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

Not Applicable

Completed

Conditions: Glucose Intolerance
Sleep Deprivation
Sleep

Registration Number: NCT04868539

Lead Sponsor: Brigham and Women's Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Impairment of Insulin Sensitivity	Change between Study Day 7 vs. Study Day 15 and Study Day 24 vs. Study Day 32	Insulin sensitivity (Si) is assessed via minimal model analysis, a mathematical model developed by Bergman and colleagues. Higher values represent better insulin sensitivity and lower values represent impaired insulin sensitivity. The mean change in Si between exposure and baseline is reported for each arm.
Impairment of Glucose Tolerance	Change between Study Day 6 vs. Study Day 14 and Study Day 23 vs. Study Day 31	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 area under the curve from minutes 0-120 following a mixed meal tolerance test
Duration of Nocturnal Melatonin Secretion	Change between Study Day 14-15 (overnight) vs. Study Day 31-32 (overnight)	Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will acutely 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 a threshold calculated as 25% of peak-to-trough amplitude at baseline in dim light.

Secondary Outcome Measures

Name	Time	Method
Acute Insulin Response to Glucose	Change from study day 7 to 15 compared to change from study day 24 to 32	Acute Insulin Response as calculated with minimal model analysis, a mathematical model developed by Bergman and colleagues, and represents early insulin release in the body to manage blood glucose levels. Higher values represent a better response and lower values represent a worse response. The mean change in AIRg between exposure and baseline is reported for each arm.
Glucose Effectiveness	Change from study day 7 to 15 vs change from study day 24 to 32	Glucose Effectiveness as calculated using minimal model analysis, a mathematical model developed by Bergman and colleagues. It represents how well the body can normalize blood glucose independent of insulin. Higher glucose effectiveness (Sg) is generally associated with better metabolic health outcomes.
Insulin Area-under-the-curve	Change between Study Day 6 vs. Study Day 14 and Study Day 23 vs. Study Day 31	Insulin area under the curve (AUC) as calculated with trapezoidal method between 0-120min following mixed meal tolerance test.
Duration of Endogenous Melatonin Secretory Profile	Study Day 15-16 vs Study Day 32-33	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 the endogenous melatonin secretory profile 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 a threshold calculated as 25% of peak-to-trough amplitude at baseline in dim light.

Trial Locations

Locations (1): Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States