236-OR: Sleep Deprivation Prevents Counterregulatory Adaptation to Recurrent Hypoglycaemia

Aims/Hypothesis: Attenuated counterregulation after recurrent hypoglycaemia is a major complication of diabetes treatment. Considering 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 cross-over 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 (SD) . Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8-hour sleep vs. SD. The counterregulatory response of relevant hormones (glucagon, growth hormone (GH) , adrenocorticotropic hormone (ACTH) , cortisol, epinephrine, and norepinephrine) . Moreover, autonomic and neuroglycopenic symptoms were assessed.

Results: SD compared to sleep dampened the adaptation to recurrent hypoglycaemia of epinephrine (p=0.004) , and this pattern also emerged in an overall analysis including epinephrine, GH, and glucagon (p=0.064) . Whereas after regular sleep, counterregulatory responses of epinephrine (p=0.005) , GH (p=0.029) , and glucagon (p=0.009) were attenuated during the third compared to the first clamp, they were preserved after SD (all p>0.225) . Neuroglycopenic and autonomic symptoms during the third compared to the first clamp were likewise reduced after sleep (p=0.0 and p=0.019, respectively) . In SD, neuroglycopenic symptoms increased (p=0.014) and autonomic symptoms remained unchanged (p=0.859) .

Conclusions/Interpretation: The counterregulatory adaptation to recurrent hypoglycaemia is compromised by SD between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neuro-metabolic memory and a potential target of interventions to improve hypoglycaemia unawareness.