Brain glucose concentrations in healthy humans subjected to recurrent hypoglycemia

Amy B. Criego, Ivan Tkac, Anjali Kumar, William Thomas, Rolf Gruetter, Elizabeth R Seaquist

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 1H-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 μmol/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.

Original languageEnglish (US)
Pages (from-to)525-530
Number of pages6
JournalJournal of Neuroscience Research
Issue number4
StatePublished - Nov 15 2005


  • Glucose
  • Hypoglycemia
  • Recurrent hypoglycemia


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