Chronic sleep loss, obesity and sleep-disordered breathing (SDB) are increasingly common in industrialized countries. Sleep curtailment in healthy young lean adults results in the development of components of the metabolic syndrome, including reduced glucose tolerance and/or insulin resistance, elevated evening cortisol levels, increased cardiac sympatho-vagal balance, and a risk of weight gain resulting from reduced leptin levels and increased hunger and appetite. The studies proposed in the present application build on novel findings from our group that indicate that obese individuals may be more at risk for further weight gain than lean individuals in conditions of sleep loss, and that individuals levels of slow wave activity (SWA), a stable trait-dependent marker of deep sleep, may predict subjective vulnerability to sleep loss, and are also likely to predict the severity of adverse metabolic and cardiovascular consequences of sleep loss. We therefore propose to characterize sleep architecture, autonomic nervous system (ANS) activity, and biomarkers of the metabolic syndrome in three groups of middle aged (35-50 years old) subjects studied while they follow their usual sleep habits as well as during 4 days of sleep restriction and sleep extension, presented in randomized order in a cross-over design. The three groups of subjects will be healthy lean men and women, gender-matched individuals who are obese, and gender-matched individuals who are obese and also suffer from SDB.
The specific aims are: 1. To test the hypothesis that baseline levels of SWA are lower in obese adults than in lean controls, and are even lower in obese subjects with SDB, and examine correlations between levels of SWA and sleep duration, ANS activity and biomarkers of the metabolic syndrome. 2. To test the hypothesis that sleep restriction, as compared to sleep extension, has adverse effects on biomarkers of the metabolic syndrome in lean adults, obese adults, and obese adults with SDB. 3. To test the hypothesis that the adverse impact of partial sleep loss on components of the metabolic syndrome is more important for obese adults than in lean adults, and more severe in obese adults with SDB than in those without SDB. This project capitalizes on our experience with human studies of """"""""sleep debt"""""""" and on our extensive expertise in assessment of ANS activity to evaluate the role of the ANS as a mediator of the adverse health effects of chronic sleep loss.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL075025-01
Application #
6707267
Study Section
Special Emphasis Panel (ZHL1-CSR-P (S1))
Program Officer
Twery, Michael
Project Start
2003-09-30
Project End
2007-07-31
Budget Start
2003-09-30
Budget End
2004-07-31
Support Year
1
Fiscal Year
2003
Total Cost
$297,000
Indirect Cost
Name
Free University of Brussels
Department
Type
DUNS #
371781076
City
Brussels
State
Country
Belgium
Zip Code
Temple, Karla A; Leproult, Rachel; Morselli, Lisa et al. (2018) Sex Differences in the Impact of Obstructive Sleep Apnea on Glucose Metabolism. Front Endocrinol (Lausanne) 9:376
Guyon, Aurore; Morselli, Lisa L; Balbo, Marcella L et al. (2017) Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men. Sleep 40:
Grimaldi, Daniela; Beccuti, Guglielmo; Touma, Carol et al. (2014) Association of obstructive sleep apnea in rapid eye movement sleep with reduced glycemic control in type 2 diabetes: therapeutic implications. Diabetes Care 37:355-63
Copinschi, Georges; Leproult, Rachel; Spiegel, Karine (2014) The important role of sleep in metabolism. Front Horm Res 42:59-72
Morselli, Lisa L; Guyon, Aurore; Spiegel, Karine (2012) Sleep and metabolic function. Pflugers Arch 463:139-60
Spiegel, Karine; Tasali, Esra; Leproult, Rachel et al. (2011) Twenty-four-hour profiles of acylated and total ghrelin: relationship with glucose levels and impact of time of day and sleep. J Clin Endocrinol Metab 96:486-93
Morselli, Lisa; Leproult, Rachel; Balbo, Marcella et al. (2010) Role of sleep duration in the regulation of glucose metabolism and appetite. Best Pract Res Clin Endocrinol Metab 24:687-702
Leproult, Rachel; Van Cauter, Eve (2010) Role of sleep and sleep loss in hormonal release and metabolism. Endocr Dev 17:11-21
Spiegel, Karine; Tasali, Esra; Leproult, Rachel et al. (2009) Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol 5:253-61
Van Cauter, Eve; Holmback, Ulf; Knutson, Kristen et al. (2007) Impact of sleep and sleep loss on neuroendocrine and metabolic function. Horm Res 67 Suppl 1:2-9

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