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Neurocognition in youth with prediabetes

Neurocognition in youth with prediabetes
糖尿病前期青少年的神经认知
批准号:
10224174
负责人:
SONIA CAPRIO
金额:
$66.78万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-15 至 2024-07-31

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中文摘要
翻译
总结 越来越多的证据将人类肥胖和糖尿病与认知功能障碍和痴呆联系起来1-51。而 在人类中的因果关系尚不清楚,可能是双向的,从啮齿动物的研究中可以清楚地看出,饮食诱导 肥胖和相关的代谢功能障碍导致认知受损52 -56。支持这一点的机制 肥胖、饮食和代谢功能障碍的影响和相对贡献仍然未知。特别 对我们回应的资助机会公告的兴趣是阐明葡萄糖与葡萄糖之间的联系, 调节和认知。虽然葡萄糖耐受不良是2型糖尿病(T2 D)的诊断,但最近的一项系统研究表明, 对86篇研究T2 D和认知的论文进行的综述仅发现, 认知68,与其他外周血糖指标相关的证据更少 调节(例如,胰岛素浓度、胰岛素作用、胰岛素抵抗)68.这是一个重大差距, 知识,因为它阻碍了减轻神经认知风险的策略的发展 并发症拟议的研究直接解决了这一知识差距。更具体地说,我们的目标是 通过纵向评估,提供外周葡萄糖耐受不良对神经认知作用的明确测试 参加青年发病糖尿病(PYOD)发病机制研究的青年的认知和脑功能 (R 01 DK 111038)葡萄糖耐受或不耐受,但年龄、性别、BMI和中心 肥胖症PYOD队列提供了研究T2 D认知障碍的绝佳机会,因为 参与者是糖尿病前期,因此不患有与T2 D相关的慢性疾病。我们也 我建议使用一种新的神经影像学范式来评估中枢胰岛素抵抗(IR), 可能解开中枢和外周IR对神经认知的影响46和纹状体的间接标志物, 研究IR、多巴胺与神经认知的关系。更具体地说,我们的 目的是(1)检测外周糖耐量受损(IGT)和/或中枢IR是否影响 独立于肥胖的神经认知功能;(2)测试血糖变化是否 代谢和/或肥胖预测和先于神经认知的变化;和(3)为了测试是否 认知功能障碍和衰退与多巴胺信号有关。我们预计这些结果 将告知策略的发展,以减轻发展神经认知障碍的风险, 识别处于风险中的个体和可能从额外治疗中受益的个体,提供了一种新的 药物干预的治疗靶点,并提供有关认知障碍发生率的关键信息。 下降
英文摘要
SUMMARY Accumulating evidence links human obesity and diabetes with cognitive dysfunction and dementia 1-51. While the causality is unknown in humans, and likely bi-directional, it is clear from work in rodents that diet induced obesity and associated metabolic dysfunction cause impaired cognition52-56. The mechanisms supporting this effect and the relative contribution of adiposity, diet and metabolic dysfunction remain unknown. Of particular interest to the funding opportunity announcement to which we respond is elucidating the link between glucose regulation and cognition. Although glucose intolerance is diagnostic of type 2 diabetes (T2D), a recent systematic review of 86 papers examining T2D and cognition only found a weak association between glycaemia and cognition 68 and there is even less evidence for an association with other measures of peripheral glucose regulation (e.g., insulin concentration, insulin action, insulin resistance)68. This represents a major gap in knowledge because it impedes the development of strategies to mitigate the risk of neurocognitive complications. The proposed research directly addresses this gap in knowledge. More specifically, we aim to provide a definitive test of the role of peripheral glucose intolerance on neurocognition, by longitudinal evaluation of cognitive and brain function in youth enrolled in the Pathogenesis of Youth Onset Diabetes (PYOD) study (R01DK111038) who are either glucose tolerant or intolerant but matched for age, gender, BMI and central adiposity. The PYOD cohort provides an exceptional opportunity to study cognitive impairment in T2D because the participants are pre-diabetic and thus do not suffer from chronic conditions associated with T2D. We also propose to use a new neuroimaging paradigm developed to assess central insulin resistance (IR) so that we may disentangle the effects of central and peripheral IR on neurocognition 46 and an indirect marker of striatal dopamine signaling to investigate the relation between IR, dopamine and neurocognition. More specifically, our aims are to (1) To test whether impaired peripheral glucose tolerance (IGT) and/or central IR influence neurocognitive function independently from adiposity; (2) To test whether change in glucose metabolism and/or adiposity predicts and precedes change in neurocognition; and (3) To test whether cognitive dysfunction and decline is associated with dopamine signaling. We anticipate that these results will inform the development of strategies to mitigate the risk of developing neurocognitive impairment, aid in the identification of individuals who are at-risk and who might benefit from additional therapy, provide a novel therapeutic target for pharmacological intervention and provide critical information about the rate of cognitive decline.
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Neurocognition in youth with prediabetes
  • 批准号:
    10413361
  • 项目类别:
  • 资助金额:
    $20.94万
  • 财政年份:
    2017
  • 负责人:
    SONIA CAPRIO
  • 依托单位:
Neurocognition in youth with prediabetes
  • 批准号:
    9767116
  • 项目类别:
  • 资助金额:
    $76.11万
  • 财政年份:
    2017
  • 负责人:
    SONIA CAPRIO
  • 依托单位:
Pathogenesis of youth onset pre-diabetes and Type 2 diabetes
  • 批准号:
    10688197
  • 项目类别:
  • 资助金额:
    $76.4万
  • 财政年份:
    2016
  • 负责人:
    SONIA CAPRIO
  • 依托单位:
Pathogenesis of youth onset pre-diabetes and Type 2 diabetes
  • 批准号:
    10361972
  • 项目类别:
  • 资助金额:
    $76.85万
  • 财政年份:
    2016
  • 负责人:
    SONIA CAPRIO
  • 依托单位:
海外基金