Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes

识别 1 型糖尿病低血糖无意识的脑基质

基本信息

  • 批准号:
    8687019
  • 负责人:
  • 金额:
    $ 24.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-08-05 至 2014-09-06
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Patients with type 1 diabetes (T1DM) are exposed to the risk of experiencing severe episodes of hypoglycemia (HG) as they undergo insulin treatment to maintain the glucose control that is necessary to prevent diabetes complications. Recurrent HG can lead to development of the hypoglycemia-associated autonomic failure (HAAF) and to the syndrome of HG unawareness, where patients lose the ability to recognize symptoms of HG until they become unable to treat themselves. Strict avoidance of HG partially restores awareness of HG, however it is very difficult to achieve. Drugs and therapies that directly target the brain mechanisms responsible for HG unawareness have promise as better ways to prevent and/or reverse HAAF, thus crucially advancing care for patients with diabetes. In order to effectively design and monitor such treatments, it is necessary however to first characterize the physiological and pathological brain responses to HG, a research topic that has been only partly covered by current literature and that is at the center of the current proposal. I this project we will utilize state-of-the-art MRI methods to monitor non-invasively the brain responses during controlled experimental HG in a subject population which includes HG-unaware and HG-aware T1DM subjects, and healthy controls with and without a treatment that induces HAAF. Hypoglycemia-induced brain activations will be identified during different phases of HG by changes in cerebral blood flow. Multiple brain functionally-connected networks will also be monitored by using functional MRI based on the blood oxygenation level contrast, with a novel imaging protocol recently developed within the Human Connectome Project. Our central hypothesis is that altered brain responses to HG in HG-unaware T1DM subjects, as indentified by measures of brain activation patterns and functionally- connected brain networks, are a result of antecedent HG episodes, not diabetes. Therefore we expect that the activation patterns and the brain networks of HG-unaware T1DM subjects will be different from healthy and HG-aware T1DM subjects, but will resemble those of healthy controls who undergo HAAF induction. Our research team is uniquely positioned to conduct this research, as it has gained extensive expertise in mastering high magnetic field MR applications, and holds a long track record of MR research in diabetes. Ultimately, the study design of this proposal will allow identifying with unprecedented sensitivity the altered brain responses to HG in those T1DM patients who are unable to recognize the symptoms of HG, thus filling a critical gap of knowledge which will have significant impact in defining strategies that will reduce the complications of management of diabetes. Since our study has been designed to be conducted on a clinical 3 Tesla scanner, the measurements that we utilize here to detect the brain responses to HG can be easily extended to future clinical trials aiming to monitor the efficacy of new treatments targeting the brain substrates of HG.
描述(申请人提供):1型糖尿病(T1 DM)患者在接受胰岛素治疗以维持预防糖尿病并发症所必需的血糖控制时,面临经历严重低血糖(HG)发作的风险。反复发生的HG可导致低血糖相关的自主神经衰竭(HAF)和HG意识丧失的综合征,即患者失去识别HG症状的能力,直到他们变得无法治疗自己。严格避免HG在一定程度上恢复了人们对HG的认识,但实现起来非常困难。直接针对导致HG意识不清的大脑机制的药物和疗法有望成为预防和/或逆转HAAF的更好方法,从而至关重要地促进对糖尿病患者的护理。然而,为了有效地设计和监测这种治疗方法,有必要首先表征大脑对HG的生理和病理反应,这是一个目前文献只涵盖了部分内容的研究课题,也是当前提议的核心。在这个项目中,我们将利用最先进的MRI方法,在受试者群体中非侵入性地监测受试者在受控实验性HG期间的大脑反应,受试者包括未意识到HG和意识到HG的T1 DM受试者,以及接受和不接受HAAF治疗的健康对照组。低血糖诱导的脑激活将通过脑血流的变化来确定在HG的不同阶段。多个大脑功能连接的网络也将通过使用基于血氧水平对比的功能磁共振进行监测,这是最近在人类连接组项目中开发的一种新的成像协议。我们的中心假设是,通过测量大脑激活模式和功能连接的大脑网络,不知道HG的T1 DM受试者对HG的大脑反应改变是先前HG发作的结果,而不是糖尿病。因此,我们预计,未意识到HG的T1 DM受试者的激活模式和脑网络将不同于健康和有HG意识的T1 DM受试者,但将类似于接受HAF诱导的健康对照组。我们的研究团队在进行这项研究方面处于独特的地位,因为它在掌握高磁场磁共振应用方面获得了广泛的专业知识,并在糖尿病的磁共振研究方面拥有长期的记录。最终,这项建议的研究设计将允许以前所未有的敏感性确定那些无法识别HG症状的T1 DM患者对HG的大脑反应的变化,从而填补知识的关键空白,这将对制定减少糖尿病治疗并发症的策略产生重大影响。由于我们的研究是在临床3特斯拉扫描仪上进行的,我们在这里用来检测大脑对HG的反应的测量方法可以很容易地扩展到未来的临床试验,目的是监测针对HG大脑底物的新治疗的有效性。

项目成果

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Silvia Mangia其他文献

Silvia Mangia的其他文献

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{{ truncateString('Silvia Mangia', 18)}}的其他基金

Linking Connectomics to Biochemical Trajectories of Aging: How the Human Brain Ages Differentially in Key Regions of the Default Mode Network
将连接组学与衰老的生化轨迹联系起来:人脑默认模式网络关键区域的衰老方式如何差异
  • 批准号:
    9447437
  • 财政年份:
    2017
  • 资助金额:
    $ 24.82万
  • 项目类别:
Linking Connectomics to Biochemical Trajectories of Aging: How the Human Brain Ages Differentially in Key Regions of the Default Mode Network
将连接组学与衰老的生化轨迹联系起来:人脑默认模式网络关键区域的衰老方式如何差异
  • 批准号:
    9926788
  • 财政年份:
    2017
  • 资助金额:
    $ 24.82万
  • 项目类别:
Linking Connectomics to Biochemical Trajectories of Aging: How the Human BrainAges Differentially in Key Regions of the Default Mode Network
将连接组学与衰老的生化轨迹联系起来:人脑在默认模式网络的关键区域中如何差异化衰老
  • 批准号:
    10552469
  • 财政年份:
    2017
  • 资助金额:
    $ 24.82万
  • 项目类别:
Linking Connectomics to Biochemical Trajectories of Aging: How the Human Brain Ages Differentially in Key Regions of the Default Mode Network
将连接组学与衰老的生化轨迹联系起来:人脑默认模式网络关键区域的衰老方式如何差异
  • 批准号:
    10159810
  • 财政年份:
    2017
  • 资助金额:
    $ 24.82万
  • 项目类别:
Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes
识别 1 型糖尿病低血糖无意识的脑基质
  • 批准号:
    9269187
  • 财政年份:
    2014
  • 资助金额:
    $ 24.82万
  • 项目类别:
Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes
识别 1 型糖尿病低血糖无意识的脑基质
  • 批准号:
    8759737
  • 财政年份:
    2014
  • 资助金额:
    $ 24.82万
  • 项目类别:
Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes
识别 1 型糖尿病低血糖无意识的脑基质
  • 批准号:
    8923080
  • 财政年份:
    2014
  • 资助金额:
    $ 24.82万
  • 项目类别:
Functional MRS at 7T to Study Neuronal Inhibition in Humans
7T 功能性 MRS 研究人类神经元抑制
  • 批准号:
    8792259
  • 财政年份:
    2014
  • 资助金额:
    $ 24.82万
  • 项目类别:
Functional MRS at 7T to Study Neuronal Inhibition in Humans
7T 功能性 MRS 研究人类神经元抑制
  • 批准号:
    8699876
  • 财政年份:
    2014
  • 资助金额:
    $ 24.82万
  • 项目类别:
THE IN VIVO NEURON-TO-ASTROCYTE LACTATE SHUTTLE IN HUMAN BRAIN
人脑中的体内神经元到星形胶质细胞的乳酸穿梭
  • 批准号:
    8362881
  • 财政年份:
    2011
  • 资助金额:
    $ 24.82万
  • 项目类别:

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