Obesity, Insulin Resistance and Brain in Adolescence

描述（由申请人提供）：中年人的2型糖尿病（T2 DM）一直与近期记忆、注意力、执行功能和认知效率的缺陷相关。胰岛素抵抗（IR）是一种进行性糖尿病前期疾病。我们有强有力的初步证据表明，类似的认知问题也存在于肥胖青少年IR相对于匹配的非胰岛素抵抗组。拟议研究的目的是严格确定肥胖青少年IR中存在的认知障碍的性质，并通过系统和标准化的神经心理学和MRI方法进一步表征这些异常的大脑基质。此外，我们建议确定是否，相对于匹配的瘦青少年，肥胖青少年没有胰岛素抵抗有可检测的认知障碍。肥胖和IR与炎症相关。因此，我们还将评估炎症是否介导IR（和/或肥胖）和青春期脑功能障碍之间的某些关联。我们试图批判性地研究，在三组青少年中，胰岛素抵抗的假设，有横截面之间的关联措施的IR和认知和结构和功能的大脑完整性的措施。我们认为，肥胖青少年IR将有更大的减少比肥胖青少年没有IR相对于匹配（除了肥胖）瘦青少年。在这项研究中，我们将研究180名16-21岁的个体，分为三个相等的组（空腹血糖水平正常的肥胖胰岛素抵抗个体，空腹血糖水平正常且无明显胰岛素抵抗证据的肥胖青少年，空腹血糖水平正常且胰岛素功能正常的瘦青少年）。两个肥胖组将在肥胖方面匹配，此外，所有三个组将在年龄、教育、种族（人种）、社会经济地位和性别方面1：1匹配。我们将确保所有参与者的英语能力。所有评价都将使用标准化和可靠的方法。拟议的工作将提供关键数据，记录大脑参与与儿童肥胖相关的代谢紊乱，这将作为未来工作的基础。

DESCRIPTION (provided by applicant): 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 to critically examine, in three groups of adolescents, the hypotheses that in insulin resistance there are cross-sectional associations between measures of IR and measures of cognition and structural and functional brain integrity. We propose that obese adolescents with IR will have larger reductions than obese adolescents without IR relative to matched (other than on obesity) lean adolescents. In this effort we will study 180 individuals 16-21 years of age separated into three equal sized groups (obese insulin resistant individuals with normal fasting glucose levels, obese adolescents with normal fasting glucose levels and no evidence of significant insulin resistance, and lean adolescents with normal fasting glucose levels and normal insulin function). The two obese groups will be matched on obesity and, in addition, all three groups will be matched 1:1 on, age, education, ethnicity (race), socio-economic status, and gender. We will ensure that all participants are competent in English. All evaluations will use standardized and reliable methods. The proposed work will provide key data documenting brain involvement in metabolic disorders associated with obesity in childhood, which will serve as the foundation for future work.