Influence of Nocturnal Light Exposure on the Impairment of Glucose Tolerance Induced by Chronic Sleep Restriction

Study Overview
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Brief Summary
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This project is designed to test for the first time whether glucose metabolism is differentially impaired by sleep restriction with and without additional exposure to artificial light at night (ALAN).

Detailed Description
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Laboratory studies have shown that sleep restriction to 4-6h per night for durations varying from one to 14 days reduces glucose tolerance in otherwise healthy adults, but the mechanisms by which insufficient sleep impairs glucose metabolism are still unknown. Current theories are based on the premise that the adverse metabolic consequences are caused by reduction in the duration of sleep per se. However, sleep curtailment is typically accompanied by longer exposure to artificial light at night (ALAN), which is an environmental endocrine disrupter that profoundly disrupts circadian rhythms. The investigators have previously reported that acute circadian misalignment induced hyperglycemia comparable to pre-diabetic states in a third of otherwise healthy participants. Since then, the investigators have shown that even when the circadian phase of participants was realigned, prior exposure to 2 ½ weeks of chronic sleep restriction combined with a history of recurrent circadian disruption induced even more deleterious effects on glucose metabolism, in which pancreatic beta cells failed to respond adequately to increased glucose levels. Moreover, both night and rotating shift work (which induce circadian disruption) are associated with increased risk for metabolic problems. Night shifts can lead to acute increases in glucose and insulin levels, although some studies report reduced insulin release in response to meals consumed during the night. Given that circadian disruption has been shown to independently adversely affect metabolism, and exposure to ALAN adversely impacts metabolism in animals, it is important to understand the extent to which circadian disruption contributes to the observed impact of sleep curtailment on metabolism. No previous studies of the metabolic impact of sleep restriction in humans have controlled for this additional exposure to ALAN, thus confounding the effects of sleep restriction with the effects of circadian disruption caused by extended exposure to ALAN.

Official Title
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Influence of Nocturnal Light Exposure on the Impairment of Glucose Tolerance Induced by Chronic Sleep Restriction

Conditions
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Sleep, Glucose Intolerance, Sleep Deprivation

Intervention / Treatment
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* Other: Artificial Light At Night
* Behavioral: Sleep Restriction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults with conventional and regular sleep-wake timing Non-smokers Completion of medical, psychological, and sleep screening tests Able to spend 33 consecutive days/nights in the laboratory Normal color vision Exclusion Criteria: History of neurological or psychiatric disorder History of sleep disorder or regular use of sleep-promoting medication Current prescription, herbal, or over-the-counter medication use Traveling across 2 or more time zones within past 3 months Donating blood within past 8 weeks Worked night or rotating shift work within past 3 years Hearing impairment, visual impairment History of eye trauma or surgery Drug or alcohol dependency

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study uses a within-subjects randomized crossover design to compare the effects of sleep restriction with and without ALAN on glucose metabolism. The order in which subjects undergo the two sleep interventions will be randomized.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep Restriction with Extended Duration Artificial Light at Night (ALAN)<br>In the Sleep Restriction Group with Extended Duration Artificial Light At Night (ALAN) first, the sleep episodes will be shortened to 5 hours, centered at the same time as the baseline sleep (with bedtime 2.5 hours later and wake time 2.5 hours earlier). | Other: Artificial Light At Night<br>* 90 lux lighting for 19hr/day<br>* Other names: ALAN;Behavioral: Sleep Restriction<br>* 5-hr of sleep/night<br>|
| Experimental: Sleep Restriction without Extended Duration Artificial Light at Night (ALAN)<br>In the Sleep Restriction group without Extended Duration ALAN, the sleep episodes will be shortened to 5 hours as in the ALAN Condition (centered at the same time as the baseline sleep with bedtime 2.5 hours later and wake time 2.5 hours earlier), but the participant will remain sitting in bed in near darkness (< 1 lux) for the 2.5 hours before and after the 5-hour sleep episode, such that their exposure to room lighting and activity (14 hours/day) will remain similar to that in the Baseline condition. | Behavioral: Sleep Restriction<br>* 5-hr of sleep/night<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impairment of Insulin Sensitivity | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (Artificial Light at Night) (LD 19:5) will induce greater impairment of insulin sensitivity (Si), as assessed by an intravenous glucose tolerance test (IVGTT), than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Insulin sensitivity will be assessed via minimal model analysis. | Change between Study Day 7 vs. Study Day 15 and Study Day 24 vs. Study Day 32 | 
| Impairment of Glucose Tolerance | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will induce greater impairment of glucose tolerance than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Glucose tolerance will be calculated as the rate of glucose disposal over the first 20 minutes after glucose administration. | Change between Study Day 6 vs. Study Day 14 and Study Day 23 vs. Study Day 31 | 
| Duration of Nocturnal Melatonin Secretion | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will reduce the duration of nocturnal melatonin secretion as compared to baseline more than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Duration of nocturnal melatonin secretion will be determined by the duration of time at which melatonin levels are above 25% of their nightly peak levels. | Change between Study Day 15-16 vs. Study Day 32-33 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of long-chain highly unsaturated triglycerides | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will lead to a greater reduction in the levels of long-chain highly unsaturated triglycerides than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). We will use liquid chromatography-mass spectrometry to detect lipids of interest. We will focus on triglycerides associated with diabetes risk (e.g. TG44:1, TG46:1, etc.) | Change between Study Day 7 vs. Study Day 15 and Study Day 24 vs. Study Day 32 | 
| Proteomic Profile | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will lead to a change in the proteomic profile compared with exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Blood samples will undergo multiplexed proteomic profiling to search for proteins that are reliably increased or decreased following sleep restriction with ALAN compared to sleep restriction without ALAN. | Change between Study Day 7 vs. Study Day 15 and Study Day 24 vs. Study Day 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Sleep Restiction, Artificial Light At Night, Glucose Intolerance, Melatonin, Sleep