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: 10017186
• 负责人: MARY L BOUXSEIN
• 金额: $ 30.31万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017186
• 关键词: 3-Dimensional; Address; Adult; Advanced Glycosylation End Products; Age; Aging; Area; Autopsy; Biomechanics; Bone Density; Bone Matrix; Bone structure; Clinical; 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; Recording of previous events; Risk; Serum; Skin; Specimen; Structure; Tissues; Vulnerable Populations; Woman; X-Ray Computed Tomography; base; bone; bone fragility; 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.

项目概要/摘要 随着临床护理的进步不断延长 1 型糖尿病 (T1D) 成人患者的寿命，这些患者的衰老相关疾病（包括骨质疏松症）有所增加。 与非糖尿病成年人相比，1 型糖尿病患者骨折的风险更高，尤其是髋部骨折。 1型糖尿病患者骨折后的预后较差，这一事实进一步加剧了这一临床上重要的问题。 然而，目前人们对 T1D 对骨成分和骨质量的影响知之甚少，尤其是对老年人。 在本提案中，我们的目标是研究绝经后女性和 50 岁以上 T1D 男性骨骼脆弱的生物力学机制。 我们将使用长期 T1D（病程 50 年以上）成人和匹配的非糖尿病对照，以及接受髋部骨折手术修复的患有和不患有 T1D 成人的离体股骨标本，比较组织水平的骨生物力学特性和骨成分。 使用最先进的方法，成功完成我们提出的目标将为骨结构和质量的改变提供新的见解，这些改变会导致患有 T1D 的老年人骨骼脆弱，而老年 T1D 患者的骨折风险最高。此外，我们的研究结果将阐明糖尿病史和晚期糖基化终产物的积累对 1 型糖尿病骨骼脆性的影响。 解决这些关键的知识差距最终将使临床医生能够开发出合理的方法来预防 1 型糖尿病患者骨折。