Skeletal Health in Type 1 Diabetes and the Role of Diabetic Kidney Disease
1 型糖尿病的骨骼健康和糖尿病肾病的作用
基本信息
- 批准号:10459481
- 负责人:
- 金额:$ 66.62万
- 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:2020-09-10 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAgeAgingAlbuminuriaAllopurinolAncillary StudyArchivesBiological MarkersBiopsyBone DensityBone DiseasesChronic Kidney FailureCohort StudiesComplementComplicationComplications of Diabetes MellitusDataDiabetes MellitusDiabetic AngiopathiesDiabetic NephropathyDual-Energy X-Ray AbsorptiometryEnrollmentEpidemiologyFractureFunctional disorderGeometryGlomerular Filtration RateGlucoseGlycosylated hemoglobin AGoldHealthHip FracturesHormonesHyperglycemiaImageImpairmentIndividualInsulin-Dependent Diabetes MellitusInterventionIohexolKidneyKidney DiseasesLabelLongevityMeasurementMeasuresMetabolismMicrovascular DysfunctionMineralsMorbidity - disease ratePTH geneParticipantPatient CarePatternPeripheralPersonsPlacebosPlayPopulationPreventionRandomizedRecording of previous eventsRenal functionResearchResolutionRiskRisk FactorsRoleSerumSeveritiesShapesSkeletonSpecimenTetracyclinesTimeUric AcidVisitVitamin DVitamin D-Binding ProteinWomanX-Ray Computed Tomographybonebone fragilitybone geometrybone imagingbone massbone qualitybone strengthbone turnoverclinical carediabeticepidemiologic dataevidence based guidelinesfracture riskglucose monitorglycemic controlmenmortalitynegative affectpost interventionpreventprotein metabolitescreeningscreening guidelinesskeletal
项目摘要
PROJECT SUMMARY/ABSTRACT
Type 1 diabetes (T1D) is associated with increased risk of fracture throughout the lifespan. As
individuals with T1D now live to older ages, when morbidity and mortality from fracture are greatest, it is crucial
to understand this skeletal fragility and identify strategies to mitigate fracture risk. Bone mineral density is
reduced, but fracture is elevated out of proportion to this reduction, indicating that other factors—“bone
quality”—also contribute to the skeletal fragility. These may include low bone turnover and compromised bone
geometry and microstructure. The presence of a diabetes microvascular complication is associated with
particular skeletal fragility, but studies to date have been unable to disentangle specific contributions of each
complication, nor to determine whether associations are independent of glycemic control. Of the microvascular
complications, diabetic kidney disease may be especially detrimental, as other skeletal effects of T1D may be
compounded by bone and mineral derangements of chronic kidney disease, including abnormal bone turnover
and vitamin D metabolism. Our central hypothesis is that diabetic kidney disease particularly affects the
already vulnerable T1D skeleton and plays a key role in the pathophysiology of diabetic skeletal fragility.
The PERL trial presents a unique opportunity to understand the overlapping impact of these effects, as
it has extensively characterized the kidney function of adult participants with T1D and diabetic kidney disease
of varied severity. This 3-year trial of the effects of allopurinol vs. placebo on kidney function has ended, and
participants are enrolled in an observational post-trial cohort study. In the 148 participants at 7 PERL centers,
we propose an ancillary study that will add skeletal imaging for bone density (with dual-energy X-ray
absorptiometry) and bone microstructure and estimated strength (with high-resolution peripheral quantitative
computed tomography). We will also add analyses on stored serum specimens from 3 time points during
PERL. A subset of participants (N=25) will undergo tetracycline-labeled bone biopsy. We will estimate
relationships of gold-standard iohexol GFR and albuminuria—measured longitudinally—with skeletal
parameters (Aim 1a). Then, we will determine if those relationships vary across a wider spectrum of kidney
function, by combining data from PERL with consistently-acquired skeletal imaging data from 220 adults in the
EDIC study, many of whom have normal GFR and no albuminuria (Aim 1b). We will next determine if glycemic
control is independently associated with skeletal parameters in PERL (Aim 2). Finally, we will examine whether
high or low parathyroid hormone and bone turnover marker levels are associated with skeletal parameters, and
whether altered vitamin D metabolites partially explain the kidney-bone relationship (Aim 3). In the biopsy
subset, we will explore whether PTH and bone turnover markers correlate with histomorphometric turnover.
This research has the potential to shape the care of patients with T1D by informing screening approaches and
interventions. Ultimately, it could help reduce fracture risk in our aging T1D population.
项目摘要/摘要
1型糖尿病(T1D)与整个生命周期中骨折的风险增加有关。作为
T1D的个体现在生活到年龄较大,当骨折的发病率和死亡率最大时,这是至关重要的
了解这种骨骼脆弱性并确定减轻断裂风险的策略。骨矿物密度为
减少,但骨折与这种减少成比例不合时间,表明其他因素 - “骨头
质量” - 也有助于骨骼脆弱性。这些可能包括低骨转换和骨骼损害
几何和微观结构。糖尿病微血管并发症的存在与
特定的骨骼脆弱性,但迄今为止的研究无法解除每个的特定贡献
并发症,也不确定关联是否独立于血糖控制。微血管
并发症,糖尿病性肾脏疾病可能特别有害,因为T1D的其他骨骼影响可能是
由慢性肾脏疾病的骨骼和矿物变化复合,包括异常骨转换
和维生素D代谢。我们的中心假设是糖尿病肾脏疾病特别影响
已经脆弱的T1D骨骼,在糖尿病骨骼脆弱性的病理生理中起关键作用。
PERL试验为了解这些影响的重叠影响提供了一个独特的机会,因为
它已经广泛地表征了成年参与者T1D和糖尿病肾脏疾病的肾功能
严重程度不同。这项为期三年的阿嘌呤醇与安慰剂对肾脏功能的影响的试验已经结束,并且
参与者参与了一项观察性审判后队列研究。在7个Perl中心的148名参与者中,
我们提出了一项辅助研究,该研究将增加骨密度的骨骼成像(带双能量X射线
绝对微观结构和估计强度(具有高分辨率外围定量
计算机断层扫描)。我们还将在3个时间点上对存储的血清样品进行分析
珀尔。参与者的一部分(n = 25)将接受四环素标记的骨活检。我们将估计
金色标准的iohexol GFR和蛋白尿的关系 - 纵向进行骨骼的关系
参数(AIM 1A)。然后,我们将确定这些关系在更广泛的肾脏中是否有所不同
功能,将来自PERL的数据与来自220名成年人的始终获得的骨骼成像数据相结合
EDIC研究,其中许多人具有正常的GFR,没有蛋白尿(AIM 1B)。接下来,我们将确定是否血糖
控制与Perl中的骨骼参数独立相关(AIM 2)。最后,我们将研究是否
高或低甲状旁腺激素和骨转换标记水平与骨骼参数有关,并且
维生素D代谢物的改变是否部分解释了肾骨关系(AIM 3)。在活检中
子集,我们将探索PTH和骨转换标记是否与组织形态计量计的相关。
这项研究有可能通过告知筛查方法和
干预措施。最终,它可以帮助降低我们老龄化T1D人群的骨折风险。
项目成果
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{{ truncateString('ANN V SCHWARTZ', 18)}}的其他基金
Skeletal Health in Type 1 Diabetes and the Role of Diabetic Kidney Disease
1 型糖尿病的骨骼健康和糖尿病肾病的作用
- 批准号:
10684140 - 财政年份:2020
- 资助金额:
$ 66.62万 - 项目类别:
Skeletal Health in Type 1 Diabetes and the Role of Diabetic Kidney Disease
1 型糖尿病的骨骼健康和糖尿病肾病的作用
- 批准号:
10032520 - 财政年份:2020
- 资助金额:
$ 66.62万 - 项目类别:
Skeletal Health in Type 1 Diabetes and the Role of Diabetic Kidney Disease
1 型糖尿病的骨骼健康和糖尿病肾病的作用
- 批准号:
10256021 - 财政年份:2020
- 资助金额:
$ 66.62万 - 项目类别:
ASBMR Symposium: The Effects of Diabetes and Disordered Energy Metabolism on Skel
ASBMR 研讨会:糖尿病和能量代谢紊乱对骨骼的影响
- 批准号:
8785584 - 财政年份:2014
- 资助金额:
$ 66.62万 - 项目类别:
Undercarboxylated osteocalcin, body fat, and diabetes in older adults
老年人中羧基化骨钙素、体脂肪和糖尿病
- 批准号:
7738539 - 财政年份:2009
- 资助金额:
$ 66.62万 - 项目类别:
Undercarboxylated osteocalcin, body fat, and diabetes in older adults
老年人中羧基化骨钙素、体脂肪和糖尿病
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7896451 - 财政年份:2009
- 资助金额:
$ 66.62万 - 项目类别:
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