Delineating mechanisms of skeletal fragility in older adults with Type 1 Diabetes

项目摘要/摘要 骨骼脆性是最近发现的1型糖尿病(T1D)的并发症，特别令人担忧 在老年人中。与患有T1D的患者相比，T1D患者发生髋部骨折的风险高出5到7倍 非糖尿病患者。然而，T1D骨折风险增加的机制尚不清楚。 明白了。这项建议试图描绘老年人髋部骨骼脆性的机制。 T1D，其中骨折风险最高。目标1将评估骨密度、结构、 绝经后50岁女性和男性与T1D的强度和皮质骨质量的比较 至非糖尿病对照组。目标2将调查糖尿病并发症的潜在贡献，例如 血糖分析(使用连续血糖监测)、高级糖基化终末产物(AGEs)和 从微血管疾病到骨骼终点以及与年龄相关的骨丢失。最后，目标3将利用体外实验 用股骨标本直接评价成人骨质疏松症患者的股骨成分和生物力学强度 历史悠久的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 利用现有的特征丰富的队列，并招募新的队列进行详细的骨骼表型分析，以 阐明T1D对骨骼健康的影响。我们的研究将为股骨的改变提供新的见解 T1D的骨结构和质量，并将阐明血糖控制和糖尿病并发症对 骨骼的脆弱。该项目的成功完成将为降低老年人骨折风险的战略提供参考 成人T1D。

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.