Bone marrow fat and skeletal health in type 2 diabetes
2 型糖尿病患者的骨髓脂肪和骨骼健康
基本信息
- 批准号:9891879
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdipocytesAffectAntidiabetic DrugsBehaviorBiometryBone DensityBone DiseasesBone MarrowCaringCell CountClinical InvestigatorClinical ResearchComplicationComplications of Diabetes MellitusDataDeath RateDiabetes MellitusDifferentiated GeneDual-Energy X-Ray AbsorptiometryEnrollmentEpidemiologyFatty acid glycerol estersFlow CytometryFractureFracture HealingFundingFutureGastric BypassGene ExpressionGlycosylated hemoglobin AGoalsHealthHealthcareHip FracturesImpairmentIndividualInvestigationK-Series Research Career ProgramsLeadLinkMagnetic Resonance SpectroscopyMarrowMeasuresMedicalMedical Care CostsMentorsMentorshipMesenchymal Stem CellsMetabolicMetabolismMethodsNon-Insulin-Dependent Diabetes MellitusOrganOsteoblastsOsteogenesisOsteoporosisOutcomePathogenesisPathogenicityPathway interactionsPeripheralPeripheral Blood Mononuclear CellPhysiciansPlayPorosityPositioning AttributePostoperative ComplicationsPostoperative PeriodPrevalencePreventiveProspective StudiesProspective cohort studyRadialRadiology SpecialtyReportingResearchResearch DesignResearch PersonnelResearch TrainingResolutionRoleSerumShapesSiteSkeletonTherapeuticTrabecular Bone ScoreTrainingUnsaturated FatsVeteransX-Ray Computed Tomographyadult obesitybariatric surgerybonebone healthbone imagingbone massbone qualitybone turnoverdesigndiabetic bone diseaseeconomic costeffective therapyexperiencefallsfracture riskglycemic controlhealth administrationhigh riskimaging modalityimprovedinsightlaboratory experiencelipid biosynthesislipid metabolismmortality risknegative affectnovelosteoblast differentiationpreservationprogenitorprogramsskeletalskillsspine bone structurestem cellstibia
项目摘要
Dr. Kim’s long-term goal is to be a VA physician investigator, elucidating mechanisms of diabetic bone
disease in order to reduce fracture risk in people with diabetes. There is growing recognition that bone disease
is a complication of type 2 diabetes mellitus (T2DM). In T2DM, hip fracture risk is increased by more than a
third, and after fracture, individuals with T2DM have higher rates of postoperative complications and a higher
risk of mortality. Fracture risk is elevated even after controlling for falls, and hip fractures occur despite
preserved or higher bone mineral density (BMD). The fat within the bone marrow is proposed to play a
pathogenic role in diabetic bone disease, as fat and bone are intimately related within the marrow
microenvironment. Adipocytes and osteoblasts share a common mesenchymal stem cell precursor, and
adipogenesis could occur at the expense of osteoblastogenesis. Indeed, greater levels of marrow fat content
are associated with lower BMD and higher fracture risk. However, it is unknown whether marrow fat can be
manipulated to improve diabetic bone disease. Hemoglobin A1c (HbA1c) positively correlates with higher
levels of marrow fat, so enhanced glycemic control might normalize marrow fat and improve bone outcomes.
Given the widespread prevalence of diabetes and the medical and economic costs of fractures, there is an
urgent need to understand diabetic bone disease to identify targeted preventive and therapeutic strategies.
During the Career Development Award-2 (CDA-2) period, Dr. Kim’s goal is to acquire the training and
implement the studies needed to understand the effects of improved glycemic control on marrow fat and bone
health. She will gain expertise in valuable clinical research and translational methods that will position her to
become a leader in the field of diabetic bone disease. Dr. Kim will enroll and follow 75 Veterans with poorly
controlled T2DM (HbA1c 8.5-12.0%) who are working with their clinicians to improve glycemic control. She will
determine the effects of improved glycemic control on bone marrow fat (Aim 1) and the relationship between
changes in marrow fat with bone quality and mass (Aim 2). Pursuit of these aims will involve critical training in
the design and implementation of a prospective cohort study. Dr. Kim will use advanced and sensitive imaging
modalities (including magnetic resonance spectroscopy, high-resolution peripheral quantitative computed
tomography) to assess marrow fat and bone outcomes at baseline and then after 1 year of intensified medical
management. Dr. Kim will also use cutting edge translational methods to explore the role of osteoblast
differentiation as a pathway linking marrow fat and bone outcomes (Aim 3). This will include characterizing
circulating osteoblast progenitor cells by flow cytometry and evaluating expression of osteoblast differentiation
genes. Training in advanced diabetes and lipid metabolism will allow Dr. Kim to interpret these findings and
gain important insights into the pathogenesis of diabetic bone disease. This research is expected to advance
understanding of marrow fat behavior, which may lead to targeted preventive and therapeutic strategies for
diabetic bone disease and osteoporosis. Dr. Kim has assembled a diverse mentorship team comprised of
experts in osteoporosis, metabolism, epidemiology, biostatistics, and radiology. Her training will involve a
combination of individual tutorials with her mentors and scientific advisors, hands-on experience, and formal
coursework. The proposed research will provide Dr. Kim with preliminary data for a larger and longer-term
prospective study of diabetic bone disease, which she will propose in a Merit Review application submitted
before the end of the CDA-2 period. Dr. Kim is committed to improving the health care of Veterans through
clinical research, and with her proposed research and training, she will develop a thriving research program at
the VA.
金博士的长期目标是成为一名退伍军人事务部内科研究员,阐明糖尿病骨骼的发病机制
以降低糖尿病患者的骨折风险。越来越多的人认识到骨病
是2型糖尿病(T2 DM)的并发症。在T2 DM患者中,髋部骨折的风险增加超过1
第三,在骨折后,T2 DM患者的术后并发症发生率更高,
死亡的风险。即使在控制跌倒之后,骨折风险也会增加,尽管
保持或更高的骨密度(BMD)。骨髓中的脂肪被认为是一种
在糖尿病骨疾病中的致病作用,因为脂肪和骨骼在骨髓中密切相关
微环境。脂肪细胞和成骨细胞共享共同的间充质干细胞前体,并且
脂肪生成可能以成骨细胞生成为代价。事实上,骨髓脂肪含量更高
与较低的骨密度和较高的骨折风险有关。然而,目前尚不清楚骨髓脂肪能否
被操纵以改善糖尿病骨骼疾病。血红蛋白A1c(HbA1c)与
骨髓脂肪水平,因此加强血糖控制可能会使骨髓脂肪正常化,并改善骨骼结果。
鉴于糖尿病的广泛流行以及骨折的医疗和经济成本,
迫切需要了解糖尿病骨疾病,以确定有针对性的预防和治疗策略。
在职业发展奖-2(CDA-2)期间,金博士的目标是获得培训和
实施必要的研究,以了解改善血糖控制对骨髓脂肪和骨骼的影响
健康。她将获得宝贵的临床研究和翻译方法方面的专业知识,这将使她
成为糖尿病骨病领域的领先者。金博士将招收并跟踪75名退伍军人
受控的T2 DM(HbA1c 8.5-12.0%),他们正在与临床医生合作改善血糖控制。她会的
确定改善血糖控制对骨髓脂肪的影响(目标1)及其与
骨髓脂肪随骨质量和骨量的变化(目标2)。追求这些目标将涉及关键的培训
前瞻性队列研究的设计和实施。金博士将使用先进和灵敏的成像技术
模式(包括磁共振波谱、高分辨率外设定量计算
体层摄影术)以评估基线和强化治疗一年后的骨髓脂肪和骨骼结果
管理层。金博士还将使用尖端的翻译方法来探索成骨细胞的作用
分化作为连接骨髓脂肪和骨结果的途径(目标3)。这将包括刻画
流式细胞术检测成骨细胞前体细胞及其在成骨细胞分化中的表达
基因。高级糖尿病和脂代谢方面的培训将使金博士能够解释这些发现并
获得对糖尿病骨病发病机制的重要见解。这项研究有望取得进展
了解骨髓脂肪的行为,这可能导致有针对性的预防和治疗策略
糖尿病骨病和骨质疏松症。金博士组建了一个多元化的导师团队,成员包括
骨质疏松症、新陈代谢、流行病学、生物统计学和放射学专家。她的培训将包括
与她的导师和科学顾问的个人教程、实践经验和正式教程相结合
课程作业。这项拟议的研究将为金博士提供更大、更长期的初步数据
糖尿病骨疾病的前瞻性研究,她将在提交的功绩审查申请中提出这项研究
在CDA-2期间结束之前。金博士致力于通过以下方式改善退伍军人的医疗保健
临床研究,以及她提议的研究和培训,她将在
退伍军人事务部。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Tiffany Youngun Kim其他文献
Tiffany Youngun Kim的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Tiffany Youngun Kim', 18)}}的其他基金
Bone marrow fat and skeletal health in type 2 diabetes
2 型糖尿病患者的骨髓脂肪和骨骼健康
- 批准号:
10413813 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Bone marrow fat and skeletal health in type 2 diabetes
2 型糖尿病患者的骨髓脂肪和骨骼健康
- 批准号:
10657381 - 财政年份:2020
- 资助金额:
-- - 项目类别:
相似国自然基金
支链氨基酸代谢紊乱调控“Adipocytes - Macrophages Crosstalk”诱发2型糖尿病脂肪组织功能和结构障碍的作用及机制
- 批准号:81970721
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
相似海外基金
New development of cellular regeneration therapy in jaw bone using stem cells derived from adipocytes jaw bone
利用颌骨脂肪细胞来源的干细胞进行颌骨细胞再生治疗的新进展
- 批准号:
23K16058 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
A novel mechanism of insulin resistance mediated by uric acid metabolism in adipocytes
脂肪细胞尿酸代谢介导胰岛素抵抗的新机制
- 批准号:
23K10969 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Hypertrophic adipocytes as biophysical mediators of breast cancer progression
肥大脂肪细胞作为乳腺癌进展的生物物理介质
- 批准号:
10751284 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Development of adipocytes for gene therapy that avoids cellular stress due to overexpression of therapeutic proteins
开发用于基因治疗的脂肪细胞,避免因治疗蛋白过度表达而造成的细胞应激
- 批准号:
23H03065 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (B)
Functional analysis of bitter taste receptors in adipocytes and hepatocytes
脂肪细胞和肝细胞中苦味受体的功能分析
- 批准号:
23K05107 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Elucidation of mechanisms for conversion of adipocytes to cancer-associated fibroblasts in osteosarcoma microenvironment
阐明骨肉瘤微环境中脂肪细胞转化为癌症相关成纤维细胞的机制
- 批准号:
23K19518 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Research Activity Start-up
Study on UCP-1 independent metabolic regulation by brown adipocytes
棕色脂肪细胞对UCP-1独立代谢调节的研究
- 批准号:
23K18303 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
NKA/CD36 signaling in adipocytes promotes oxidative stress and drives chronic inflammation in atherosclerosis
脂肪细胞中的 NKA/CD36 信号传导促进氧化应激并驱动动脉粥样硬化的慢性炎症
- 批准号:
10655793 - 财政年份:2023
- 资助金额:
-- - 项目类别:
The mechanisms of the signal transduction from brown adipocytes to afferent neurons and its significance.
棕色脂肪细胞向传入神经元的信号转导机制及其意义。
- 批准号:
23K05594 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Characterizing breast cancer invasion and proliferation when co-aggregated with adipocytes in multicellular spheroids created with a custom bioreactor to augment cell-cell connectivity.
当与多细胞球体中的脂肪细胞共聚集时,表征乳腺癌的侵袭和增殖,该多细胞球体是用定制生物反应器创建的,以增强细胞间的连接。
- 批准号:
10334113 - 财政年份:2022
- 资助金额:
-- - 项目类别:














{{item.name}}会员




