The JDRF Center for the Study of Hypoglycemia at YaleUnder the direction of Dr. Sherwin, this center brings together 16 clinical investigators in such areas as insulin delivery systems, clinical physiology, glucose sensor technology, behavioral research and imaging technology. There are two major components to Center activities, namely a clinical trial involving children with diabetes and a basic science component that utilizes novel technologies to study brain function and metabolism and how they are affected by hypoglycemia. The clinical trial, led by Dr. Tamborlane tests whether the introduction of glucose sensor technology can be used in the clinical setting to reduce the risk of severe hypoglycemia in children receiving intensive insulin therapy. These studies led the NIH to initiate Direct Net, which has provided critical information on the utility and the limitations of glucose sensor technology. The long-term goal of the project is to develop a closed loop artificial pancreas, which would be an enormous benefit for patients with diabetes. The basic science component tests from multiple perspectives (microdialysis, MR Spectroscopy, and fMRI) the hypothesis that a key role of brain glucose metabolism is to provide the energy needed to maintain glutamate-glutamine cycling and neurotransmission and that hypoglycemia prevents these processes, and this in turn diminishes regional brain activation in response to a cognitive task. On the other hand, diabetic patients with a history frequent hypoglycemia and reduced recognition of hypoglycemia have developed metabolic brain adaptations which allow them more effectively use alternative fuels for the brain's basic energy needs, in particular short and medium chain fatty acids. The long-term goals of the Center are to develop a mechanical (artificial) pancreas to prevent hypoglycemia, to discover drugs that could reverse defects in hypoglycemia defense systems in diabetes, or to identify alternative fuels that could be effectively used by the brain to protect it from injury. All the participants are DERC members.