Type 2 Diabetes and Bone Health in Youth

2 型糖尿病与青少年骨骼健康

• 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
• 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

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.

项目摘要 2型糖尿病（T2D）与成人骨质质量较低和骨折风险增加有关。但是，它 尚不清楚早期发作T2D是否对骨骼和强度产生不利影响。诊断的平均年龄 青年发病的T2D处于青春期，可能受到肥胖青年的青春期胰岛素抵抗的影响 为了疾病。鉴于在青少年时期发生骨矿物质应计，因此重要的是要了解 早期发作糖尿病是否可能干扰适当的骨矿物质应计和决定因素。 必须解决这一知识差距，以便我们可以采取干预措施来预防和扭转 潜在的危险因素，尤其是儿童时期不良骨骼健康可能会转化为增加的风险 成人生活中的骨质疏松和骨折。该提案的总体目标是改善骨骼健康 孩子们。该应用的核心目的是确定青年发作T2D对骨骼应计的影响， 微观结构和力量，并了解可能导致这些年轻人骨骼脆弱的因素。我们 假设T2D青年中的高血糖对骨形成有负面影响，并且与 骨转换率低，骨骼应计和微体系结构改变。 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 使用高分辨率外周定量的有限元元素衍生参数（故障负载和刚度） 与T2D青年相比 同样肥胖的年轻人患有正常血糖和正常体重控制。我们还将测量骨矿物质含量 使用双能X射线吸收仪（DXA）（BMC）和面骨矿物质密度（ABMD）。我们将结合 通过DXA对身体组成的仔细代谢表型的评估，胰岛素敏感性和 血糖（口服葡萄糖耐量测试，HBA1C）和肠激素，可能介导糖尿病对糖尿病的影响 骨。我们将考虑骨骼健康的重要调节剂，包括种族种族，性别，青春期阶段， 体育活动（通过加速度计）和营养状况。 该研究在阐明高血糖对骨骼和微观结构的影响方面具有创新性 在青少年时期使用HRPQCT纵向，同时仔细考虑了与糖尿病相关的因素 （糖尿病持续时间，治疗）和其他重要的协变量。我们预计我们将确定 T2D青年的高血糖对骨转换的不利影响，导致骨骼降低和 与同样肥胖的年轻人相比，患有T2D的青年的力量与患有正常血糖和正常体重控制的年轻人相比。 我们来自R21飞行员和可行性实验研究的数据将为1）研究生活方式铺平道路 靶向血糖以改善青春期骨积聚的干预措施，以及2）评估 糖尿病青年骨骼健康的药物治疗，以最好地为这些青年的临床管理提供信息。