title: Brain glucose concentrations in healthy humans subjected to recurrent hypoglycemia.
abstract: Mechanisms responsible for hypoglycemia unawareness remain unknown. Previously, we found that patients with type 1 diabetes and hypoglycemia unawareness had increased brain glucose concentrations as measured by (1)H-magnetic resonance spectroscopy (MRS) compared with controls measured under the same metabolic condition, suggesting that an alteration in brain glucose transport and/or metabolism may play a role in the pathogenesis of hypoglycemia unawareness. To determine whether the brain glucose concentration is altered in normal subjects subjected to recurrent hypoglycemia, we compared the brain glucose concentrations measured in healthy subjects after three episodes of hypoglycemia to blunt the counterregulatory response over 24 hr and compared this value with that measured at a time remote from the antecedent hypoglycemia protocol. Sixteen subjects (9 M/7 F, age 36 +/- 10 years, mean +/- SD) underwent three hypoglycemic clamps for 30 min at 8 AM (0 hr), 5 PM (9 hr), and 7 AM (24 hr). After the third hypoglycemic clamp, subjects underwent a hyperglycemic clamp during which brain glucose concentration was measured by MRS at 4 T. Brain glucose concentration after repeated hypoglycemia was not different from the brain glucose concentration measured in the same subjects during a control study (5.1 +/- 0.8 vs. 4.5 +/- 0.5 mumol/g wet weight, respectively, P = 0.05). These observations suggest that brain glucose transport or metabolism is not altered following short episodes of recurrent hypoglycemia in healthy human volunteers.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, USA.
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; D001921:Brain / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D007328:Insulin; D005947:Glucose