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

项目摘要/摘要 随着临床护理的进步继续延长成年1型糖尿病(T1D)患者的寿命，这些患者经历了与衰老相关的疾病的增加，包括骨质疏松症。与非糖尿病成人相比，患有T1D的患者发生骨折的风险增加，尤其是髋部。T1D患者在骨折后的预后较差，这一事实进一步加剧了这一临床上重要的问题。然而，目前对T1D对骨成分和骨质量的影响知之甚少，特别是在老年人中。在这项建议中，我们的目标是研究绝经后女性和男性骨骼脆性的生物力学机制；年龄&gt；或=50岁T1D。我们将使用长期患有T1D的成年人(病程超过50年)和匹配的非糖尿病对照组的体外股骨标本，以及接受髋部骨折手术修复的患有和不患有T1D的成年人的股骨标本，比较组织水平、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变化提供新的见解，这些变化导致患有T1D的老年人骨骼脆性，在T1D患者中，骨折风险最高。此外，我们的发现将阐明糖尿病病史和晚期糖基化终末产物积累对T1D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合理的方法来预防T1D患者的骨折。

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.