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

基本信息

批准号：
10206857
负责人：
MARY L BOUXSEIN
金额：
$ 25.21万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-12 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10206857
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 Data Clinical Research 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 Lead Life Life Expectancy Measures Modeling Morbidity - disease rate Morphology Observational Study Osteogenesis Outcome Patients Peripheral 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 critical period density diabetes control diabetes risk diabetic effective therapy fracture risk fragility fracture girls glucose monitor 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

项目摘要

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 1型糖尿病患者（T1D）中骨折的风险，尤其是髋部骨折的风险，比普通人群。骨折风险的增加早在生命的头十年就开始了表明T1D会影响童年的骨骼发育。这不足为奇：童年和青春期是骨骼系统发展的关键时期，其特征是骨骼形成。大约90％的成年骨骼是由青春期晚期形成的。因此，一个干扰的过程童年时期的骨骼形成有可能导致深远而终生的影响。但是，对骨骼的特定侮辱，使T1D患者易患骨折的骨骼和骨骼的机制这些侮辱仍然知之甚少。 T1D相关的骨骼脆弱性变得越来越重要公共卫生问题。人口中T1D发病率上升以及生活的改善由于治疗方案的改善，患有T1D患者的预期见名，T1D患者数量越大衰老，将有糖尿病相关脆性骨折的风险，赋予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定义骨骼发育的差异以及T1D年龄在6 - 20岁的儿童和年轻人中引起这些差异的因素到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，小梁骨密度是 T1D中的低和小梁骨形态发生了变化，那些平均血液较高的儿童通过HBA1C测量的葡萄糖受到更严重的影响。在AIM 1中，我们将确定骨量的差异，童年时代的男孩和女孩的微观结构和力量使用第二代高分辨率外围定量计算机断层扫描的成年。在AIM 2中，我们将确定哪些血糖参数可以预测骨骼质量，微体系结构和强度的改变连续葡萄糖监测以测量平均血糖，高血糖时间和葡萄糖变异性。在 AIM 3，我们将使用评估骨负荷活动的经过验证的问卷以及加速度测定法在T1D中确定对体育活动的骨形成反应在多大程度上被钝化。联合主持人调查人员，博士。 Deborah Mitchell，Madhusmita Misra和Mary Bouxsein拥有互补的临床和 T1D，骨代谢和骨生物力学方面的研究专业知识。从这项研究得出的数据将提供关于T1D及其基本机制的特定骨骼改变的批判性知识，以使开发有效且有效的疗法，以防止这种高危人群中的脆弱性骨折。