Increased Morning Cortisol Level: Effect of Sleep Fragmentation or Stress Response to the Last Annoying Stimulus?

Abstract

Fragmented sleep has great effects on daily life, including sleepiness, impaired cognitive function, decreased mood, and elevated BP.1Kingshott RN Cosway RJ Deary IJ Douglas NJ The effect of sleep fragmentation on cognitive processing using computerized topographic brain mapping.J Sleep Res. 2000; 9: 353-357Crossref PubMed Scopus (57) Google Scholar, 2Morrell MJ Finn L Kim H Peppard PE Badr MS Young T Sleep fragmentation, awake blood pressure, and sleep-disordered breathing in a population-based study.Am J Respir Crit Care Med. 2000; 162: 2091-2096Crossref PubMed Scopus (121) Google Scholar, 3Stepanski EJ The effect of sleep fragmentation on daytime function.Sleep. 2002; 25: 268-276Crossref PubMed Scopus (192) Google Scholar In an excellent study in a recent issue of CHEST (January 2010), Stamatakis and Punjabi4Stamatakis KA Punjabi NM Effects of sleep fragmentation on glucose metabolism in normal subjects.Chest. 2010; 137: 95-101Abstract Full Text Full Text PDF PubMed Scopus (421) Google Scholar show that two nights of nonspecific sleep fragmentation in healthy volunteers led to decreased insulin sensitivity and glucose effectiveness despite normal sleep duration. This study helps to elucidate the influence of sleep fragmentation per se on glucose metabolism without the confounding effect of sleep duration or hypoxic insult, as seen in the case of obstructive sleep apnea. The authors concluded that increased sympathetic activity and adrenocortical activity likely mediate the adverse effects of poor sleep quality, based on the finding of increased morning cortisol levels and increased sympathetic activity. They used auditory and mechanical stimuli to elicit EEG microarousals with a frequency of ≥ 30 events/h. If the stimuli failed, the subsequent stimulus got larger by increasing the tone volume of auditory stimuli or combining the two kinds of stimulus. In this study, most of the stimuli were effective, including the last one at the end of the sleep period, which was probably the largest stimulus in intensity. When a human is exposed to noxious or potentially noxious stimuli, there is an increased secretion of corticotropin and, consequently, a rise in the circulating cortisol. Approximately 90% to 95% of the cortisol in the plasma binds to plasma proteins, which slows the elimination of cortisol from the plasma. Therefore, cortisol has a relatively long half-life of 60 to 90 min and thus a lasting action.5Guyton AC Hall JE Guyton & Hall Textbook of Medical Physiology. 11th ed. Saunders, Philadelphia, PA2006: 947Google Scholar An increased morning cortisol level (measured at 8:00 am in this study) may be the consequence of the last effective stimulus, elicited 1 or 2 h prior to measurement, rather than that of sleep fragmentation. As the authors stated, elevations of cortisol, even within the normal physiologic range, can decrease insulin sensitivity, enhance hepatic gluconeogenesis, and inhibit insulin secretion.6Andrews RC Walker BR Glucocorticoids and insulin resistance: old hormones, new targets.Clin Sci (Lond). 1999; 96: 513-523Crossref PubMed Scopus (595) Google Scholar To settle this dispute, one additional night of nonfragmented sleep following the two nights of fragmented sleep is needed as a sleep-recovery period, as stated in some sleep deprivation studies.7Follenius M Brandenberger G Bandesapt JJ Libert JP Ehrhart J Nocturnal cortisol release in relation to sleep structure.Sleep. 1992; 15: 21-27Crossref PubMed Scopus (145) Google Scholar, 8Spiegel K Leproult R Van Cauter E Impact of sleep debt on metabolic and endocrine function.Lancet. 1999; 354: 1435-1439Abstract Full Text Full Text PDF PubMed Scopus (2723) Google Scholar, 9Akerstedt T Palmblad J de la Torre B Marana R Gillberg M Adrenocortical and gonadal steroids during sleep deprivation.Sleep. 1980; 3: 23-30Crossref PubMed Scopus (81) Google Scholar In addition, one single stimulus is given near the end of the night, which is of the same intensity and timing as the last stimulus in the previous night of sleep fragmentation. If an elevated cortisol level is still observed in the coming morning (day 5), the disturbed glucose metabolism may not be attributed to the effect of sleep fragmentation. Besides, evening cortisol concentration following sleep deprivation was raised in sleep deprivation studies, reflecting an impairment of negative feedback control of the hypothalamo-pituitary-adrenal axis.8Spiegel K Leproult R Van Cauter E Impact of sleep debt on metabolic and endocrine function.Lancet. 1999; 354: 1435-1439Abstract Full Text Full Text PDF PubMed Scopus (2723) Google Scholar, 10Leproult R Copinschi G Buxton O Van Cauter E Sleep loss results in an elevation of cortisol levels the next evening.Sleep. 1997; 20: 865-870PubMed Google Scholar This finding was not observed in this study, suggestive of a different mechanism underlying sleep deprivation and sleep fragmentation, or just an unequal stress in intensity, which deserves further exploring.