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Regional Brain Activation during Hypoglycemia in Type 1 Diabetes

Research Division (G.M., A.D., K.W., A.M.J.), Joslin Diabetes Center, Boston, Massachusetts 02215; Departments of Psychiatry (G.M., N.R.B., K.W., P.F.R., A.M.J.) and Medicine (D.C.S., A.R.), Harvard Medical School, Boston, Massachusetts 02115; Division of Endocrinology, Diabetes, and Hypertension (D.C.S., A.R.), Brigham and Women’s Hospital, Boston, Massachusetts 02115; Brain Imaging Center (N.R.B., P.F.R.), McLean Hospital, Belmont, Massachusetts 02478; and Department of Diagnostic Imaging (J.T.), St. Joseph’s Health Care, London, Ontario, Canada N6A 4V2

Address all correspondence and requests for reprints to: Gail Musen, Ph.D., Joslin Diabetes Center, 1 Joslin Place Room 350, Boston, Massachusetts 02215. E-mail: gail.musen{at}joslin.harvard.edu.

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

Objective: Our objective was to 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: This was a cross-sectional study evaluating brain activity using functional magnetic resonance imaging in conjunction with a hyperinsulinemic hypoglycemic clamp to lower glucose from euglycemia (90 mg/dl) to hypoglycemia (50 mg/dl).

Setting: The study was performed at the Brain Imaging Center in the McLean Hospital.

Study Participants: Seven type 1 diabetic patients between 18 and 50 yr old and six matched control subjects were included in the study.

Intervention: Hyperinsulinemic hypoglycemic clamp was performed.

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

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 < 0.001). Each group also activated unique brain areas not active in the other group.

Conclusions: This application of functional magnetic resonance imaging 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.

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