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. Graphical abstract

Objective To investigate the impact of metabolic status on choroidal thickness in healthy subjects, patients with obesity, and type 2 diabetes. Design and Methods Fasting blood glucose, insulin, IGF-1, and choroidal thickness measured by optical coherence tomography were assessed in healthy normal-weight (n=17), obese participants (n=20), and in obese participants with T2D (n=16). Results Choroidal thickness was increased in obese participants and obese participants with T2D as compared to healthy normal-weight participants (P<0.0001). There was a negative correlation between IGF1 and choroidal thickness (r=-0.268, P=0.050) for all cohorts. Furthermore, BMI (R2=0.209; P=0.002; beta=0.388) and HOMA-IR (R2=0.074; P=0.015; beta=0.305) are independent variables of ChT, explaining 20.9% and 7.4% of its variance (both p<0.016), whereas age, sex, and IGF-1 were not significant confounders of ChT (p>0.975). Conclusion Choroidal thickness is associated with metabolic characteristics, i.e. BMI and HOMA-IR. Due to the key role of choroidal function in retinal physiology, future studies are needed to evaluate whether metabolic traits, choroidal thickness, and potential metabolic eye complications are mechanistically linked.