The long term objective of this project is to determine the effect of diabetes and the hypoglycemic consequences of intensive therapy on in vivo brain metabolism and function in humans. The investigators' experiments are designed to address the hypothesis that the human brain adapts to chronic hyperglycemia and recurrent hypoglycemia so as to ensure sufficient substrate delivery to meet its energy needs. To test this hypothesis the investigators will first examine the effect of poorly controlled diabetes on the maintenance of intracerebral glucose concentrations and on the kinetics of cerebral glucose transport and metabolism. Subsequent experiments will determine whether recurrent hypoglycemia alters these variables in subjects with type I diabetes. These studies will be performed under strictly controlled metabolic conditions using high field (4 Tesla) 1H magnetic resonance spectroscopy. Additional experiments will use high field functional magnetic resonance imaging to determine whether poorly controlled diabetes alters the activation of the occipital cortex by a visual stimulus.
The specific aims of this project are:
Aim 1, to determine whether glucose concentrations in the occipital cortex and the periventricular white matter in diabetic subjects with antecedent hyperglycemia are comparable to concentrations measured in normal controls.
Aim 2, to determine whether the kinetics of glucose transport across the blood brain barrier in both gray and white matter are the same or different in diabetic subjects with antecedent hyperglycemia as compared to healthy controls.
Aim 3, to determine whether intracerebral glucose concentrations in the occipital cortex and the periventricular white matter in diabetic subjects with recurrent hypoglycemia are comparable to intracerebral concentrations measured in normal controls.
Aim 4, to determine whether the kinetics of glucose transport across the blood brain barrier in both gray and white matter are the same or different in diabetic subjects with recurrent hypoglycemia as compared to healthy controls.
Aim 5, to determine whether the functional activation of the occipital cortex is the same in diabetic patients as it is in control. At the completion of the studies the investigators will have defined the effects of chronic hyperglycemia and recurrent hypoglycemia on brain glucose metabolism in humans and examined functional activation of the visual cortex in diabetic subjects. Such knowledge will allow us to better judge the risks and benefits of intensive glycemic control and to more effectively assist patients in the selection of appropriate goals for long term diabetes management.
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