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

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.