Abstract
Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain’s handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.
Highlights
The brain is one of the most metabolically active organs in the body and it consumes energy disproportionate to its size
Recurrent hypoglycemia forms the basis of hypoglycemia-associated autonomic failure’ (HAAF) and the clinical syndrome of impaired awareness of hypoglycemia by attenuating physiological defenses against subsequent hypoglycemia, increasing the risk for severe hypoglycemia
The progress in metabolic and functional neuroimaging techniques has revealed that recurrent hypoglycemia causes cerebral adaptations to occur on many different levels
Summary
The brain is one of the most metabolically active organs in the body and it consumes energy disproportionate to its size. An improved sensitivity of the 13C-MRS method [142] in combination with an optimized 13C-glucose infusion protocol enabled us to study glucose metabolism in the human brain during hypoglycemia at lower enrichment values [143] With this optimized technique, no differences were observed in cerebral glucose metabolism between hypoglycemia and euglycemia, neither in healthy controls [94], nor in patients with type 1 diabetes [144]. The relative contribution of acetate to brain metabolism in rats exposed to recurrent antecedent hypoglycemia was increased during next-day hypoglycemia, indicating that brain substrate preferences may change rapidly from glucose to alternative substrates if needed [156] To delineate whether this effect was a function of diabetes, prior hypoglycemia or both, the investigators repeated their 13C-acetate study in patients with type 1 diabetes with normal or impaired awareness of hypoglycemia and in healthy controls. Recurrent hypoglycemia enhanced, rather than decreased, thalamic perfusion during subsequent hypoglycemia in healthy controls [170], so that the role of this brain region in the adaptation to hypoglycemia remains uncertain
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