Investigation of Hypercalciuria as a Cause of Impaired Bone Mineral Accrual in Type 1 Diabetes

高钙尿症作为 1 型糖尿病骨矿物质累积受损原因的调查

• 批准号: 9370203
• 负责人: David R Weber
• 金额: $ 19.2万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9370203
• 关键词: Adolescence; Adolescent; Adverse effects; Adverse event; Affect; Age; Alkaline Phosphatase; Area; Biochemical Markers; Blood specimen; Bone Density; Bone Diseases; Bone Mineral Contents; Bone structure; Calcium; Calcium Isotopes; Caring; Childhood; Chlorthalidone; Chronic; Chronic Disease; Clinic; Clinical; Clinical Investigator; Clinical Research; Clinical Trials Design; Collagen; Collection; Complication; Data; Data Analyses; Densitometry; Deposition; Development Plans; Diabetes Mellitus; Diagnosis; Diet Records; Disease; Diuretics; Dual-Energy X-Ray Absorptiometry; Electrolytes; Environment; Equilibrium; Evaluation; Fasting; Female Adolescents; Fracture; Functional disorder; Funding; Future; Glycosylated hemoglobin A; Goals; Grant; Growth; Guidelines; Hip Fractures; Home environment; Hour; Hyperglycemia; Impairment; Injury; Instruction; Insulin-Dependent Diabetes Mellitus; Intervention; Investigation; Isotopes; Kinetics; Knowledge; Learning; Longevity; Longitudinal cohort study; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Minerals; Modeling; Morbidity - disease rate; Oral; Osteogenesis; Outcome; Participant; Patients; Phenotype; Physicians; Pilot Projects; Population; Preparation; Public Health; Race; Records; Research Design; Research Personnel; Resources; Risk; Risk Factors; Safety; Sampling; Scientific Advances and Accomplishments; Scientist; Secure; Serum; Site; Skeleton; Spottings; Techniques; Testing; Time; Training; United States National Institutes of Health; Urine; Work; bone; bone health; bone quality; bone turnover; calcium absorption; calcium excretion; calcium intake; calcium metabolism; career development; clinical care; clinical epidemiology; cohort; critical period; crosslink; data modeling; design; fracture risk; glycemic control; hypercalciuria; improved; insight; meetings; mortality; novel; patient oriented research; primary outcome; renal calcium; screening; sex; skeletal; stable isotope; therapy design; thiazide; urinary

PROJECT SUMMARY/ABSTRACT Type 1 diabetes (T1D) is associated with an increased risk of fracture that begins in childhood and extends across the lifespan. The pathophysiology underlying the increased skeletal fragility in T1D is not known, and there are no screening or treatment guidelines to aid practitioners caring for the bone health of these patients. The candidate has collected preliminary data suggesting that adolescents with T1D have decreased calcium availability for bone deposition as a result of excess urinary calcium loss during the critical years for bone mineral accrual. The studies outlined in this K23 Mentored Patient-Oriented Research Career Development Award are designed to test the central hypothesis that excess urinary calcium excretion is a potentially targetable contributor to impaired bone mineral accrual in adolescents with T1D. The proposed studies and career development plan will directly support the candidate's goals of becoming an independent physician- scientist working to advance the scientific understanding of the effects of T1D and other chronic disease on bone health and applying these insights to improve clinical care. These goals will be advanced over the course of the K23 award by completion of the following career development objectives: (1) Acquire the technical and didactic knowledge necessary to conduct high-level patient-oriented research in the field of bone health. Under the direction of mentor Dr. O'Brien, the candidate will learn how to perform clinical studies using stable isotopes. This will include instruction in study design and conduct, sample preparation and analysis, and data modeling and interpretation. Additionally, he will complete coursework in clinical trial design to augment his prior training in clinical epidemiology and apply this knowledge in a pilot study to investigate chlorthalidone as a potential treatment for T1D related hypercalciuria. (2) Gain expertise in the evaluation and management of patients with pediatric bone disease. This will be accomplished by providing clinical care in Pediatric Bone Health Clinic, gaining expertise in the use of DXA to evaluate bone accrual, and gaining expertise in the evaluation and treatment of hypercalciuria. (3) Transition to independence as a clinical investigator. The candidate has assembled a team of mentors and advisors who are expert in the relevant content areas of this proposal and have established records of securing NIH funding and mentoring young investigators. They will oversee his progress as he completes the proposed studies, presents work at national meetings, and applies for subsequent ancillary and R01 grants. In summary, the proposed project leverages the extensive resources of URMC and the unique opportunity to learn how to perform stable isotope studies from an expert in the field to investigate an important clinical complication of T1D. The results of these studies, in-conjunction with the career development activities, provide a clear path for the candidate to secure independent funding to investigate clinical interventions to improve bone health in T1D.

项目概要/摘要 1 型糖尿病 (T1D) 与骨折风险增加相关，骨折风险从儿童期开始，并会延长 贯穿整个生命周期。 T1D 骨骼脆性增加的病理生理学尚不清楚，并且 没有筛查或治疗指南来帮助从业者照顾这些患者的骨骼健康。 候选人收集的初步数据表明患有 T1D 的青少年钙含量下降 在骨骼生长的关键年份，由于尿钙流失过多，导致骨沉积的可用性 矿物应计。本 K23 指导的以患者为导向的研究职业发展中概述的研究 该奖项旨在检验一个中心假设，即尿钙排泄过多可能是一种潜在的疾病。 导致 1 型糖尿病青少年骨矿物质累积受损的目标因素。拟议的研究和 职业发展计划将直接支持候选人成为独立医生的目标- 科学家致力于推进对 T1D 和其他慢性疾病对健康影响的科学认识 骨骼健康并应用这些见解来改善临床护理。这些目标将在课程中不断推进 通过完成以下职业发展目标获得 K23 奖： (1) 获得技术和 在骨骼健康领域进行高水平的以患者为导向的研究所需的教学知识。在下面 在导师O'Brien博士的指导下，候选人将学习如何使用稳定的药物进行临床研究 同位素。这将包括研究设计和实施、样品制备和分析以及数据方面的指导 建模和解释。此外，他将完成临床试验设计课程，以增强他的能力 事先接受过临床流行病学培训，并将这些知识应用于试点研究，以调查氯噻酮作为 T1D 相关高钙尿症的潜在治疗方法。 (2) 获得评估和管理方面的专业知识 小儿骨病患者。这将通过提供儿科骨科临床护理来实现 健康诊所，获得使用 DXA 评估骨生成的专业知识，并获得以下方面的专业知识 高钙尿症的评估和治疗。 (3) 过渡为独立临床研究者。这 候选人组建了一个由导师和顾问组成的团队，他们是该领域相关内容领域的专家 提案并建立了获得 NIH 资金和指导年轻研究人员的记录。他们会 监督他完成拟议研究、在全国会议上展示工作并申请的进展 用于后续辅助和 R01 赠款。总之，拟议的项目利用了广泛的资源 URMC 的课程以及向该领域专家学习如何进行稳定同位素研究的独特机会 调查 T1D 的重要临床并发症。这些研究的结果，结合 职业发展活动，为候选人获得独立资金提供明确的途径 研究改善 1 型糖尿病骨骼健康的临床干预措施。