Brain Activation During Working Memory Is Altered in Patients With Type 1 Diabetes During Hypoglycemia

  1. Donald C. Simonson7,8
  1. 1Brain Imaging Center, McLean Hospital, Belmont, Massachusetts
  2. 2Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  3. 3Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
  4. 4Research Division, Joslin Diabetes Center, Boston, Massachusetts
  5. 5Research Institute, Winthrop-University Hospital, Mineola, New York
  6. 6Department of Psychiatry, University of Utah, Salt Lake City, Utah
  7. 7Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts
  8. 8Department of Medicine, Harvard Medical School, Boston, Massachusetts
  1. Corresponding author: Nicolas R. Bolo, nbolo{at}


OBJECTIVE To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS Using blood oxygen level–dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses.

RESULTS During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA1c was associated with lower activation in the right parahippocampal gyrus and amygdala (R2 = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups.

CONCLUSIONS BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes.

  • Received April 14, 2011.
  • Accepted August 25, 2011.

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  1. Diabetes vol. 60 no. 12 3256-3264
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