，并招募新的队列进行详细的骨骼表型分析， 阐明T1 D对骨骼健康的影响。我们的研究将提供新的见解，改变股骨 T1 D的骨结构和质量，并将阐明血糖控制和糖尿病并发症对 骨骼脆弱该项目的成功完成将为降低老年人骨折风险的战略提供信息。 成人T1 D