This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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