Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia
Open accessAbstract
AIMS/HYPOTHESIS: Attenuated counterregulation after recurrent hypoglycaemia is a major complication of diabetes treatment. As there is previous evidence for the relevance of sleep in metabolic control, we assessed the acute contribution of sleep to the counterregulatory adaptation to recurrent hypoglycaemia. METHODS: Within a balanced crossover design, 15 healthy, normal-weight male participants aged 18-35 years underwent three hyperinsulinaemic-hypoglycaemic clamps with a glucose nadir of 2.5 mmol/l, under two experimental conditions, sleep and sleep deprivation. Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8 h sleep vs sleep deprivation. The counterregulatory response of relevant hormones (glucagon, growth hormone [GH], ACTH, cortisol, adrenaline [epinephrine] and noradrenaline [norepinephrine]) was measured, and autonomic and neuroglycopenic symptoms were assessed. RESULTS: Sleep deprivation compared with sleep dampened the adaptation to recurrent hypoglycaemia for adrenaline (p=0.004), and this pattern also emerged in an overall analysis including adrenaline, GH and glucagon (p=0.064). After regular sleep, the counterregulatory responses of adrenaline (p=0.005), GH (p=0.029) and glucagon (p=0.009) were attenuated during the 3rd clamp compared with the 1st clamp, but were preserved after sleep deprivation (all p>0.225). Neuroglycopenic and autonomic symptoms during the 3rd clamp compared with the 1st clamp were likewise reduced after sleep (p=0.005 and p=0.019, respectively). In sleep deprivation, neuroglycopenic symptoms increased (p=0.014) and autonomic symptoms were unchanged (p=0.859). CONCLUSIONS/INTERPRETATION: The counterregulatory adaptation to recurrent hypoglycaemia is compromised by sleep deprivation between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neurometabolic memory, and may be a potential target of interventions to treat hypoglycaemia unawareness syndrome.
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Sleep plays a critical role in hypoglycemia counterregulation.
“Emerging evidence suggests that sleep plays a critical role in hypoglycemia counterregulation [ 19 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
After recent antecedent hypoglycemia, epinephrine levels are significantly reduced.
“After recent antecedent hypoglycemia, epinephrine levels are significantly reduced ( Figure 2 ) [ 19 , 30 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
Recent antecedent hypoglycemic episodes cause a defective counterregulation by reducing epinephrine levels.
“The concept of hypoglycemia unawareness also includes that recent antecedent hypoglycemic episodes cause a defective counterregulation by reducing epinephrine levels.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
Recurrent hypoglycemic episodes disrupt the normal release of counterregulatory hormones, such as glucagon, growth hormone (GH), and epinephrine.
“Hypoglycemia unawareness syndrome is commonly observed in individuals with recurrent hypoglycemic episodes disrupting the normal release of counterregulatory hormones, such as glucagon, growth hormone (GH), and epinephrine.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
A vicious cycle of recurrent hypoglycemia with the potential for serious complications can occur.
“Consequently, a vicious cycle of recurrent hypoglycemia with the potential for serious complications can occur [ 18 , 19 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
Neuroglycopenic symptoms during hypoglycemia were preserved upon sleep deprivation.
“Furthermore, neuroglycopenic symptoms during hypoglycemia were preserved upon sleep deprivation [ 19 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
Sleep represents a potential modulator of metabolic memory.
“Furthermore, it is known that sleep represents a potential modulator of metabolic memory.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
Sleep deprivation compared with sleep attenuated the adaptation to recurrent hypoglycemia.
“In a recent study, sleep deprivation compared with sleep attenuated the adaptation to recurrent hypoglycemia.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
The counterregulatory response of the key hormones epinephrine, GH, and glucagon was dampened after recurrent hypoglycemia when participants slept regularly compared to sleep deprivation.
“The counterregulatory response of the key hormones epinephrine, GH, and glucagon was dampened after recurrent hypoglycemia when participants slept regularly compared to sleep deprivation.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
In the same study, counterregulatory response was attenuated after regular sleep.
“In contrast, counterregulatory response was attenuated after regular sleep, which can be considered as a learning process of memory consolidation that implicates the formation of neurometabolic memory and contributes to the development of a hypoglycemia unawareness syndrome [ 19 , 40 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
In a study with two hypoglycemic episodes followed by a third hypoglycemic clamp after one night of regular sleep or sleep deprivation, the hormonal counterregulatory response to hypoglycemia was preserved after sleep loss.
“In a study with two hypoglycemic episodes, followed by a third hypoglycemic clamp after one night of regular sleep or sleep deprivation, the hormonal counterregulatory response to hypoglycemia was preserved after sleep loss.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [19]
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Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications
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- Authors
- Meyhöfer, S., Dembinski, K., Schultes, B., Born, J., Wilms, B., Lehnert, H., Hallschmid, M., & Meyhöfer, S. M.
- Affiliations
- German Center for Diabetes Research (DE)
- University of Lübeck (DE)
- University of Salzburg (AT)
- Corresponding author
- Meyhöfer, Svenja
- Meyhöfer, Sebastian M.
- Venue
- Diabetologia
- Published
- 2022-04-21
- Volume
- 65
- Issue
- 7
- Pages
- 1212-1221
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC9174142
- OpenAlex
- W4224240130
- Cited by
- 7
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Diabetologia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
- Site cant be reached (submittedVersion, cc-by)
- Funders
- DFG (TR-SFB654-B1)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- sleep deprivation, recurrent hypoglycemia, epinephrine, glucagon, growth hormone, ACTH, cortisol, norepinephrine, neuroglycopenic symptoms, autonomic symptoms, sleep and metabolism
- MeSH terms
- Adolescent, Adult, Blood Glucose, Diabetes Mellitus, Type 1, Epinephrine, Glucagon, Humans, Hydrocortisone, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Norepinephrine, Sleep Deprivation, Growth Hormone, Cross-Over Studies, Young Adult
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