Obesity, Insulin Resistance and Brain in Adolescence

描述(申请人提供)：中年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有关。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，与匹配的非胰岛素抵抗组相比，患有胰岛素抵抗的肥胖青少年也存在类似的认知问题。这项拟议研究的目的是严格确定患有胰岛素抵抗的肥胖青少年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核磁共振方法来进一步表征这些异常的大脑基础。此外，我们建议确定，相对于匹配的苗条青少年，没有胰岛素抵抗的肥胖青少年是否有可检测到的认知障碍。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在IR(和/或肥胖)和青春期脑功能障碍之间的某些联系中起中介作用。我们试图在三组青少年中批判性地检验假设，即在胰岛素抵抗中，IR测量与认知测量以及结构和功能大脑完整性之间存在横截面关联。我们认为有胰岛素抵抗的肥胖青少年比没有胰岛素抵抗的肥胖青少年相对于匹配的(除肥胖以外的)瘦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，将其分为三组(空腹血糖水平正常的肥胖胰岛素抵抗患者，空腹血糖水平正常但没有明显胰岛素抵抗证据的肥胖青少年，以及空腹血糖水平正常、胰岛素功能正常的瘦削青少年)。这两个肥胖群体将在肥胖方面进行匹配，此外，所有三个群体将在年龄、教育程度、民族(种族)、社会经济地位和性别方面进行1：1的匹配。我们将确保所有参与者都能胜任英语。所有评价都将使用标准化和可靠的方法。这项拟议的工作将提供记录大脑参与儿童肥胖相关代谢障碍的关键数据，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.