Obesity, Insulin Resistance and Brain in Adolescence

中年人的2型糖尿病(T2 DM)一直与以下方面的缺陷有关 近期记忆力、注意力、执行功能和认知效率。胰岛素抵抗(IR)是一种进行性的 糖尿病前期的状况。我们有强有力的初步证据表明，类似的认知问题也存在。 在患有胰岛素抵抗的肥胖青少年中，与匹配的非胰岛素抵抗组相比。该计划的目的是 建议的研究是严格确定肥胖者存在的认知障碍的性质 患有胰岛素抵抗的青少年，并通过系统和标准化的神经心理学和核磁共振-方法 进一步描述这些异常的大脑底物。此外，我们建议确定是否， 相对于匹配的苗条青少年，没有胰岛素抵抗的肥胖青少年有可检测到的认知能力 减损。肥胖和胰岛素抵抗与炎症有关。因此，我们还将评估炎症是否 调节胰岛素抵抗(和/或肥胖)和青春期大脑功能障碍之间的一些联系。 我们寻求资金以减轻飓风桑迪的影响，并促进成功完成 我们建议的具体目标是： 具体目标I：确定肥胖青少年是否存在胰岛素抵抗 与匹配的肥胖、非胰岛素抵抗和瘦青少年相关的记忆和其他认知领域。 特定目的II：确定肥胖青少年是否有胰岛素抵抗的基于MRI的海马区 体积减少、灰质减少和白质异常。 具体目标III：确定肥胖青少年中的炎症标志物是否介导了 胰岛素抵抗与认知能力、海马体体积下降之间的假设联系 减少，灰质减少，以及白质完整性减少。 资金将用于： -关闭、损失评估、重建实验室所花费时间的人员工资， 开设额外的科目以完成目标 -提供完成目标所需的费用； -对完成目标所需的储存样本进行额外化验 我们估计我们需要6个月的时间来弥补因桑迪而损失的时间。

Type 2 diabetes mellitus (T2DM) in middle-aged individuals has been consistently associated with deficits in recent memory, attention, executive function, and cognitive efficiency. Insulin resistance (IR) is a progressive pre-diabetic condition. We have strong preliminary evidence that similar cognitive problems are also present among obese adolescents with IR relative to matched non-insulin resistant groups. The purpose of the proposed study is to rigorously establish the nature of the cognitive impairments present among obese adolescents with IR and by means of a systematic and standardized neuropsychological and MRI-approach to further characterize the brain substrates for those abnormalities. In addition, we propose to ascertain whether, relative to matched lean adolescents, obese adolescents without insulin resistance have detectable cognitive impairments. Obesity and IR are associated with inflammation. Thus, we will also assess whether inflammation mediates some of the associations between IR (and/or obesity) and brain dysfunction in adolescence. We seek funds to mitigate the effects of Hurricane Sandy and facilitate the successful completion of the Specific Aims of our proposal, which are: Specific Aim I: To determine whether obese adolescents with insulin resistance have lower performance on memory and other cognitive domains relative to matched obese non-insulin resistant and lean adolescents. Specific Aim II: To determine whether obese adolescents with insulin resistance have MRI-based hippocampal volume reductions, gray matter reductions, and white matter abnormalities. Specific Aim III: To determine whether among obese adolescents markers of inflammation mediate the hypothesized links between insulin resistance and reductions in cognitive performance, hippocampal volume reductions, reductions in gray matter, and reductions in white matter integrity. Funds will be used for: - Salary of personnel for time spent either in lockout, damage assessment, re-establishing the laboratory, running additional subjects to complete the aims - Supplies costs that are needed to complete the aims; - Extra assays on stored samples needed to complete the aims We estimate that we will need 6 months to make up for the time lost due to Sandy.