Dissociation Between Hormonal Counterregulatory Responses and Cerebral Glucose Metabolism During Hypoglycemia
John J Lee1, Nadia Khoury2, Angela M Shackleford3
1Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO.
Abstract:
Hypoglycemia is the most common complication of diabetes, causing morbidity and death. Recurrent hypoglycemia alters the cascade of physiological and behavioral responses that maintain euglycemia. The extent to which these responses are normally triggered by decreased whole-brain cerebral glucose metabolism (CMRglc) has not been resolved by previous studies. We measured plasma counterregulatory hormonal responses and whole-brain CMRglc (along with blood-to-brain glucose transport rates and brain glucose concentrations) with 1-[11C]-d-glucose positron emission tomography during hyperinsulinemic glucose clamps at nominal plasma glucose concentrations of 90, 75, 60, and 45 mg/dL (5.0, 4.2, 3.3, and 2.5 mmol/L) in 18 healthy young adults. Clear evidence of hypoglycemic physiological counterregulation was first demonstrated between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L) with increases in both plasma epinephrine (P = 0.01) and glucagon (P = 0.01). In contrast, there was no statistically significant change in CMRglc (P = 1.0) between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L), whereas CMRglc significantly decreased (P = 0.02) between 60 mg/dL (3.3 mmol/L) and 45 mg/dL (2.5 mmol/L). Therefore, the increased epinephrine and glucagon secretion with declining plasma glucose concentrations is not in response to a decrease in whole-brain CMRglc.
Insights
Hypoglycemia triggers counterregulatory hormone release before affecting whole-brain glucose metabolism. This study shows epinephrine and glucagon increase before cerebral glucose metabolism significantly drops in healthy adults.
Area of Science:
- Endocrinology
- Neuroscience
- Metabolism
Background:
- Hypoglycemia is a major diabetes complication, impacting physiological and behavioral responses.
- The role of decreased whole-brain cerebral glucose metabolism (CMRglc) in triggering these responses is unclear.
Purpose of the Study:
- To investigate the relationship between plasma glucose levels, counterregulatory hormonal responses, and whole-brain CMRglc in healthy adults.
- To determine if reduced CMRglc precedes or follows counterregulatory hormonal release during hypoglycemia.
Main Methods:
- Utilized 1-[11C]-d-glucose positron emission tomography to measure whole-brain CMRglc.
- Employed hyperinsulinemic glucose clamps to achieve specific plasma glucose concentrations (90, 75, 60, 45 mg/dL).
- Monitored plasma counterregulatory hormonal responses, including epinephrine and glucagon.
Main Results:
- Counterregulatory hormonal responses (epinephrine, glucagon) were significantly elevated between 75 and 60 mg/dL plasma glucose.
- No significant change in whole-brain CMRglc was observed between 75 and 60 mg/dL.
- CMRglc significantly decreased only between 60 and 45 mg/dL plasma glucose.
Conclusions:
- Increased epinephrine and glucagon secretion during mild hypoglycemia is not driven by a decrease in whole-brain glucose metabolism.
- Counterregulatory hormonal responses precede significant reductions in cerebral glucose utilization in healthy individuals.
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