Selective slow-wave sleep suppression affects glucose tolerance and melatonin secretion A.A. Polishchuk1, K.M. Liaukovich1, М. Meira e Cruz3, K.A. Saltykov1, А.N. Nizhnik2, Y.V. Ukraintseva1 1, Institute of Higher Nervous Activity and Neurophysiology RAS , Moscow, Russian Federation; 2, ArhiMed Clinique for New Medical Technologies, Moscow, Russian Federation; 3, Sleep Unit of Autonomic Function Lab, Cardiovascular Center of University of Lisbon, Portugal Introduction As reported earlier, slow-wave sleep (SWS) suppression impairs morning glucose tolerance [Tasali et al., 2008; Herzog et al., 2013] but exact mechanisms that underlie this effect remain unclear. Among the candidates are the changes in melatonin secretion that are closely related to sleep quality and influence synthesis, secretion and action of insulin [Cipolla-Neto et al., 2014]. The present study aimed to explore a possible role of melatonin in glucose tolerance impairment after SWS suppression. Materials and methods Participants: 16 healthy male volunteers, mean age 23.4 ± 0.6, with regular sleep-wake cycle (bedtimes between 23:00 and 24:00 h and wake-up times between 07:00 and 08:00 h). Procedure: According to a randomized, balanced cross-over design each volunteer participated in two experimental sessions (Figure 1): a session with selective SWS suppression during night sleep and a session with regular night sleep (control). The participants arrived at the research unit at 19:45 h. After first saliva sample was obtained (20:00 h) and until bedtime (23:00) they were kept in dim-light (<10 lux). At 22:40 h, the participants were prepared for nocturnal polysomnography. At 23:00 h, they went to bed, and the lights were turned off. At 07:00 h, the participants were woken up. Salivary samples were collected seven times: three times in the evening; twice at night; and twice in the morning (immediately after awakening and 40 min later). Night samples and first morning one were collected in the dark (0 lx). SWS suppression was achieved by presenting an acoustic tone with gradually rising sound intensity. In the morning an oral glucose tolerance test (OGTT) was performed and blood glucose was measured in finger-prick capillary samples using system FreeStyle Precision Neo (Abbott). Saliva samples were analyzed by liquid chromatography-tandem mass spectrometry for melatonin. Polysomnograms were scored according to standard AASM criteria (Iber et al., 2007). Data Analysis: Paired t-tests for sleep variables and Wilcoxon matched pairs tests for glucose and melatonin concentrations were performed. <10 lx 0 lx Figure 1. Study Design. The schema illustrates the two experimental conditions: one session with slow-wave sleep (SWS) suppression during 8 h of night-time sleep and one session with 8 h of regular night-time sleep (control). Results * ** Table 1. Mean values of polysomnographic data (min) in control sessions and in sessions with SWS suppression. Regular Sleep SWS suppression Р Total sleep time 422,50 (11,61) 402,13 (14,77) 0,135 Sleep period time 463,86 (5,53) 454,54 (6,66) 0,298 WASO 39,39 (7,26) 48,79 (7,46) 0,101 Sleep efficiency % 91.00 (1.78) 88.56 (2.15) 0.126 Sleep latency 16,75 (2,67) 22,46 (6,16) 0,359 Latency of SWS 10,75 (0,93) 11,46 (2,12) 0,767 Latency of REM 87,64 (9,36) 107,11(14,38) 0,240 Stage 1 15,39 (1,92) 29,57 (4,09) 0,002 Stage 2 205,86 (8,82) 231,32 (9,10) 0,036 SWS 104,71 (6,62) 48,18 (5,16) <0,001 REM 92,29 (6,59) 87,00 (9,03) 0,393 Figure 2. OGTT data: blood glucose level in fasting state, in 1 hour and 2 hours after glucose intake. In session with SWS suppression glucose level 1h after glucose intake was significantly greater than in control one (p=0,035). Figure 3. Salivary melatonin concentrations in the two experimental sessions. SWS suppression did not significantly influence night melatonin concentrations. However, it led to an increase of melatonin level in the morning immediately after awakening (p=0,002). SWS suppression reduced the time spent in SWS by 56.53 min (54 %) without essential changes in total sleep time and sleep efficiency. Conclusions Slow-wave sleep suppression affected glucose tolerance the following morning and led to an increase of melatonin level immediately after awakening. Considering the influence of melatonin on the circadian profile of insulin secretion and action, we may assume that changes of melatonin concentration as a result of disturbed sleep could lead to impairment of glucose tolerance. Acknowledgements: The study was supported by a grant of Russian Foundation for Basic Research (RFBR grant number 18-013-01187 А). Contact e-mail: ukraintseva@yandex.ru