Bone Quality in Patients with Long-Standing Type 1 Diabetes

长期 1 型糖尿病患者的骨质量

• 批准号: 10529985
• 负责人: Julio Carballido-Gamio
• 金额: $ 40.55万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-17 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10529985
• 关键词: Adipose tissue; Adolescence; Adult; Advanced Glycosylation End Products; Age; Aging; Ancillary Study; Body mass index; Bone Density; Bone Diseases; Bone Marrow; Caring; Chemicals; Childhood; Chronic; Clinical; Cross-Sectional Studies; Data; Deterioration; Development; Diabetes Mellitus; Distal; Dual-Energy X-Ray Absorptiometry; Etiology; Fatty acid glycerol esters; Femur; Fracture; General Population; Geometry; Global Change; Hip region structure; Hyperglycemia; Hypoglycemia; Image; Image Analysis; Impairment; Incidence; Insulin-Dependent Diabetes Mellitus; Laboratories; Lead; Life; Life Expectancy; Literature; Magnetic Resonance Imaging; Medical; Obesity; Osteoporosis; Parents; Patients; Peripheral; Persons; Phenotype; Play; Radial; Reporting; Resolution; Risk; Role; Sample Size; Seminal; Site; Spatial Distribution; Techniques; Vertebral column; Vulnerable Populations; Water; X-Ray Computed Tomography; base; bone; bone fragility; bone health; bone loss; bone mass; bone metabolism; bone quality; bone strength; cohort; cortical bone; cost; diabetes control; fracture risk; glycemic control; high risk; improved; insulin dependent diabetes mellitus onset; mechanical properties; middle age; morphometry; novel therapeutics; osteoporosis with pathological fracture; prevent; sex; substantia spongiosa; tibia

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.

抽象的 与没有患 1 型糖尿病 (T1D) 的受试者相比，患有 1 型糖尿病 (T1D) 的受试者的骨折风险高出三到六倍 糖尿病，尽管骨矿物质密度 (BMD) – 评估骨质疏松症和骨折的临床标准 风险 – 与对照组相比，T1D 受试者的风险较低，仅靠 BMD 无法解释不成比例的情况 与 T1D 相关的骨折风险增加。 站立型 T1D 可能与年轻发病的 T1D 混合在一起，即晚期糖基化终末期的积累 由于慢性高血糖或由于衰老和长期 T1D 的潜在叠加而产生的产物 (AGE) “1 型糖尿病成人骨骼健康”研究 (R01DK122554) 旨在探索 BMD 使用定量计算机断层扫描 (QCT) 对长期患有 T1D 和年龄、性别和体重指数匹配的对照，以及研究慢性疾病的影响 高血糖和低血糖对骨骼健康的影响然而，骨强度是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 因此，我们建议对“1 型糖尿病成人骨骼健康”家长进行一项辅助研究。 研究并利用其特征明确的受试者队列、临床、实验室和影像数据来评估 中老年受试者骨髓肥胖（BMA）表型和骨微结构 长期存在的 T1D 使用先进的成像和图像分析技术，使用基于化学位移的水。 脂肪磁分离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中 BMA 24 个月变化的差异 中老年长期患病受试者桡骨远端和胫骨远端的显微结构 T1D 和非糖尿病对照此外，24 个月变化的空间分布存在差异。 将使用基于体素的形态测量法和关联性来研究两组之间的 BMA； 慢性高血糖和低血糖伴随 BMA 和骨微结构 24 个月的变化也将 由于 T1D 发病率的增加和医疗保健的改善，患者的预期寿命有所延长。 T1D 预计会增加，尽管患有 T1D 的受试者在治疗期间骨折的风险增加 在整个一生中，大多数骨折发生在老年，此时骨折总负荷在一般情况下是最大的 因此，迫切需要更好地了解 T1D 相关骨病的病因。 制定临床策略，以防止这一大群弱势群体发生临床和经济上代价高昂的骨折 人口。