Obesity, Insulin Resistance and Brain in Adolescence

青春期肥胖、胰岛素抵抗和大脑

• 批准号: 8610295
• 负责人: ANTONIO CONVIT
• 金额: $ 52.77万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8610295
• 关键词: 21 year old; Address; Adolescence; Adolescent; Adult; Affect; Age; Appearance; Area; Attention; Base of the Brain; Brain; Brain Injuries; Cerebrum; Child; Childhood; Cognition; Cognitive; Complex; Data; Data Set; Education; Endocrine; Ensure; Ethnic Origin; Evaluation; Female; Foundations; Functional disorder; Future; Gender; Goals; Heterogeneity; Hippocampus (Brain); Hispanics; Impaired cognition; Individual; Inflammation; Insulin; Insulin Resistance; Literature; Magnetic Resonance Imaging; Measurable; Measures; Mediating; Memory; Metabolic; Metabolic Diseases; Methods; Nature; Neuropsychological Tests; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Overweight; Participant; Performance; Procedures; Publications; Race; Relative (related person); Resistance; Socioeconomic Status; Study Subject; Testing; Time; Tissues; United States; Work; case control; cost; design; diabetic; ethnic minority population; executive function; experience; fasting glucose; frontal lobe; gray matter; inflammatory marker; middle age; neuropsychological; neurotrophic factor; public health relevance; response; white matter

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.

描述（由申请人提供）：中年人的 2 型糖尿病 (T2DM) 一直与近期记忆力、注意力、执行功能和认知效率缺陷相关。胰岛素抵抗（IR）是一种进行性糖尿病前期病症。我们有强有力的初步证据表明，与匹配的非胰岛素抵抗群体相比，患有 IR 的肥胖青少年也存在类似的认知问题。拟议研究的目的是严格确定患有 IR 的肥胖青少年中存在的认知障碍的性质，并通过系统化和标准化的神经心理学和 MRI 方法来进一步表征这些异常的大脑基质。此外，我们建议确定，相对于匹配的瘦青少年，没有胰岛素抵抗的肥胖青少年是否存在可检测到的认知障碍。肥胖和IR与炎症有关。因此，我们还将评估炎症是否介导 IR（和/或肥胖）与青春期脑功能障碍之间的某些关联。我们试图在三组青少年中批判性地检验以下假设：在胰岛素抵抗中，IR 测量值与认知以及大脑结构和功能完整性测量值之间存在横断面关联。我们认为，相对于匹配的（肥胖除外）瘦青少年，患有 IR 的肥胖青少年将比没有 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，将其分为三个同等大小的组（空腹血糖水平正常的肥胖胰岛素抵抗个体、空腹血糖水平正常但没有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进行匹配，此外，所有三个组将在年龄、教育、民族（种族）、社会经济地位和性别方面进行 1:1 匹配。我们将确保所有参与者都具备英语能力。所有评估都将使用标准化且可靠的方法。拟议的工作将提供记录大脑参与与儿童肥胖相关的代谢紊乱的关键数据，这将作为未来工作的基础。