Regulation of peripheral glucose levels during human sleep

Studies in rats indicate that oscillatory signatures of memory processing during sleep, specifically hippocampal sharp wave-ripples, also regulate peripheral glucose concentration. Here, we examined whether there is a similar link between such signatures of memory processing and glucose regulation during sleep in healthy humans. We obtained polysomnographic recordings and continuous recordings of peripheral interstitial glucose levels (1 sample/minute) from 10 participants (5 females) during two consecutive nights. Temporal relationships between electroencephalography (EEG) events of interest and glucose levels were examined using cross-correlation functions and peri-event time histograms. Confirming the findings in rats, we found that sleep spindles, a core signature of sleep-dependent memory processing, were followed within 1-6 minutes by a robust decrease in glucose concentrations. By contrast, slow oscillation events hallmarking slow wave sleep were followed, with a lag of 5-11 minutes, by an increase in glucose levels. Transitions into rapid eye movement sleep were followed by a glucose decrease after 10-14 minutes, whereas awakenings and microarousals were linked to immediate glucose increases. These temporal relationships indicate a sleep-specific regulation of peripheral glucose concentrations that is linked to both signatures of sleep-dependent memory processing as well as the macro-architecture of sleep. They possibly reflect noradrenergic regulation of sympathetic activity via the brainstem locus coeruleus and may be of relevance in clinical conditions with concurrent disturbances of sleep and glucose regulation.