title: Brain activation during working memory is altered in patients with type 1 diabetes during hypoglycemia.
abstract: OBJECTIVE
  To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes.
  
  
  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 HbA(1c) was associated with lower activation in the right parahippocampal gyrus and amygdala (R(2) = 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.
authors: Brain Imaging Center, McLean Hospital, Belmont, Massachusetts, USA. nbolo@bidmc.harvard.edu
authors: Nicolas R
authors: NR
authors: Bolo
authors: Gail
authors: G
authors: Musen
authors: Alan M
authors: AM
authors: Jacobson
authors: Katie
authors: K
authors: Weinger
authors: Richard L
authors: RL
authors: McCartney
authors: Veronica
authors: V
authors: Flores
authors: Perry F
authors: PF
authors: Renshaw
authors: Donald C
authors: DC
authors: Simonson
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose