Determinants of bone microarchitectural compromise in youth with type 1 diabetes

1 型糖尿病青少年骨微结构受损的决定因素

• 批准号: 10693855
• 负责人: MARY L BOUXSEIN
• 金额: $ 30.02万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10693855
• 关键词: 16 year old; 20 year old; Acceleration; Accelerometer; Address; Adolescence; Adolescent; Adoption; Adult; Affect; Age; Aging; Animal Model; Attenuated; Automobile Driving; Biomechanics; Blood Glucose; Bone Density; Bone Development; Child; Childhood; Childhood diabetes; Clinical; Clinical Data; Continuous Glucose Monitor; Data; Development; Diabetes Mellitus; Dual-Energy X-Ray Absorptiometry; Elderly; Enrollment; Etiology; Failure; Foundations; Fracture; Future; General Population; Generations; Geometry; Glucose; Glycosylated hemoglobin A; Goals; Growth; Hip Fractures; Hyperglycemia; Imaging technology; Impairment; Incidence; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; International; Intervention Studies; Knowledge; Life; Life Expectancy; Measures; Modeling; Morbidity - disease rate; Morphology; Observational Study; Osteogenesis; Outcome; Patients; Peripheral; Persons; Phenotype; Physical activity; Physical assessment; Physiological; Population; Populations at Risk; Prevention; Prevention strategy; Principal Investigator; Process; Puberty; Public Health; Questionnaires; Race; Research; Resolution; Risk; Skeletal Development; Skeleton; Structure; Systems Development; Technology; Testing; Therapeutic Intervention; Time; Visit; X-Ray Computed Tomography; Youth; age group; aged; bone; bone mass; bone metabolism; bone strength; bone turnover; boys; comparison control; critical period; density; diabetes risk; diabetic; effective therapy; fracture risk; fragility fracture; girls; glycemic control; improved; mechanical load; moderate-to-vigorous physical activity; mortality; non-diabetic; osteoporosis with pathological fracture; peer; prepuberty; prevent; prospective; response; sex; skeletal; skeletal injury; substantia spongiosa; targeted treatment; young adult

PROJECT SUMMARY/ABSTRACT The risk of fracture, particularly hip fracture, among people with type 1 diabetes (T1D) is 3 to 6-fold higher than that of the general population. The increased risk of fracture starts as early as the first decade of life, suggesting that T1D affects bone development in childhood. This is not surprising: childhood and adolescence are critical periods for the development of the skeletal system, characterized by exuberant bone formation. Approximately 90% of the adult skeleton is formed by late adolescence; therefore, a process that interferes with bone formation in childhood has the potential to lead to profound and life-long effects. However, the specific insults to the skeleton that predispose patients with T1D to fracture and the mechanisms underlying these insults remain poorly understood. T1D-associated skeletal fragility is becoming an increasingly important public health problem. With a rising incidence of T1D in the population as well as improvements in life expectancy among patients with T1D due to improved treatment options, a larger number of T1D patients are aging and will be at risk for diabetes-associated fragility fracture, conferring substantial morbidity and mortality. The overall goal of this 2-year prospective observational study is to define the differences in bone development and the factors that cause these differences in children and young adults with T1D ages 6-20 years compared to their non-diabetic peers. Our preliminary data in pubertal girls demonstrate that trabecular bone density is low and trabecular bone morphology is altered in T1D, and that those children with higher average blood glucose as measured by HbA1c are more severely affected. In Aim 1, we will identify differences in bone mass, microarchitecture, and strength in both boys and girls across the age spectrum of childhood to young adulthood using second-generation high-resolution peripheral quantitative computed tomography. In Aim 2, we will determine which glycemic parameters predict altered bone mass, microarchitecture, and strength using continuous glucose monitoring to measure average glycemia, hyperglycemic time, and glucose variability. In Aim 3, we will use validated questionnaires assessing bone loading activities as well as accelerometry to determine to what extent the bone-forming response to physical activity is blunted in T1D. The Co-Principal Investigators, Drs. Deborah Mitchell, Madhusmita Misra, and Mary Bouxsein, have complementary clinical and research expertise in T1D, bone metabolism, and bone biomechanics. Data derived from this study will provide critical knowledge about the specific bone alterations in T1D and their underlying mechanisms to enable the development of targeted and effective therapies to prevent fragility fracture in this at-risk population.

项目摘要/摘要 在1型糖尿病(T1D)患者中，骨折的风险，特别是髋部骨折，比 这是普通民众的问题。骨折风险的增加早在生命的第一个十年就开始了， 提示T1D影响儿童时期的骨骼发育。这并不令人惊讶：童年和青春期 是骨骼系统发育的关键时期，以旺盛的骨形成为特征。 大约90%的成人骨骼是在青春期后期形成的；因此，这一过程干扰了 儿童时期的骨骼形成有可能导致深远的终生影响。然而， 对骨骼的特殊侮辱使T1D患者容易骨折及其机制 人们对这些侮辱仍然知之甚少。与T1D相关的骨骼脆性正变得越来越重要 公共卫生问题。随着T1D在人群中的发病率上升以及生活的改善 由于治疗方法的改进，T1D患者中的预期人数较多 并且会面临糖尿病相关的脆性骨折的风险，从而导致大量的发病率和死亡率。 这项为期两年的前瞻性观察研究的总体目标是确定骨骼发育的差异。 而导致这些差异的因素在6-20岁的儿童和年轻人中进行了比较 给他们的非糖尿病同龄人。我们在青春期女孩中的初步数据表明，骨小梁密度是 低骨小梁形态在T1D时改变，平均血流量较高的儿童 糖化血红蛋白测得的血糖受到的影响更严重。在目标1中，我们将确定骨量的差异， 微建筑，以及从童年到青年的男孩和女孩的力量 成年后使用第二代高分辨率外周定量计算机断层扫描。在目标2中，我们 将确定哪些血糖参数可以预测骨量、微结构和强度的改变 持续监测血糖以测量平均血糖、高血糖时间和血糖变异性。在……里面 目标3，我们将使用有效的问卷评估骨负荷活动以及加速度计来 确定在T1D中，对体力活动的成骨反应减弱到什么程度。联席校长 研究人员，黛博拉·米切尔博士、马德斯米塔·米斯拉博士和玛丽·布克塞恩博士，有互补的临床和 在T1D、骨代谢和骨生物力学方面的研究专长。从这项研究中得出的数据将提供 关于T1D的特定骨骼改变及其潜在机制的关键知识 开发有针对性和有效的治疗方法，预防高危人群中的脆性骨折。