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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.

项目总结