Bone Quality in Patients with Long-Standing Type 1 Diabetes

摘要 1型糖尿病（T1 D）受试者的骨折风险是未患T1 D的受试者的3 - 6倍。 虽然骨矿物质密度（BMD）是评估骨质疏松症和骨折的临床标准， 风险-与对照组相比，T1 D受试者的BMD较低，单独的BMD不能解释不成比例的 与T1 D相关的骨折风险增加。在中老年人群中，骨折的风险是长期的， 持续性T1 D可能会与非持续性T1 D复合，晚期糖基化终末产物的积累 由于慢性高血糖症，或由于衰老和长期T1 D的潜在叠加， 对骨骼的影响“1型糖尿病成人的骨健康”研究（R 01 DK 122554）旨在探索BMD 使用定量计算机断层扫描（QCT）在长期患有骨质疏松症的受试者中测量髋关节和骨强度 T1 D和年龄、性别和体重指数匹配的对照，以及研究慢性 高血糖和低血糖对骨骼健康的影响。然而，骨骼强度-骨骼的主要决定因素 骨折-由BMD、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“1型糖尿病成人的骨骼健康”进行一项辅助研究。 研究并利用其特征明确的受试者队列、临床、实验室和成像数据来评估 骨髓肥胖（BMA）表型和骨显微结构在中年和老年人受试者， 使用先进的成像和图像分析技术来治疗长期存在的T1 D。利用化学位移的水- 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）我们旨在评估股骨近端和骨中BMA 24个月变化的差异 中老年人桡骨远端和胫骨远端的微结构 T1 D和无糖尿病的对照组。此外，24个月变化的空间分布差异， 两组之间的BMA将使用基于体素的形态测量进行研究; 慢性高血糖症和低血糖症伴24个月BMA和骨微结构变化， 探讨了由于T1 D发病率的增加和医疗保健的改善， T1 D预计会增加，尽管T1 D受试者在治疗期间骨折风险增加， 在整个生命中，大多数骨折发生在老年，一般来说， 人口因此，迫切需要更好地了解T1 D相关骨病的病因， 制定临床策略，以防止在这个大型脆弱的临床和经济昂贵的骨折 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.