Individual Differences in Diabetes Risk: Role of Sleep Disturbances

Principal Investigator: VAN CAUTER, EVE
Institution Receiving Award: CHICAGO, UNIVERSITY OF
Program: PRMRP
Proposal Number: PR064727
Award Number: W81XWH-07-2-0071
Funding Mechanism: Investigator-Initiated
Partnering Awards:
Award Amount: $667,726.00


Chronic partial sleep loss, due to bedtime restriction, is increasingly prevalent in modern society. Active duty army personnel are overexposed to chronic partial sleep deprivation because of the demands of continuous or extended operations and training. During the past few years, evidence from both laboratory and epidemiological studies has accumulated to indicate that decreased sleep duration has an adverse effect on glucose regulation and on the neuroendocrine control of appetite and may increase the risk of obesity and type 2 diabetes. Taken together, the findings suggest that chronic partial sleep deprivation may be involved in the current epidemic of obesity and diabetes. Based on laboratory studies of sleep restriction, our group has obtained strong evidence for the existence of large individual differences in metabolic vulnerability to sleep loss. In pioneering studies of similar design, the group led by Dr. Balkin in the Department of Behavioral Biology at Walter Reed Army Institute of Research (WRAIR) has demonstrated the degradation of cognitive performance during chronic partial sleep restriction and observed individual differences in cognitive vulnerability to sleep loss. Recent studies have indicated a role for slow-wave sleep in learning and memory and it is possible that individual differences in diabetes risk related to slow-wave activity reflect a trait-like, general sensitivity to the effects of sleep loss, and may therefore also be predictive of individual differences in cognitive vulnerability.

We have recently obtained exciting preliminary data that suggest that a specific stable heritable trait of the sleep electroencephalogram (EEG), known as slow-wave activity (SWA), accounts for the majority of individual variability in the adverse effects of sleep loss on diabetes risk. The present proposal seeks to identify SWA as a predictor of diabetes risk associated with sleep loss in a subject population matching the gender, ethnic, and age distribution of active duty army personnel (n=63) and to test the hypothesis that individuals with low SWA (n=16) are at much higher risk for developing diabetes following chronic partial sleep restriction than those with higher SWA (n=16). The laboratory study will compare 5 days of bedtime restriction (4.5 hours per night) to 5 days of normal bedtimes (8.5 hours per night) in a randomized crossover design. Diabetes risk will be evaluated at the end of each condition by the glucose disposition index (DI) as derived from a frequently sampled intravenous glucose tolerance test. Alterations in glucose tolerance in the course of each study will be followed with a continuous glucose monitoring system using a subcutaneous sensor providing 288 glucose measurements per 24 hours. The wake EEG and estimations of cardiac sympatho-vagal balance will be obtained in the morning, afternoon, and evening on each day of each study. Subjective ratings of alertness, mood, hunger, and appetite and performance on a battery of cognitive tests used by WRAIR will be recorded three times daily. Individual differences in diabetes risk and cognitive performance will be evaluated and related to individual differences in baseline SWA.

The proposed project builds on the joined expertise of the University of Chicago and WRAIR in well-controlled studies of partial chronic sleep restriction in humans to try to identify individuals who may be more at risk to develop obesity and diabetes when exposed to recurrent sleep loss. While individual differences in vulnerability to sleep loss have been well documented for cognitive function, very little is known about individual differences in metabolic vulnerability to sleep loss. The proposed work will greatly advance our understanding of these differences and will provide the basis for the design of countermeasures to the deleterious effects of sleep loss on metabolism. Such countermeasures could include more frequent and/or more extended recovery nights, increased physical exercise to avoid the reduction in insulin sensitivity associated with sleep loss, limitations on frequency, duration, and severity of sleep restriction and recommendations regarding sleep hygiene as an adjuvant to strategies for avoiding weight gain.