Diet and Exercise Trial to Improve Insulin Resistance, Increase Cerebral Blood Flow, Alter Metabolomic Biomarkers, and Decrease Alzheimer's Disease Risk

项目摘要 代谢综合征(METS)与糖尿病和心血管疾病的发展有关 疾病；然而，它也与认知衰退和痴呆症有关。我们已经证明了大都会是 与脑血流量降低和记忆功能有关的中老年晚期增高症 罹患阿尔茨海默病(AD)的风险。胰岛素抵抗(IR)是METS的核心，也是一个标志 IR的特点是空腹血糖(FBG)较高，餐后高血糖。 虽然我们和其他人已经证明了IR和CBF之间的联系，以及从 从观察的角度来看，还没有研究调查干预后的CBF和认知 运动和碳水化合物限制饮食(CRD)，旨在改善或正常化IR和血糖 动态平衡。我们建议确定改善或正常化血糖稳态对脑血流的影响。 和认知，通过饮食和运动，在IR和AD发展风险的个人。 虽然运动和CRD已被证明可以改善IR和血糖控制，但我们只有有限的 了解这些改进背后的机制。营养代谢组学--全球衡量标准 和代谢谱的解释，评估饮食与内源基因-蛋白质的相互作用 卡斯卡德和肠道微生物群。此外，运动已被证明对人类有影响 代谢体。最后，许多代谢物与IR和空腹血糖受损有特定的联系 (IFG)。我们建议使用代谢组学来测量当个体正常化或 改善胰岛素抵抗和血糖稳态。 这项探索性研究是否应该揭示脑血流量增加和记忆力改善对 饮食和运动，那么对这些高危个体的早期治疗可能会为疾病提供新的途径--病程 修改。及早有效地进行风险因素管理的策略可能有助于减少 新陈代谢和认知能力下降的风险。此外，这项研究是否应该揭示新陈代谢的变化 与糖尿病早期症状相一致的异常，代谢组学可能是一种有效的方法 在我们的精准护理目标中补充疾病风险分析。

Project Summary Metabolic syndrome (MetS) is associated with the development of diabetes and cardiovascular disease; however it is also linked with cognitive decline and dementia. We have shown that MetS is associated with lower cerebral blood flow (CBF) and memory function in late middle-aged adults at increased risk for developing Alzheimer’s disease (AD). Insulin resistance (IR) is at the core of MetS, and a hallmark feature of IR is higher fasting blood glucose (FBG) as well as post prandial hyperglycemia. While we and others have demonstrated links between IR and CBF as well as cognition from an observational perspective, no studies have investigated CBF and cognition after an intervention involving exercise and a carbohydrate restricted diet (CRD) designed to improve or normalize IR and glucose homeostasis. We propose to determine the effect of improving or normalizing glucose homeostasis on CBF and cognition, through diet and exercise, in individuals with IR and at risk for the development of AD. While exercise and a CRD have been shown to improve IR and glycemic control, we have only limited knowledge of the mechanisms behind these improvements. Nutritional metabolomics, the global measurement and interpretation of metabolic profiles, assesses the interaction of diet with the endogenous gene-protein cascade and the gut microbiome. Additionally, exercise has been shown to have an impact on the human metabolome. Finally, numerous metabolites have been specifically linked to IR and impaired fasting glucose (IFG). We propose to use metabolomics to measure changes in metabolites as individuals normalize or improve IR and glucose homeostasis. Should this exploratory study reveal increased brain blood flow and improved memory in response to diet and exercise, then early treatment of these individuals at risk might offer new avenues for disease-course modification. Strategies towards early and effective risk factor management could be of value in reducing the risk of metabolic as well as cognitive decline. In addition, should this study reveal changes in metabolic abnormalities consistent with early indications of diabetes, metabolomics could be an effective approach to complement disease risk analysis in our goal toward precision care.