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

基本信息

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
项目类别：
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

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

展开

项目摘要

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.

项目摘要/摘要 2型糖尿病的患病率在全球范围内持续上升，尽管治疗不同选择，许多患者无法实现血糖靶标，从而导致发病率和死亡率增加。在动物和人类研究中已经显示出长期暴露于高血糖的人，以减少葡萄糖进入大脑被认为是中枢神经系统抵抗有害后果的保护性适应高血糖。但是，GLUT1降低调节可能导致大脑葡萄糖代谢减少导致神经元损伤，神经退行性和认知能力下降。这些脑葡萄糖的变化是否无法逆转控制糖尿病较差的患者的运输尚不清楚。主要目标研究是为了确定控制不良的T2DM患者中葡萄糖控制是否会恢复脑葡萄糖转运动力学并严格评估哪些因素（即持续时间DM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进核磁共振光谱（MRS）技术。从这项研究中获得的发现将有助于阐明强化糖尿病治疗是否可能与高血糖症的脑功能障碍降低有关。