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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-5)
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University of Chicago
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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
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