title: Brain glucose concentrations in patients with type 1 diabetes and hypoglycemia unawareness.
abstract: Although it is well established that recurrent hypoglycemia leads to hypoglycemia unawareness, the mechanisms responsible for this are unknown. One hypothesis is that recurrent hypoglycemia alters brain glucose transport or metabolism. We measured steady-state brain glucose concentrations during a glucose clamp to determine whether subjects with type 1 diabetes and hypoglycemia unawareness may have altered cerebral glucose transport or metabolism after exposure to recurrent hypoglycemia. We compared 14 subjects with diabetes and hypoglycemia unawareness to 27 healthy control subjects. Brain glucose concentrations were measured under similar metabolic conditions using in vivo (1)H nuclear magnetic resonance (NMR) spectroscopy at 4 Tesla during a hyperglycemic clamp (plasma glucose = 16.7 mmol/l) with somatostatin and insulin. Subjects with type 1 diabetes and hypoglycemia unawareness had significantly higher brain glucose concentrations compared to that in controls under the same conditions (5.5 +/- 0.3 vs. 4.7 +/- 0.1 micromol/g wet weight, P = 0.016). These data suggest that changes in brain glucose transport or metabolism may occur as a result of recurrent hypoglycemia.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN 55455, USA. crieg002@umn.edu
authors.forename: Amy B
authors.initials: AB
authors.lastname: Criego
authors.forename: Ivan
authors.initials: I
authors.lastname: Tkac
authors.forename: Anjali
authors.initials: A
authors.lastname: Kumar
authors.forename: William
authors.initials: W
authors.lastname: Thomas
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Seaquist
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D012008:Recurrence; D014316:Tritium / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D014316:Tritium; D005934:Glucagon; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine