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.

项目摘要/摘要 1型糖尿病(T1D)与从童年开始并延伸的骨折风险增加有关 在整个生命周期内。T1D骨骼脆性增加的病理生理机制尚不清楚， 目前还没有筛查或治疗指南来帮助医生照顾这些患者的骨骼健康。 这位候选人收集的初步数据表明，患有T1D的青少年钙含量下降 在骨骼的关键年份，由于过量的尿钙丢失，骨沉积的有效性 矿产应计利润。这本K23中概述的研究指导了以患者为导向的研究生涯发展 旨在检验尿钙排泄过量是一种潜在的 T1D青少年骨矿物质积累受损的目标贡献者。建议进行的研究及 职业发展计划将直接支持候选人成为一名独立医生的目标- 致力于促进对T1D和其他慢性病影响的科学理解的科学家 并将这些见解应用于改善临床护理。这些目标将在整个课程中向前推进 通过完成以下职业发展目标获得K23奖：(1)获得技术和 在骨健康领域进行高水平的以病人为导向的研究所需的教学知识。在……下面 在导师奥布莱恩博士的指导下，候选人将学习如何使用STRATE进行临床研究 同位素。这将包括指导研究设计和实施、样本准备和分析以及数据 建模和解释。此外，他还将完成临床试验设计方面的课程，以增强他的 之前的临床流行病学培训，并将这一知识应用于一项初步研究，以调查氯苯吡酮作为一种 T1D相关性高钙尿症的潜在治疗。(2)获得评估和管理方面的专业知识 儿童骨病患者。这将通过提供儿科骨的临床护理来实现 健康诊所，在使用DXA评估骨积累方面获得专业知识，并在 高钙尿症的评估和治疗。(3)向临床研究人员的独立过渡。这个 候选人组建了一支导师和顾问团队，他们都是本网站相关内容领域的专家 并建立了获得NIH资金和指导年轻调查人员的记录。他们会 监督他在完成拟议的研究、在全国会议上提出工作并申请 用于后续的辅助和R01赠款。总而言之，拟议的项目利用了广泛的资源 以及从该领域的专家那里学习如何进行稳定同位素研究的独特机会 目的探讨T1D的一个重要临床并发症。这些研究的结果，连同 职业发展活动，为候选人提供一条明确的途径，以获得独立的资金 研究改善T1D患者骨健康的临床干预措施。