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Adaptation in brain glucose uptake following recurrent hypoglycemia
P J Boyle1, R J Nagy, A M O'Connor
1Department of Medicine, University of New Mexico, Albuquerque 87131.
Summary
Recurrent hypoglycemia in humans allows the brain to maintain normal glucose uptake and cognitive function. Adaptations prevent symptoms and counterregulatory hormone release until very low glucose levels are reached.
Area of Science:
- Endocrinology
- Neuroscience
- Metabolism
Background:
- Hypoglycemia impairs brain glucose metabolism.
- Adaptations to sustained hypoglycemia are known in animal models but not in humans.
- Human data on brain glucose uptake (BGU) during recurrent hypoglycemia is lacking.
Purpose of the Study:
- To test the hypothesis that adaptations occur to maintain normal BGU during recurrent hypoglycemia in humans.
- To investigate the effects of recurrent hypoglycemia on cognitive function and counterregulatory hormone responses.
Main Methods:
- Twelve healthy humans underwent a stepped glucose clamp protocol over 4 days.
- Brain glucose uptake, cerebral blood flow, and cognitive function were measured.
- Recurrent hypoglycemia was induced, followed by a period of controlled glucose levels.
Main Results:
- Initially, BGU was impaired at 3.61 mmol/liter, and symptoms occurred at this level.
- After 56 hours of recurrent hypoglycemia, BGU was maintained at all glucose levels.
- Cognitive function was preserved until lower glucose concentrations, and symptoms were delayed to 2.50 mmol/liter on the final day.
Conclusions:
- Adaptations occur in humans that maintain normal BGU and cerebral function during recurrent hypoglycemia.
- Counterregulatory hormone responses and hypoglycemic symptoms are forestalled until extremely low glucose concentrations.
- These findings suggest a protective mechanism against recurrent hypoglycemia in humans.