Biomechanical mechanisms underlying skeletal fragility in older adults with Type 1 diabetes

患有 1 型糖尿病的老年人骨骼脆弱的生物力学机制

• 批准号: 10012242
• 负责人: MARY L BOUXSEIN
• 金额: $ 31.3万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10012242
• 关键词: 3-Dimensional; Address; Adult; Advanced Glycosylation End Products; Age; Aging; Architecture; Area; Autopsy; Biomechanics; Bone Density; Bone Matrix; Bone structure; Clinical; Complication; Complications of Diabetes Mellitus; Cross-Sectional Studies; Data; Development; Diabetes Mellitus; Diagnosis; Disease; Dual-Energy X-Ray Absorptiometry; Elderly; Femur; Finite Element Analysis; Fourier Transform; Fracture; Glucose; Goals; Health; Hip Fractures; Hip region structure; Image; Incidence; Individual; Inferior; Insulin-Dependent Diabetes Mellitus; Knowledge; Lead; Life Expectancy; Longevity; Methods; Microvascular Dysfunction; Nature; Neck; Operative Surgical Procedures; Osteoporosis; Outcome; Patients; Periodicity; Postmenopause; Property; Risk; Serum; Skin; Specimen; Structure; Tissues; Vulnerable Populations; Woman; X-Ray Computed Tomography; base; bone; bone fragility; bone mass; bone quality; bone strength; clinical care; cohort; cortical bone; diabetic; experience; fracture risk; glucose monitor; glycemic control; high risk; improved; in vivo; insight; men; non-diabetic; novel; pentosidine; prevent; repaired; skeletal; substantia spongiosa

PROJECT SUMMARY / ABSTRACT As advances in clinical care continue to improve the lifespan of adults with type 1 diabetes (T1D), these patients have experienced an increase in aging-related diseases, including osteoporosis. As compared to nondiabetic adults, patients with T1D have an increased risk of fractures, particularly at the hip. This clinically important problem is further compounded by the fact that patients with T1D experience poorer outcomes following a fracture. However, little is currently known about the effect of T1D on bone composition and bone quality, particularly in older adults. In this proposal, our goal is to investigate biomechanical mechanisms of skeletal fragility in postmenopausal women and men age > or = to 50 years with T1D. We will compare tissue level bone biomechanical properties and bone composition using ex vivo femoral specimens from adults with longstanding T1D (50+ year duration) and matched nondiabetic controls, as well as from adults with and without T1D who are undergoing surgical repair of hip fracture. Using state-of-the-art methods, successful completion of our proposed aims will provide novel insights about the alterations in bone structure and quality that contribute to skeletal fragility in older adults with T1D, in whom fracture risk is highest. In addition, our findings will clarify the impact of diabetic history and accumulation of advanced glycation end-products on skeletal fragility in T1D. Addressing these critical gaps in knowledge will ultimately allow clinicians to develop rational approaches to prevent fractures in patients with T1D.

项目摘要 /摘要 随着临床护理的进步继续改善1型糖尿病（T1D）成年人的寿命，这些患者的衰老疾病（包括骨质疏松症）的寿命增加了。 与非糖尿病成年人相比，T1D患者的裂缝风险增加，尤其是在臀部。 T1D患者在骨折后的结局较差，这一事实进一步加剧了这个临床上重要的问题。 但是，目前，关于T1D对骨成分和骨质质量的影响，尤其是在老年人中，知之甚少。 在此提案中，我们的目标是研究绝经后男女骨骼脆弱性的生物力学机制>或= 50岁以上T1D。 我们将使用具有长期T1D（50岁以上持续时间）和非糖尿病对照的成年人以及有和没有T1D的成年人的股骨股生物力学特性和骨组成比较组织水平的骨骼生物力学特性和骨骼组成。 使用最先进的方法，我们提出的目标的成功完成将提供有关骨骼结构和质量改变的新见解，这些变化导致T1D老年人的骨骼脆弱性，其中断裂风险最高。此外，我们的发现将阐明糖尿病病史和晚期糖基化最终产物对T1D骨骼脆弱性的积累的影响。 解决知识中的这些关键差距最终将使临床医生能够开发出理性方法以防止T1D患者的骨折。