HIERARCHICAL BRAIN AND PHYSIOLOGICAL RESPONSES TO HYPOGLYCEMIA AND HAAF IN T1DM

T1DM 患者对低血糖和 HAAF 的分层大脑和生理反应

• 批准号: 8886223
• 负责人: Ana Maria Arbelaez
• 金额: $ 40.65万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-15 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8886223
• 关键词: Acute; Adult; Awareness; Biological Markers; Blood Glucose; Brain; Brain imaging; Brain region; Cause of Death; Cerebrovascular Circulation; Cessation of life; Clinical; Cognition; Complication; Complications of Diabetes Mellitus; Development; Diabetes Mellitus; Epinephrine; Event; Failure; Fire - disasters; Functional Magnetic Resonance Imaging; Glucagon; Glucose; Goals; Hormonal; Hormones; Hypoglycemia; Hypothalamic structure; Impaired cognition; Impairment; Incidence; Individual; Insulin-Dependent Diabetes Mellitus; Intervention; Lead; Life; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mediating; Methods; Modeling; Morbidity - disease rate; Network-based; Neurobehavioral Manifestations; Neurons; Neurotransmitter Receptor; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Patients; Physiological; Play; Prefrontal Cortex; Process; Recruitment Activity; Recurrence; Regional Blood Flow; Rest; Risk; Role; Signal Transduction; Spin Labels; Symptoms; Syndrome; System; Testing; Thalamic structure; Therapeutic; blood glucose regulation; counterregulation; experience; falls; glycemic control; imaging modality; improved; in vivo; innovation; insulin secretion; interdisciplinary approach; neural circuit; neuroimaging; non-diabetic; prevent; prospective; public health relevance; response; therapeutic target; type I diabetic; young adult

 DESCRIPTION (provided by applicant): Hypoglycemia is the limiting factor in the glycemic control of diabetes, causing morbidity and death. Recurrent hypoglycemia causes both defective glucose counterregulation and loss of hypoglycemic symptoms during subsequent hypoglycemia, constituting the clinical syndrome of hypoglycemia-associated autonomic failure (HAAF). The mechanisms underlying the signaling of these responses during hypoglycemia and the loss of these responses during HAAF are thought to involve the brain. To date no effective clinical method has shown to reduce the incidence of hypoglycemia without the risk of compromising glycemic control. Thus, a better understanding of the mechanisms underlying the loss of the hypoglycemic responses may help us identify new and innovative therapeutic targets. We hypothesize that there is hierarchical activation of several hypoglycemia-sensitive brain regions that form a functional network in response to declining blood glucose levels, and a potential loss of the connectivity in this network leads to HAAF in individuals with T1DM. With a multidisciplinary approach we will test this hypothesis, using integrated quantitative brain imaging measurements of regional blood flow (ASL-MRI) and functional connectivity (BOLD rs-fMRI) during hyperinsulinemic euglycemic (~90mg/dL) - stepped hypoglycemic (~65-55-45mg/dL) clamps in 20 type 1 diabetic (T1DM) patients with HAAF, 20 T1DM without HAAF and in 20 healthy young adults in a model of HAAF. By determining the changes in BOLD signal during HAAF in DM, we will identify a neuroimaging biomarker that characterizes the effects of HAAF in vivo in T1DM patients to predict outcomes in planned prospective interventional studies.

 描述（由申请人证明）：低血糖是糖尿病的血糖控制的限制因素，导致疾病和死亡导致葡萄糖反调节有缺陷和降低血糖症状机理THESESTHESE STT的信号传导这些SAF被抗衡，迄今为止，没有有效的临床方法降低了低血糖的发生率，因此受到损害的血糖的风险。可以帮助我们确定新的和创新的治疗方法。使用多学科，我们将使用综合的定量脑成像测量（ASL-MRI）和功能连接（ASL-MRI）BOLD RS RS-FMRI）进行测试 - ）20型1型糖尿病（T1DM）ITH HAAF，无HAAF的20个T1DM，在HAAF模型中的20个健康的年轻人中的20个健康的年轻人。干预研究。