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

Brigham and Women's Hospital14 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Glucose Intolerance Sleep Deprivation Sleep

Interventions

Sleep Restriction with ALAN first, then Sleep Restriction without ALANOTHER

Sleep restriction with 90 lux lighting for 19hr/day first, followed by Sleep restriction with 90 lux lighting for 14hr/day

Sleep Restriction without ALAN first, then sleep restriction with ALANOTHER

Sleep restriction with 90 lux lighting for 14hr/day first, followed by Sleep restriction with 90 lux lighting for 19hr/day

Eligibility

Sex: ALLMin age: 20 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Brigham and Women's Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Impairment of Insulin Sensitivity

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.

Time frame: 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 area under the curve from minutes 0-120 following a mixed meal tolerance test

Time frame: 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 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.

Time frame: Change between Study Day 14-15 (overnight) vs. Study Day 31-32 (overnight)

Secondary Outcomes

Acute Insulin Response to Glucose

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.

Data from ClinicalTrials.gov

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