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Inadequate sleep is an independent risk factor for metabolic abnormalities (such as obesity, insulin resistance, and hyperglycemia). Women report sleep disruption during the menopause transition (perimenopause) and into the postmenopausal years. Sleep disruption is one of the primary reasons why midlife women seek medical care, with up to 60% reporting significant sleep disturbances (e.g., trouble falling asleep, early morning waking, and hot flashes/night sweats). Despite the majority of women experiencing sleep disruption, no study has investigated the molecular mechanisms linking sleep disruption and the changes in metabolism that coincide with menopause.
The investigators will conduct a randomized, crossover trial investigating the effect of sleep restriction compared to habitual sleep on adipose tissue and skeletal muscle insulin sensitivity in vivo and ex vivo. The investigators will randomize up to 10 healthy postmenopausal women with overweight/obesity and ≥6.5 hours of self-reported habitual nightly sleep to 4 nights of each sleep condition (sleep restriction and habitual sleep). After the fourth night of each sleep condition, the investigators will administer a two-step hyperinsulinemic-euglycemic clamp and collect skeletal muscle and adipose tissue samples prior to insulin infusion.
The overarching hypothesis is that sleep restriction will reduce skeletal muscle and adipose tissue insulin sensitivity compared to habitual sleep.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sleep Restriction | Experimental | Women will undergo 4 nights of sleep restriction treatment. |
|
| Habitual Sleep | Experimental | Women will undergo 4 nights of habitual sleep treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sleep Restriction | Behavioral | Women will be undergo 4 nights of sleep restriction. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose infusion rate (via 2-step hyperinsulinemic-euglycemic clamp) (in vivo) | Insulin sensitivity by a 2-step hyperinsulinemic euglycemic clamp is performed at the end sleep conditions. | 4 days |
| Measure | Description | Time Frame |
|---|---|---|
| Adipose tissue insulin sensitivity (via free fatty acid area-under-the-curve during the low-dose clamp) (in vivo) | During the low-dose insulin portion of the hyperinsulinemic-euglycemic clamp, free fatty acids will be samples across a 3-hour period to quantify a surrogate measure of adipose tissue insulin sensitivity in vivo. | 4 days |
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INCLUSION CRITERIA:
EXCLUSION CRITERIA:
Sporadic use of certain medications is fine (however, enrollment will depend on a case-by-case basis). If taking sporadically, women should not be taking the medication for 1-month prior to the first Run-In period.
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| Name | Affiliation | Role |
|---|---|---|
| Kara L Marlatt, PhD, MPH | Pennington Biomedical Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pennington Biomedical Research Center | Baton Rouge | Louisiana | 70808 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41902670 | Derived | Suryadevara HNSK, Hebert RC, Staszkiewicz J, Ravussin E, Marlatt KL, Singh P, Ghosh S. Transcriptional remodeling of human skeletal muscle following sleep restriction in postmenopausal women. Physiol Genomics. 2026 May 1;58(5):225-238. doi: 10.1152/physiolgenomics.00269.2025. Epub 2026 Mar 28. | |
| 36998155 | Derived |
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| ID | Term |
|---|---|
| D020447 | Parasomnias |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
| D006946 | Hyperinsulinism |
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| Habitual Sleep |
| Behavioral |
Women will be undergo 4 nights of habitual sleep. |
|
| Insulin-dependent suppression of lipolysis (via ex vivo adipose tissue biopsy analyses) |
Release of free fatty acids and glycerol in culture. |
| 4 days |
| Fat oxidation and substrate switching (via ex vivo skeletal muscle biopsy analyses) | Using primary myotubes, fat oxidation and substrate switching will be tested by measuring [1-14C]palmitate oxidation ± varying levels of glucose and pyruvate | 4 days |
| Insulin sensitivity (via ex vivo skeletal muscle biopsy analyses) | Myotubes will be incubated ± insulin (100nM) in media containing: [U-14C]-glucose to measure glucose oxidation and glycogen synthesis; [3H]-2-deoxyglucose to assess glucose uptake; or unlabeled DMEM to test insulin signaling (western blot) | 4 days |
| Gene expression (via ex vivo skeletal muscle biopsy analyses with RNASeq and RT-PCR) | Genes related to oxphos and circadian clock regulators will be assessed by RNASeq and confirmed with RT-PCR. | 4 days |
| Glucose Area-Under-The-Curve (via 2-hour standard meal test) | Glucose area-under-the-curve (AUC) will be calculated throughout a 2-hour period following consumption of a standard meal (dinner shake) test on Day 4 of each sleep condition. | 4 days |
| Insulin Area-Under-The-Curve (via 2-hour standard meal test) | Insulin area-under-the-curve (AUC) will be calculated throughout a 2-hour period following consumption of a standard meal (dinner shake) test on Day 4 of each sleep condition. | 4 days |
| Blood pressure (via 24-hour ambulatory blood pressure monitoring) | Blood pressure monitoring will be performed for a 24-hour period during Day 3 of each sleep conditions. | 24 hours |
| Resting metabolic rate (via indirect calorimetry) | O2 consumption and CO2 production will be measured by indirect calorimetry for 40 min (last 30 min will be used for calculations) using a metabolic cart. Resting metabolic rate will be derived using standard equations. | 4 days |
| Singh P, Beyl RA, Stephens JM, Noland RC, Richard AJ, Boudreau A, Hebert RC, Ravussin E, Broussard JL, St-Onge MP, Marlatt KL. Effect of sleep restriction on insulin sensitivity and energy metabolism in postmenopausal women: A randomized crossover trial. Obesity (Silver Spring). 2023 May;31(5):1204-1215. doi: 10.1002/oby.23739. Epub 2023 Mar 30. |
| D044882 |
| Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |