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: 10017184
• 负责人: MARY L BOUXSEIN
• 金额: $ 29.73万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017184
• 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

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.

项目总结/摘要 1型糖尿病（T1 D）患者发生骨折（尤其是髋部骨折）的风险是普通糖尿病患者的3至6倍。 即一般民众的权利。骨折风险的增加早在生命的第一个十年就开始了， 这表明T1 D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，其特征是骨形成旺盛。 大约90%的成人骨骼是在青春期后期形成的;因此， 在儿童时期对骨骼形成的影响有可能导致深远的终身影响。但 使T1 D患者易于骨折的骨骼特异性损伤及其潜在机制 人们对这些侮辱仍知之甚少。T1 D相关的骨骼脆弱性正变得越来越重要， 公共卫生问题。随着人群中T1 D发病率的上升以及生活的改善 由于治疗选择的改善，T1 D患者的预期， 并且将处于糖尿病相关的脆性骨折的风险中，从而导致显著的发病率和死亡率。 这项为期2年的前瞻性观察性研究的总体目标是确定骨发育的差异 以及导致6-20岁T1 D儿童和年轻人出现这些差异的因素， 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， T1 D患者的低骨密度和骨小梁形态发生改变， 通过HbA 1c测量的葡萄糖受到更严重的影响。在目标1中，我们将确定骨量的差异， 微结构，以及从童年到年轻的男孩和女孩的力量 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， 将确定哪些血糖参数预测改变的骨量，微结构和力量， 连续血糖监测，以测量平均血糖、高血糖时间和血糖变异性。在 目标3，我们将使用有效的问卷评估骨负荷活动以及加速度计， 确定T1 D患者对体力活动的骨形成反应减弱的程度。联合校长 研究人员Deborah Mitchell博士、Madhusmita Misra博士和玛丽Bouxsein博士具有互补的临床和 T1 D、骨代谢和骨生物力学方面的研究专长。本研究的数据将提供 关于T1 D中特定骨改变及其潜在机制的关键知识， 开发有针对性的有效疗法，以预防这一高危人群的脆性骨折。