Clinical trial NCT06809023: Evaluation of Sex Differences in Glucose Metabolism in Response to Sleep Curtailment
Official title: Evaluation of Sex Differences in Glucose Metabolism in Response to Sleep Curtailment
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Sleep Deprivation
Sex Differences
Glucose Tolerance
Keywords: glucose metabolism
sleep deprivation
sex differences
GLP-1
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2025-02-05
Enrollment: 32
Sex: ALL
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study uses a within-subjects randomized crossover design to compare the effects of sleep restriction to a control condition where participants are not sleep restricted.
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this study is to learn whether insufficient sleep affects glucose metabolism differently in healthy men and women.

Detailed description: Two-thirds of Americans report regularly obtaining an insufficient amount of sleep. Chronic sleep deficiency is associated with negative health consequences such as obesity, cardiovascular disease, diabetes, and metabolic syndrome. Laboratory studies have shown that sleep restriction reduces glucose tolerance in otherwise healthy adults, and it is now well established that sleep restriction decreases insulin sensitivity. However, there is a significant gap in the literature regarding how sex differences may drive disparate metabolic outcomes in men and women in response to sleep loss.

Epidemiological studies strongly suggest that women and men may respond differently to the physiological challenges associated with sleep restriction and circadian disruption. Trouble sleeping is more prevalent in women compared to men, and sleep disturbances appear to be associated with higher risk of obesity, hypertension, and elevated HbA1c in women compared to men. Although multiple causative mechanisms have been explored, most laboratory studies investigating the mechanisms by which sleep disturbances impair metabolism have been conducted solely in men or have not been powered for sex differences.

One potential mechanism underlying sex differences in glucose regulation after sleep loss is the glucagon-like peptide-1 (GLP-1) pathway. GLP-1 reduces blood glucose by stimulating insulin secretion and inhibiting glucagon secretion in response to food intake and is the target of promising new treatments for insulin resistance and obesity such as Ozempic and Wegovy. Interestingly, women exhibit a greater response to treatment with these GLP-1 receptor agonist drugs; additionally, one laboratory study found decreased GLP-1 levels in women but not in men after 4 days of sleep curtailment.

This study will use a randomized crossover design in young men and premenopausal women to test the hypotheses that sleep loss impairs glucose tolerance more in women than in men, and that this difference is partially mediated by sex-dependent responses in GLP-1 after sleep curtailment.

Currently, there are no sex-specific recommendations for management of diabetes or sleep loss, despite evidence that women may bear a greater disease burden than men. Understanding sex differences in glucose metabolism in response to sleep curtailment is critical for making more effective and individualized treatment recommendations to mitigate the adverse metabolic effects of sleep restriction in women and men.

Eligibility criteria: Inclusion Criteria:

* Healthy adults with conventional sleep-wake timing
* Non-smokers
* Completion of medical, psychological, and sleep screening tests
* Able to spend 5 consecutive days/nights in the laboratory on two separate occasions (total of 10 days/nights in the laboratory)
* Women must have a recent history of regular menstrual cycles

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 including hormonal birth control
* 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 year
* Hearing impairment, visual impairment
* History of eye trauma or surgery
* Drug or alcohol dependency

Primary outcomes:
measure: Difference between men and women in postprandial glucose response after Sleep Restriction
timeFrame: Study Day 4 (Arm 1) vs. Study Day 4 (Arm 2)
measure: Difference between men and women in postprandial GLP-1 response after Sleep Restriction
timeFrame: Study Day 4 (Arm 1) vs. Study Day 4 (Arm 2)
Secondary outcomes:
measure: Difference between men and women in fasting glucose after Sleep Restriction
timeFrame: Study Day 5 (Arm 1) vs. Study Day 5 (Arm 2)
measure: Difference between men and women in fasting GLP-1 after Sleep Restriction
timeFrame: Study Day 5 (Arm 1) vs. Study Day 5 (Arm 2)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
References: