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Adaptation in brain glucose uptake following recurrent hypoglycemia.
Open accessAbstract
Brain glucose metabolism is impaired during hypoglycemia, but, if sustained, brain metabolism reverts to normal in animal models--data in man are lacking. We tested the hypothesis that adaptations occur to allow maintenance of normal rates of brain glucose uptake (BGU) following recurrent hypoglycemia in man. Twelve normal humans were studied over 4 days. On the initial day, arterial plasma glucose concentrations were decreased from 4.72 to 2.50 mmol/liter in five 0.56 mmol/liter steps. Cerebral blood flow, brain arteriovenous glucose difference, BGU, and cognitive function were quantitated at each step. BGU was initially impaired at the 3.61 mmol/liter glucose step (P = 0.04) and was antedated by increments in epinephrine that began at 4.16 mmol/liter (P = 0.03). The onset of hypoglycemic symptoms occurred during the 3.61 mmol/liter glucose step (P = 0.02), whereas tests of cognitive function generally deteriorated at the 3.05 mmol/liter step (P < 0.05). During the next 56 hr, mean glucose concentrations were kept at 2.9 +/- 0.1 mmol/liter and reached normal only during meals. The stepped clamp protocol was repeated beginning at 4.16 mmol/liter on the last day. No decrement in BGU was observed at any step; cognitive function was preserved until significantly lower glucose concentrations on the final day relative to the first (P = 0.04). Subjects remained asymptomatic of hypoglycemia until they reached a glucose concentration of 2.50 mmol/liter (P < 0.001 vs. day 1), while initial increments in all counterregulatory hormones were forestalled to lower glucose steps than on day 1. Therefore, adaptations occur that allow normal BGU and cerebral function to be maintained during recurrent systemic hypoglycemia. Counterregulatory events that should result in symptoms of hypoglycemia and increments in endogenous glucose production are prevented until extremely subnormal glucose concentrations.
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“During the second half of the night, glucose consumption increases due to increased REM sleep requiring more energy.46,47”
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“Brain glucose metabolism, as measured by PET, decreases by 30–40%.46,47”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [46]
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“almost immediate reductions in cognitive performance occur when blood glucose concentrations fall below 3.4 mmol·L -1 46-55”
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Verhulst, C. E. M., Fabricius, T. W., Teerenstra, S., Kristensen, P. L., Tack, C. J., McCrimmon, R. J., Heller, S., Evans, M. L., Amiel, S. A., Pedersen-Bjergaard, U., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05749-8 · Cited by 34
Diabetes mellitus and the central nervous system
McCall, A. L. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)51012-6 · Cited by 33
Protective Effect of Insulin against Hypoglycemia-Associated Counterregulatory Failure
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Shift of glycaemic thresholds for cognitive function in hypoglycaemia unawareness in humans
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Metadata
- Authors
- Boyle, P. J., Nagy, R. J., O'Connor, A. M., Kempers, S. F., Yeo, R. A., & Qualls, C.
- Affiliations
- University of New Mexico (US)
- ORCID
- Qualls, C
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-09-27
- Volume
- 91
- Issue
- 20
- Pages
- 9352-9356
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44810
- OpenAlex
- W2093219766
- Cited by
- 208
- References
- 45
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 12 · 2012: 13
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ns029972-05)
- National Institute of Neurological Disorders and Stroke (1 R29 NS29972-01A1)
- National Center for Research Resources (5 M01 RR00997-17, M01RR000997)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Clinical Neurology › Neurological and metabolic disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- recurrent hypoglycemia, brain glucose uptake, brain glucose metabolism, epinephrine, cognitive function, cerebral blood flow, arteriovenous glucose difference, hypoglycemic symptoms, endogenous glucose production
- MeSH terms
- Acclimatization, Adult, Blood Glucose, Brain, Cognition, Epinephrine, Female, Glucagon, Glucose, Humans, Hydrocortisone, Hypoglycemia, Insulin, Male, Memory, Norepinephrine, Pancreatic Polypeptide, Reference Values, Regional Blood Flow, Growth Hormone, Glucose Clamp Technique
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