Reversibility of brain glucose kinetics in type 2 diabetic subjects

2 型糖尿病受试者脑葡萄糖动力学的可逆性

• 批准号: 10664102
• 负责人: Elizabeth Sanchez Rangel
• 金额: $ 19.62万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664102
• 关键词: 3-Dimensional; Acute; Age; Animals; Area; Blood - brain barrier anatomy; Brain; Brain region; Central Nervous System; Cerebrum; Chronic; Citric Acid Cycle; Closure by clamp; Consumption; Data; Deuterium; Diabetes Mellitus; Down-Regulation; Energy Metabolism; Energy-Generating Resources; Exposure to; Feasibility Studies; Funding; Future; Glucose; Glucose Clamp; Glucose Transporter; Glutamates; Glutamine; Glycosylated hemoglobin A; Goals; Human; Hyperglycemia; Image; Impaired cognition; Individual; Intervention; Intravenous infusion procedures; Kinetics; Label; Light; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Mentors; Metabolic; Methodological Studies; Methodology; Methods; Morbidity - disease rate; NMR Spectroscopy; Nerve Degeneration; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Occipital lobe; Participant; Patients; Peripheral; Physiological; Pilot Projects; Plasma; Play; Prefrontal Cortex; Prevalence; Protons; Reporting; SLC2A1 gene; Sample Size; Techniques; Testing; Training; Type 2 diabetic; blood glucose regulation; brain dysfunction; cell injury; cognitive change; design; diabetes mellitus therapy; experience; glucose metabolism; glucose transport; glycemic control; gray matter; healthy weight; improved; magnetic resonance spectroscopic imaging; metabolic abnormality assessment; metabolic imaging; mortality; non-diabetic; novel; post intervention; prevent; response

Project summary/abstract The prevalence of type 2 diabetes mellitus continues to rise worldwide and despite different treatment options, many patients fail to achieve glycemic target, which leads to increased morbidity and mortality. Chronic exposure to hyperglycemia has been shown in both animal and human studies to decrease glucose transport into the brain, presumably through down-regulation of GLUT1 at the blood brain barrier, which has been postulated to be a protective adaptation of the central nervous system against the harmful consequences of hyperglycemia. However, GLUT1 down regulation may lead to reduced brain glucose metabolism leading to neuronal damage, neurodegeneration and cognitive decline. Whether these changes in cerebral glucose transport seen in patients with poorly controlled diabetes can be reversed is unknown. The main goal of this study is to determine whether improvement of glucose control in poorly controlled T2DM patient will restore brain glucose transport kinetics and rigorously assess which factors (i.e. duration DM and glycemic control) contribute to the observed improvements by using classic metabolic studies as well as state-of-the-art brain nuclear magnetic resonance spectroscopy (MRS) techniques. The findings obtained from this study will help elucidate if intensive diabetes therapy may be associated with reduced brain dysfunction from hyperglycemia.

项目概要/摘要 尽管治疗方法不同，2 型糖尿病的患病率在全球范围内持续上升 许多患者未能达到血糖目标，从而导致发病率和死亡率增加。 动物和人类研究均表明，长期暴露于高血糖会降低血糖 转运到大脑，可能是通过血脑屏障处 GLUT1 的下调， 被认为是中枢神经系统针对有害后果的保护性适应 高血糖症。然而，GLUT1 下调可能导致脑葡萄糖代谢降低，从而导致 神经元损伤、神经变性和认知能力下降。脑葡萄糖的这些变化是否 在糖尿病控制不佳的患者中观察到的转运是否可以逆转尚不清楚。此次活动的主要目标 研究旨在确定控制不佳的 T2DM 患者血糖控制的改善是否会恢复 脑葡萄糖转运动力学并严格评估哪些因素（即糖尿病持续时间和血糖控制） 通过使用经典的代谢研究以及最先进的大脑来促进观察到的改善 核磁共振波谱（MRS）技术。这项研究的结果将有助于 阐明强化糖尿病治疗是否可能与减少高血糖引起的脑功能障碍有关。