THE EFFECT OF HYPOGLYCEMIA ON BRAIN FUNCTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 低血糖是限制1型糖尿病患者（T1 DM）最佳护理的关键因素。复发性低血糖可导致低血糖无意识（HU）。然而，很少有人知道的神经通路的变化，葡萄糖感知，皮层活动，认知与HU。拟议的研究将使用功能磁共振成像检查大脑激活，认知能力，反调节激素分泌，并在三个精心挑选的对照组（N=60）的症状识别。无HU的T1 DM患者、伴有HU的T1 DM患者和非糖尿病志愿者，以确定无意识患者中存在的逆调节缺陷是否由于异常下丘脑反应而发生。我们将进一步探讨其他脑区是否在低血糖反应中被激活，以及与无意识的患者相比，有意识的T1 DM患者和对照受试者的这些脑区是否不同。 我们还将研究支持认知的皮层激活。这项研究计划将使我们能够确定参与葡萄糖感知的大脑区域以及最容易发生低血糖的皮质区域。由于治疗目标是维持血糖水平接近正常，T1 DM患者发生轻度复发性低血糖的风险升高。我们需要更好地了解这种现象的长期后遗症，以设计临床护理方法，帮助患者实现更严格的血糖控制。此外，更好地了解低血糖相关认知障碍的神经基础可以为如何预测、避免和适应可能由意外低血糖事件引起的特定认知限制提供重要指导。 我们研究的主要目的是确定低血糖无意识患者是否比有意识的糖尿病患者和对照受试者激活葡萄糖感知区域（下丘脑）的强度更低，血糖更低，以及他们在低血糖期间对认知挑战的反应是否不同。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypoglycemia is a critical factor limiting optimal care in Type 1 diabetes patient (T1DM). Recurrent hypoglycemia can led to hypoglycemia unawareness (HU). However, little is know about the neural pathways underlying the changes in glucose sensing, cortical activity, and cognition associate with HU. The proposed studies will use fMRI to examine brain activation, cognitive performance, counter regulatory hormone secretion, and symptom recognition in three carefully selected contrast groups (N=60). T1DM patients without HU, T1DM patients with HU and non-diabetic volunteers to determine whether the counter regulatory defect present in unaware patients occurs due to an abnormal hypothalamic response. We will further explore whether other brain regions are activated in response to hypoglycemia and whether these regions differ in aware T1DM patients and control subjects as compared with the unaware patients. We will also investigate cortical activation in areas that support cognition. This research program will allow us to identify the brain regions involved in glucose sensing as well as cortical regions most susceptible to hypoglycemia. Due to the therapeutic goal of maintaining blood glucose levels as near normal, there is an elevated risk for mild recurrent hypoglycemia in T1DM. We need to better understand the long-term sequelae of this phenomenon to design approaches to clinical care to help patients achieve tighter glycemic control. Further a better understanding of the neural underpinnings of hypoglycemia associated cognitive impairments could provide important guidance on how to anticipate, avoid, and adapt to specific cognitive limitation that may be caused by an unanticipated hypoglycemic event. A major aim of our study is to determine whether patients with hypoglycemia unawareness activate the glucose sensing region (hypothalamus) less strongly and a t a lower blood glucose than aware diabetic patients and control subjects and whether they respond differently to cognitive challenges during hypoglycemia.