Context: Mechanisms underlying the brain response to hypoglycemia are not well understood.

Objective: Determine the blood glucose level at which the hypothalamus and other brain regions are activated in response to hypoglycemia in type 1 diabetic patients and control subjects.

Design: Cross-sectional study evaluating brain activity using functional magnetic resonance imaging (fMRI) in conjunction with a hyperinsulinemic hypoglycemic clamp to lower glucose from euglycemia (90 mg/dL) to hypoglycemia (50 mg/dL).

Setting: Brain Imaging Center, Mclean Hospital.

Study Participants: Seven type 1 diabetic patients between 18–50 years old and 6 matched control subjects.

Intervention: Hyperinsulinemic hypoglycemic clamp

Main Outcome Measure: Blood glucose level at peak hypothalamic activation, amount of regional brain activity during hypoglycemia in both groups, difference in regional brain activation between groups.

Results: The hypothalamic region activates at 68 ± 9 mg/dL in control subjects and 76 ± 8 mg/dl in diabetic patients during hypoglycemia induction. Brainstem, anterior cingulate cortex, uncus and putamen were activated in both groups (p < .001). Each group also activated unique brain areas not active in the other group.

Conclusions: This application of fMRI can be used to identify the glucose level at which the hypothalamus is triggered in response to hypoglycemia and whether this threshold differs across patient populations. This study suggests that a core network of brain regions is recruited during hypoglycemia in both diabetic patients and control subjects.