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.

项目概要/摘要 1 型糖尿病 (T1D) 患者发生骨折（尤其是髋部骨折）的风险比其他患者高 3 至 6 倍普通民众的情况。骨折风险早在生命的第一个十年就开始增加，表明 T1D 会影响儿童时期的骨骼发育。这并不奇怪：童年和青春期是骨骼系统发育的关键时期，其特点是骨形成旺盛。大约90%的成人骨骼是在青春期后期形成的；因此，一个干扰的过程儿童时期的骨骼形成有可能产生深远的终生影响。然而，导致 1 型糖尿病患者骨折的特定骨骼损伤及其潜在机制人们对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。随着人口中 T1D 发病率的上升以及生活的改善由于治疗选择的改善，1型糖尿病患者的预期增加，更多的1型糖尿病患者衰老，并面临与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 2 年的前瞻性观察研究的总体目标是确定骨骼发育的差异以及导致 6-20 岁 T1D 儿童和年轻人出现这些差异的因素给他们的非糖尿病同龄人。我们对青春期女孩的初步数据表明，骨小梁密度 T1D 中低骨和小梁骨形态发生改变，平均血液水平较高的儿童 HbA1c 测量的血糖受到更严重的影响。在目标 1 中，我们将确定骨量的差异，从儿童到青年年龄段的男孩和女孩的微结构和力量成年期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，我们将使用以下方法确定哪些血糖参数可预测骨量、微结构和强度的改变连续血糖监测可测量平均血糖、高血糖时间和血糖变异性。在目标 3，我们将使用经过验证的问卷来评估骨负荷活动以及加速度测量确定 T1D 中体力活动的骨形成反应减弱的程度。联合校长研究人员，博士。 Deborah Mitchell、Madhusmita Misra 和 Mary Bouxsein 具有互补的临床和 T1D、骨代谢和骨生物力学方面的研究专业知识。从这项研究中获得的数据将提供关于 T1D 特定骨骼改变及其潜在机制的关键知识，使开发有针对性的有效疗法来预防这一高危人群的脆性骨折。