instructions): Aging is typically associated with high risk of type 2 diabetes and low levels of slow wave sleep (SWS). We have shown that in healthy young adults, experimental suppression of SWS results in marked decreases in insulin sensitivity, without adequate increase in insulin release, leading to reduced glucose tolerance and increased diabetes risk. Low levels of SWS achieved in our studies were similar to that occurs in aging. Importantly, the individuals who had low levels of SWS at baseline had the largest decrements in insulin sensitivity, suggesting that there might be a predisposition to develop diabetes when SWS deteriorates. These findings raise two important questions: 1) Are older adults predisposed to diabetes risk more than the younger individuals when SWS deteriorates? 2) Does preservation or restoration of SWS has beneficial effects on glucose metabolism and thus may reduce the diabetes risk in older adults? The overall goal of this project is to address these questions and to investigate the role of SWS in the risk for diabetes in older adults. We will study healthy young and older adults under controlled laboratory conditions with 3 nights of undisturbed sleep, 3 nights of SWS suppression, and 3 nights REM fragmentation and test the hypothesis that SWS suppression results in higher diabetes risk in older compared to young adults (AimD. We will study older adults with obstructive sleep apnea (OSA), a highly prevalent sleep disorder that results in low levels of SWS and that is linked to diabetes, and test the hypothesis that continuous positive airway pressure (CPAP) treatment of OSA has rapid beneficial effects on glucose metabolism (Aim2) and dissect the role of SWS in mediating these metabolic effects (Aim3). Older adults with OSA will be studied in the laboratory for 9 consecutive days under 3 conditions: before treatment, with effective CPAP treatment, and with CPAP treatment with experimental suppression of SWS. These studies will combine assessments of glucose metabolism by intravenous glucose tolerance testing, continuous glucose monitoring via subcutaneous sensors, invitro studies of insulin signaling in adipocytes from fat biopsies, measurements of diabetes-related factors, estimations of sympathovagal balance, quantification of body fat, and neurobehavioral measures.

Public Health Relevance

Type 2 diabetes is a public health and economic concern in the aging population and is associated with increased morbidity and mortality. The information gained from these studies may provide novel insights into the mechanisms that links alterations in sleep quality in older adults to abnormalities in glucose metabolism and increased risk for diabetes, and may thus have important preventive and therapeutic implications in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG011412-17
Application #
8448185
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
$249,457
Indirect Cost
$88,676
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

Showing the most recent 10 out of 206 publications