Understanding pancreatic endocrine and exocrine loss in pre-type 1 diabetes

了解 1 型糖尿病前期的胰腺内分泌和外分泌丧失

基本信息

  • 批准号:
    10461979
  • 负责人:
  • 金额:
    $ 64.11万
  • 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:
    2020-08-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

For decades, type 1 diabetes (T1D) has been considered a disorder resulting from chronic autoimmune destruction of insulin-producing pancreatic β-cells. While a broad number of intellectual advances have improved our understanding of the natural history of T1D, significant gaps remain in the complex series of physiological events, both immunologic and metabolic, that initiate β-cell autoimmunity, spur the loss of functional β-cell mass, and culminate in clinical diabetes. People with a first-degree relative (FDR) with T1D have ~15-fold increased lifetime risk of T1D. Importantly, natural history studies have informed the use of islet-associated autoantibodies (AAb) as biomarkers to track progression to overt disease, and these biomarkers were transformative for the field. Nevertheless, there remains significant heterogeneity in T1D progression, and additional biomarkers of T1D risk are urgently needed. Studies by this group demonstrated that pancreas weights from organ donors with T1D were significantly reduced, including at diabetes onset, and provided essential data using the ratio of pancreas weight to body weight or BMI (relative pancreas volume, RPV) to normalize for subjects’ sex and age. Yet more profound in terms of T1D pathogenesis, reductions in pancreas size were also observed in single AAb+ donors compared to autoantibody-negative (AAb-) control donors. Subsequently, a pilot cross-sectional DP3 trial in NIH-NIDDK TrialNet (TN) subjects was completed using magnetic resonance imaging (MRI) to quantify RPV in FDR in comparison to controls and patients with recent-onset T1D (< 1-year duration). Strikingly, a reduction in RPV was observed in FDR without AAb (AAb-) with further reductions in RPV for FDR with single and multiple AAb+. We hypothesize that a smaller pancreas size is predictive of T1D risk and a decline in pancreas size over time is predictive for diabetes progression. This hypothesis will be tested at four TrialNet centers in FDR subjects. To test our hypothesis, we will: Aim 1: Quantify pancreas volume (PV) and morphology in FDR subjects by AAb status and test for longitudinal changes in PV. Aim 2: Correlate PV and morphology with surrogate markers of β-cell function and mass. Aim 3: Correlate PV and morphology with surrogate markers of acinar function. Aim 4: Perform SNP analyses for genetic determinants of pancreas size. The successful completion of these studies will serve to expand the prognostic utility of pancreas MRI in understanding T1D pathophysiology. Non-contrast pancreas MRI is safe and readily performed in children and could add to biomarkers informing T1D risk predication, and potentially, progression. Endocrine-exocrine interactions are novel and are expected to provide a new understanding of diabetes pathogenesis. Earlier identification of subjects at highest risk for T1D progression is expected to significantly impact prevention strategies and their successful application before the loss of functional β-cell mass is irreversible.
几十年来,1型糖尿病(T1D)一直被认为是一种由慢性自身免疫引起的疾病

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Type 1 Diabetes: A Disorder of the Exocrine and Endocrine Pancreas.
1 型糖尿病:胰腺外分泌和内分泌疾病。
  • DOI:
    10.33696/immunology.5.177
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Bruggeman,BrittanyS;Schatz,DesmondA
  • 通讯作者:
    Schatz,DesmondA
Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Type 1 Diabetes in Acute Pancreatitis Consortium.
  • DOI:
    10.1097/mpa.0000000000002077
  • 发表时间:
    2022-07-01
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Wasserfall, Clive;Dyer, Anne-Marie;Speake, Cate;Andersen, Dana K.;Baab, Kendall Thomas;Bellin, Melena D.;Broach, James R.;Campbell-Thompson, Martha;Chinchilli, Vernon M.;Lee, Peter J.;Park, Walter G.;Pratley, Richard E.;Saloman, Jami L.;Sims, Emily K.;Tang, Gong;Yadav, Dhiraj;Yazici, Cemal;Conwell, Darwin L.
  • 通讯作者:
    Conwell, Darwin L.
Substance Use Affects Type 1 Diabetes Pancreas Pathology: Implications for Future Studies.
  • DOI:
    10.3389/fendo.2021.778912
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Bruggeman BS;Campbell-Thompson M;Filipp SL;Gurka MJ;Atkinson MA;Schatz DA;Jacobsen LM
  • 通讯作者:
    Jacobsen LM
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MARTHA CAMPBELL-THOMPSON其他文献

MARTHA CAMPBELL-THOMPSON的其他文献

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{{ truncateString('MARTHA CAMPBELL-THOMPSON', 18)}}的其他基金

Multi-omic 3D tissue maps for a Human BioMolecular Atlas
人类生物分子图谱的多组学 3D 组织图谱
  • 批准号:
    10685583
  • 财政年份:
    2020
  • 资助金额:
    $ 64.11万
  • 项目类别:
Understanding pancreatic endocrine and exocrine loss in pre-type 1 diabetes
了解 1 型糖尿病前期的胰腺内分泌和外分泌丧失
  • 批准号:
    10226911
  • 财政年份:
    2020
  • 资助金额:
    $ 64.11万
  • 项目类别:
Pathways and critical regulators of early beta-cell dysfunction in type 1 diabetes
1 型糖尿病早期 β 细胞功能障碍的途径和关键调节因子
  • 批准号:
    10202585
  • 财政年份:
    2019
  • 资助金额:
    $ 64.11万
  • 项目类别:
Pathways and critical regulators of early beta-cell dysfunction in type 1 diabetes
1 型糖尿病早期 β 细胞功能障碍的途径和关键调节因子
  • 批准号:
    10441263
  • 财政年份:
    2019
  • 资助金额:
    $ 64.11万
  • 项目类别:
Pathways and critical regulators of early beta-cell dysfunction in type 1 diabetes
1 型糖尿病早期 β 细胞功能障碍的途径和关键调节因子
  • 批准号:
    9802936
  • 财政年份:
    2019
  • 资助金额:
    $ 64.11万
  • 项目类别:
Neuromodulation-based treatment of diabetes: identifying anatomical and physiological pancreatic innervation targets
基于神经调节的糖尿病治疗:确定解剖学和生理学胰腺神经支配目标
  • 批准号:
    9752693
  • 财政年份:
    2016
  • 资助金额:
    $ 64.11万
  • 项目类别:
Defining Islet Heterogeneity Using Single Islet Transcriptomics
使用单胰岛转录组学定义胰岛异质性
  • 批准号:
    8812982
  • 财政年份:
    2014
  • 资助金额:
    $ 64.11万
  • 项目类别:
Pancreas Volume in Preclinical Type 1 Diabetes
临床前 1 型糖尿病的胰腺体积
  • 批准号:
    8644494
  • 财政年份:
    2013
  • 资助金额:
    $ 64.11万
  • 项目类别:
Leica Laser Microdissection Microscope for a Shared Resource
共享资源的徕卡激光显微切割显微镜
  • 批准号:
    8448032
  • 财政年份:
    2013
  • 资助金额:
    $ 64.11万
  • 项目类别:
Pathology/Immunology Core
病理学/免疫学核心
  • 批准号:
    8319521
  • 财政年份:
    2011
  • 资助金额:
    $ 64.11万
  • 项目类别:

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