Obesity, Insulin Resistance and Brain in Adolescence

描述（由申请人提供）：2型糖尿病（T2DM）在中年个体中一直与近期记忆、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，与非胰岛素抵抗组相比，患有IR的肥胖青少年也存在类似的认知问题。本研究的目的是通过系统和标准化的神经心理学和核磁共振成像方法来进一步表征这些异常的大脑基质，严格确定肥胖青少年IR中存在的认知障碍的本质。此外，我们建议确定，相对于匹配的瘦青少年，肥胖青少年没有胰岛素抵抗是否有可检测的认知障碍。肥胖和IR与炎症有关。因此，我们还将评估炎症是否介导了IR（和/或肥胖）与青春期脑功能障碍之间的一些关联。我们试图在三组青少年中批判性地检查胰岛素抵抗的假设，即IR测量与认知、结构和功能脑完整性测量之间存在横断面关联。我们认为，相对于匹配的（除了肥胖）瘦青少年，有IR的肥胖青少年比没有IR的肥胖青少年有更大的减少。在这项工作中，我们将研究180名16-21岁的个体，将其分为三个大小相等的组（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的肥胖青少年，以及空腹血糖水平正常且胰岛素功能正常的瘦青少年）。这两个肥胖组将根据肥胖程度进行匹配，此外，这三个组将根据年龄、教育、民族（种族）、社会经济地位和性别进行1:1的匹配。我们将确保所有参与者都精通英语。所有评估将采用标准化和可靠的方法。这项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，这将为未来的工作奠定基础。

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.