Our group has identified reduced sleep duration and reduced sleep quality as novel risk factors for type 2 diabetes. Type 2 diabetes develops when the pancreatic beta cells fail to release enough insulin to compensate for the degree of insulin resistance of peripheral tissues. Reductions in sleep duration or in sleep quality both result in increased insulin resistance without appropriate compensation by beta cell release. We have further obtained evidence indicating that beta cell function in young healthy adults is strongly correlated with baseline levels of slow-wave activity (SWA;EEG spectral power in the 0.5-4 Hz range), the primary marker of sleep-wake homeostasis. Studies completed during the previous grant period have, however, shown that during repeated partial sleep deprivation, SWA does not increase despite the increased cumulated duration of wakefulness. This """"""""allostasis"""""""" of SWA with recurrent sleep loss could accelerate age-related declines in the homeostatic control of sleep. SWA decreases markedly with age and sex differences have been well-recognized. We have recently identified robust ethnic differences in SWA, with African-Americans having lower levels of SWA than whites. SWA is a remarkably stable trait-dependent characteristic that varies greatly from one individual to another. Heritability of SWA has not yet been evaluated. The overall goal of this project is to test the hypothesis that individuals with low SWA, because of age, ethnicity, sex or genetic factors, are more susceptible to develop type 2 diabetes because they have reduced beta cell function and, therefore a higher vulnerability to the metabolic challenge of sleep disturbances. To achieve this goal, we will combine statistical analyses of the very large data base accumulated from studies conducted by our group during the past 10 years, with a direct experimental approach and an exploration of genetic factors that could underlie both the regulation of SWA and genetic susceptibility to diabetes. The findings from this project are expected to demonstrate the importance of preserving or improving sleep quality to reduce the risk of type 2 diabetes.

Public Health Relevance

The incidence of type 2 diabetes is increasing in the U.S. and worldwide. This project will determine the role of reductions in sleep duration and quality in the risk of type 2 diabetes. The findings could lead to novel strategies to delay the development or reduce the severity of type 2 diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG011412-17
Application #
8448187
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
17
Fiscal Year
2013
Total Cost
$250,351
Indirect Cost
$89,869
Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Morselli, Lisa L; Gamazon, Eric R; Tasali, Esra et al. (2018) Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study. Diabetes 67:155-164
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
Morselli, Lisa L; Temple, Karla A; Leproult, Rachel et al. (2018) Determinants of Slow-Wave Activity in Overweight and Obese Adults: Roles of Sex, Obstructive Sleep Apnea and Testosterone Levels. Front Endocrinol (Lausanne) 9:377
Jiang, Peng; Turek, Fred W (2018) The endogenous circadian clock programs animals to eat at certain times of the 24-hour day: What if we ignore the clock? Physiol Behav 193:211-217
Hong, Hee-Kyung; Maury, Eleonore; Ramsey, Kathryn Moynihan et al. (2018) Requirement for NF-?B in maintenance of molecular and behavioral circadian rhythms in mice. Genes Dev 32:1367-1379
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:
Baron, Kelly Glazer; Reid, Kathryn J; Malkani, Roneil G et al. (2017) Sleep Variability Among Older Adults With Insomnia: Associations With Sleep Quality and Cardiometabolic Disease Risk. Behav Sleep Med 15:144-157
Peek, Clara Bien; Levine, Daniel C; Cedernaes, Jonathan et al. (2017) Circadian Clock Interaction with HIF1? Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle. Cell Metab 25:86-92
Mokhlesi, Babak; Grimaldi, Daniela; Beccuti, Guglielmo et al. (2017) Effect of one week of CPAP treatment of obstructive sleep apnoea on 24-hour profiles of glucose, insulin and counter-regulatory hormones in type 2 diabetes. Diabetes Obes Metab 19:452-456
Jiang, Peng; Turek, Fred W (2017) Timing of meals: when is as critical as what and how much. Am J Physiol Endocrinol Metab 312:E369-E380

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