Bone Quality in Patients with Long-Standing Type 1 Diabetes

摘要 1型糖尿病(T1D)患者的骨折风险是无糖尿病患者的三到六倍 糖尿病，尽管骨密度(BMD)--评估骨质疏松症和骨折的临床标准 风险-与对照组相比，患有T1D的受试者风险较低，仅靠BMD不能解释这种不成比例的 与T1D相关的骨折风险增加。长期低血压的中老年受试者的骨折风险 站立状态的T1D可能与年轻发病的T1D、晚期糖基化末端的积累 由于慢性高血糖或老化和长期T1D的潜在叠加导致的产品(AGEs) 对骨骼的影响。《成人1型糖尿病患者的骨健康》研究(R01DK122554)旨在探讨骨密度 和髋部骨强度的定量计算机断层扫描(QCT)在长期存在的受试者 T1D和年龄、性别和体重指数匹配的对照组，以及调查慢性 高血糖和低血糖对骨骼健康的影响。然而，骨强度-骨骼的主要决定因素 骨折-由骨密度、骨质量及其微环境(包括骨髓脂肪)决定 组织。因此，我们建议对“成人1型糖尿病患者的骨健康”父母进行辅助研究。 研究并利用其具有良好特征的受试者队列、临床、实验室和成像数据来评估 中老年骨质疏松症患者骨髓肥胖症的表型和骨微结构 长期使用的T1D使用先进的成像和图像分析技术。使用化学位移基水- 脂肪分离磁共振成像和高分辨率外周定量计算机断层扫描 (HR-pQCT)我们的目标是评估股骨近端和骨骼24个月BMA变化的差异 中老年慢性骨质疏松症患者桡骨远端和胫骨远端的显微结构 T1D组和非糖尿病对照组。此外，24个月变化的空间分布差异 将使用基于体素的形态计量学来研究两组之间的BMA；以及 具有24个月BMA和骨显微结构变化的慢性高血糖和低血糖也将 探索过了。由于T1D发病率的增加和医疗保健的改善，患有T1D的患者的预期寿命 T1D预计会增加，尽管患有T1D的受试者在 在一生中，大多数骨折发生在老年人，这是一般情况下总的骨折负担最大的时候 人口。因此，迫切需要更好地了解T1D相关骨病的病因，以 制定临床策略以预防临床上和经济上代价高昂的骨折 人口。

ABSTRACT Subjects with type 1 diabetes (T1D) have three- to six-fold higher fracture risk compared with subjects without diabetes, and although bone mineral density (BMD) – the clinical standard to assess osteoporosis and fracture risk – is lower in subjects with T1D compared to controls, BMD alone cannot explain the disproportionate increase in fracture risk associated with T1D. The risk of fracture in middle-age and older subjects with long- standing T1D might be compounded by young-onset T1D, the accumulation of advanced glycation end products (AGEs) due to chronic hyperglycemia, or by a potential superimposition of aging and long-term T1D effects on bone. The “Bone Health in Adults with Type 1 Diabetes” study (R01DK122554) aims to explore BMD and bone strength at the hip using quantitative computed tomography (QCT) in subjects with long-standing T1D and age-, sex- and body mass index-matched controls, as well as to investigate the effects of chronic hyperglycemia and hypoglycemia on bone health. However, bone strength – the main determinant of bone fracture – is determined by BMD, bone quality, and its microenvironment including bone marrow adipose tissue. Therefore, we propose an ancillary study to the “Bone Health in Adults with Type 1 Diabetes” parent study and leverage its well-characterized cohort of subjects, clinical, laboratory, and imaging data to assess phenotypes of bone marrow adiposity (BMA) and bone microstructure in middle-age and older subjects with long-standing T1D using advanced imaging and image analysis techniques. Using chemical shift-based water- fat separation magnetic resonance imaging and high-resolution peripheral quantitative computed tomography (HR-pQCT) we aim to assess differences in 24-month changes in BMA at the proximal femur and in bone microstructure at the distal radius and distal tibia between middle-age and older subjects with long-standing T1D and controls without diabetes. Furthermore, differences in the spatial distribution of 24-month changes in BMA between the two groups will be investigated using voxel-based morphometry; and the associations of chronic hyperglycemia and hypoglycemia with 24-month changes in BMA and bone microstructure will also be explored. Due to the increase incidence of T1D and improved medical care, the life expectancy of subjects with T1D is expected to increase, and although subjects with T1D have an increased risk of fracture during the entire life, most fractures occur at older age when the total fracture burden is greatest in the general population. Therefore, there is a critical need to better understand the etiology of T1D-related bone disorders to develop clinical strategies to prevent clinically and economically costly fractures in this large vulnerable population.