There is convincing evidence that, in humans, discrete sleep stages are important for daytime brain function, but whether any particular sleep stage has functional significance for the rest of the body is not known. Deep non-rapid eye movement (NREM) sleep, also known as slow-wave sleep (SWS), is thought to be the most ''restorative'' sleep stage, but beneficial effects of SWS for physical well being have not been demonstrated. The initiation of SWS coincides with hormonal changes that affect glucose regulation, suggesting that SWS may be important for normal glucose tolerance. If this were so, selective suppression of SWS should adversely affect glucose homeostasis and increase the risk of type 2 diabetes. Here we show that, in young healthy adults, all-night selective suppression of SWS, without any change in total sleep time, results in marked decreases in insulin sensitivity without adequate compensatory increase in insulin release, leading to reduced glucose tolerance and increased diabetes risk. SWS suppression reduced delta spectral power, the dominant EEG frequency range in SWS, and left other EEG frequency bands unchanged. Importantly, the magnitude of the decrease in insulin sensitivity was strongly correlated with the magnitude of the reduction in SWS. These findings demonstrate a clear role for SWS in the maintenance of normal glucose homeostasis. Furthermore, our data suggest that reduced sleep quality with low levels of SWS, as occurs in aging and in many obese individuals, may contribute to increase the risk of type 2 diabetes.aging ͉ sleep quality ͉ sleep disordered breathing ͉ delta waves ͉ insulin resistance H uman sleep is composed of rapid-eye-movement (REM) sleep and stages 1, 2, 3, and 4 of non-REM (NREM) sleep. The deeper stages of NREM sleep, i.e., stages 3 and 4, also known as slow-wave sleep (SWS), are thought to be the most ''restorative.'' There is indeed evidence that SWS plays a role in waking neurobehavioral function (1), particularly in memory consolidation (2, 3), but whether SWS is also important for peripheral physiological function is not known. The initiation of SWS is temporally associated with transient metabolic, hormonal, and neurophysiologic changes, all of which could potentially affect glucose homeostasis. These include decreased brain glucose utilization, stimulation of growth hormone release, inhibition of corticotropic activity, decreased sympathetic nervous activity, and increased vagal tone. We therefore hypothesized that SWS plays a role in glucose regulation and that suppression of SWS may adversely affect glucose homeostasis.To test this hypothesis, we developed an experimental model in young healthy lean individuals that was designed to selectively suppress SWS and assessed the impact of this intervention on glucose homeostasis. The EEG was continuously monitored, and SWS was suppressed by delivering acoustic stimuli of varying frequencies and intensities. The intervention was designed to substitute deep NREM sleep, i.e., stages 3 and 4, with shallow NREM slee...