Type 2 Diabetes and Bone Health in Youth

2 型糖尿病与青少年骨骼健康

基本信息

批准号：
10650287
负责人：
FIDA BACHA
金额：
$ 18.33万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-20 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10650287
关键词：
Accelerometer Accounting Address Adolescence Adolescent Adult Advanced Glycosylation End Products Adverse effects Affect Age Biochemical Biogenesis Body Composition Bone Density Bone Mineral Contents Bone structure Child Childhood Chronic Chronic Disease Clinical Management Complications of Diabetes Mellitus Cross-Sectional Studies Data Deposition Diabetes Mellitus Diagnosis Distal Dual-Energy X-Ray Absorptiometry Elements Ethnic Origin Evaluation Failure Feasibility Studies Fracture Future Gastrointestinal Hormones Glycosylated hemoglobin A Goals Health Hormonal Hormones Hyperglycemia Hyperinsulinism Impairment In Vitro Individual Insulin Resistance Intervention Intervention Studies Knowledge Life Longevity Longitudinal Studies Measures Mediating Minerals Mitochondria Morphology National Institute of Child Health and Human Development Non-Insulin-Dependent Diabetes Mellitus Nutritional status OGTT Obesity Organ Osteoblasts Osteogenesis Osteoporosis Peripheral Pharmacotherapy Physical activity Pilot Projects Process Public Health Race Research Research Priority Resolution Risk Risk Factors Signal Transduction Structure Testing Translating Weight Weight maintenance regimen X-Ray Computed Tomography Youth bone bone fragility bone health bone mass bone metabolism bone preservation bone quality bone strength bone turnover clinical decision-making design disorder risk early onset experimental study follow-up fracture risk fragility fracture glucose tolerance high risk improved innovation insulin sensitivity lifestyle intervention metabolic phenotype migration negative affect non-diabetic nutrition obesity in children prevent prospective sex skeletal skeletal preservation skeletal tissue tibia

项目摘要

Project Summary Type 2 diabetes (T2D) is associated with lower bone quality and increased risk of fracture in adults. However, it is not known if early onset T2D has adverse effects on bone accrual and strength. The mean age of diagnosis of youth onset T2D is in mid-adolescence, likely influenced by pubertal insulin resistance in obese youth at risk for the disease. Given that bone mineral accrual is occurring in the adolescent years, it is important to understand whether early onset diabetes may be interfering with adequate bone mineral accrual, and the determining factors. It is imperative to address this knowledge gap so that we can institute interventions to prevent and reverse the underlying risk factors, particularly that adverse bone health in childhood may translate to increased risk for osteoporosis and fractures in adult life. The overarching goal of this proposal is to improve bone health in children. The central objective of this application is to determine the effect of youth onset T2D on bone accrual, microstructure and strength, and to understand the factors that may lead to bone fragility in these youth. We hypothesize that hyperglycemia in youth with T2D has a negative effect on bone formation and is associated with low bone turnover, altered bone accrual and microarchitecture. To test this hypothesis, we propose to evaluate volumetric bone mineral density, microarchitecture and strength by finite-element derived parameters (failure load and stiffness) using high resolution peripheral quantitative computed tomography (HRpQCT), and bone turnover markers longitudinally in youth with T2D compared with equally obese youth with normoglycemia and normal weight controls. We will also measure bone mineral content (BMC) and areal bone mineral density (aBMD) using dual energy X-ray absorptiometry (DXA). We will combine these evaluations with careful metabolic phenotyping of body composition by DXA, insulin sensitivity and glycemia (oral glucose tolerance test, HbA1c) and gut hormones that may mediate the effect of diabetes on bone. We will account for the important modulators of bone health including race-ethnicity, sex, pubertal stage, physical activity (by accelerometry), and nutrition status. The study is innovative in elucidating the effects of hyperglycemia on bone accrual and microstructure longitudinally in the adolescent years using HRpQCT, while carefully considering diabetes related factors (diabetes duration, treatment) and other important covariates. We anticipate that we will establish that hyperglycemia in youth with T2D has an adverse impact on bone turnover resulting in lower bone accrual and strength in youth with T2D compared with equally obese youth with normoglycemia and normal weight controls. Our data from this R21 pilot and feasibility experimental study will pave the way for 1) studying lifestyle interventions that target glycemia to improve bone accretion in adolescence, and 2) evaluation the effects of pharmacotherapy on bone health in youth with diabetes to best inform clinical management of these youth.

项目概要 2 型糖尿病 (T2D) 与成人骨质量较低和骨折风险增加有关。然而，它尚不清楚早发性 T2D 是否会对骨生成和强度产生不利影响。平均诊断年龄青少年中 T2D 发病的时间是青春期中期，肥胖青少年中可能受到青春期胰岛素抵抗的影响对于这种疾病。鉴于骨矿物质累积发生在青少年时期，了解这一点很重要早发性糖尿病是否可能干扰足够的骨矿物质积累，以及决定因素。当务之急是解决这一知识差距，以便我们能够采取干预措施来预防和扭转这种情况潜在的风险因素，特别是儿童时期骨骼健康状况不佳可能会增加患骨质疏松症的风险成人生活中的骨质疏松症和骨折。该提案的总体目标是改善骨骼健康孩子们。该应用的中心目标是确定青少年发病的 T2D 对骨生成的影响，微观结构和强度，并了解可能导致这些青少年骨骼脆弱的因素。我们假设年轻 T2D 患者的高血糖对骨形成有负面影响，并且与骨转换率低、骨生成和微结构改变。为了检验这一假设，我们建议评估体积骨矿物质密度、微结构和强度通过有限元导出参数（失效载荷和刚度），使用高分辨率外围定量与患有 T2D 的青少年相比，计算机断层扫描 (HRpQCT) 和骨转换标志物纵向血糖正常且体重控制正常的肥胖青年。我们还将测量骨矿物质含量 (BMC) 和面积骨矿物质密度 (aBMD) 使用双能 X 射线吸收测定法 (DXA)。我们将结合这些评估通过 DXA 对身体成分进行仔细的代谢表型分析、胰岛素敏感性和血糖（口服葡萄糖耐量试验，HbA1c）和肠道激素可能介导糖尿病对健康的影响骨。我们将考虑骨骼健康的重要调节因素，包括种族、性别、青春期、体力活动（通过加速度测量）和营养状况。该研究在阐明高血糖对骨生成和微观结构的影响方面具有创新性使用 HRpQCT 在青少年时期进行纵向研究，同时仔细考虑糖尿病相关因素（糖尿病持续时间、治疗）和其他重要的协变量。我们预计我们将建立患有 T2D 的青少年的高血糖会对骨转换产生不利影响，导致骨生成降低，患有 T2D 的青少年的力量与血糖正常且体重控制正常的同等肥胖青少年相比。我们从 R21 试点和可行性实验研究中获得的数据将为 1) 研究生活方式铺平道路以血糖为目标的干预措施，以改善青春期骨质增生，以及 2) 评估以下措施的效果对患有糖尿病的青少年进行骨骼健康的药物治疗，以便为这些青少年的临床管理提供最佳信息。