Effect of Sleep Restriction on Adipose Tissue and Skeletal Muscle Insulin Sensitivity

Not Applicable

Completed

• Conditions: Sleep Disturbance; Insulin Sensitivity; Cardiovascular Risk Factor; Postmenopausal Symptoms
• Interventions: Behavioral: Habitual Sleep; Behavioral: Sleep Restriction

• Registration Number: NCT04286451
• Lead Sponsor: Pennington Biomedical Research Center

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-01-13
• Study First Submitted QC: 2020-02-24
• Study First Posted: 2020-02-27
• Study Start: 2020-07-28
• Primary Completion: 2022-04-13
• Study Completion: 2022-04-13
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-11
• Last Update Posted: 2022-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 14

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Habitual Sleep	Habitual Sleep	Women will undergo 4 nights of habitual sleep treatment.
Sleep Restriction	Sleep Restriction	Women will undergo 4 nights of sleep restriction treatment.

Primary Outcome Measures

Name	Time	Method
Glucose infusion rate (via 2-step hyperinsulinemic-euglycemic clamp) (in vivo)	4 days	Insulin sensitivity by a 2-step hyperinsulinemic euglycemic clamp is performed at the end sleep conditions.

Secondary Outcome Measures

Name	Time	Method
Adipose tissue insulin sensitivity (via free fatty acid area-under-the-curve during the low-dose clamp) (in vivo)	4 days	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.
Insulin-dependent suppression of lipolysis (via ex vivo adipose tissue biopsy analyses)	4 days	Release of free fatty acids and glycerol in culture.
Gene expression (via ex vivo skeletal muscle biopsy analyses with RNASeq and RT-PCR)	4 days	Genes related to oxphos and circadian clock regulators will be assessed by RNASeq and confirmed with RT-PCR.
Insulin Area-Under-The-Curve (via 2-hour standard meal test)	4 days	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.
Blood pressure (via 24-hour ambulatory blood pressure monitoring)	24 hours	Blood pressure monitoring will be performed for a 24-hour period during Day 3 of each sleep conditions.
Glucose Area-Under-The-Curve (via 2-hour standard meal test)	4 days	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.
Resting metabolic rate (via indirect calorimetry)	4 days	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.
Fat oxidation and substrate switching (via ex vivo skeletal muscle biopsy analyses)	4 days	Using primary myotubes, fat oxidation and substrate switching will be tested by measuring \[1-14C\]palmitate oxidation ± varying levels of glucose and pyruvate
Insulin sensitivity (via ex vivo skeletal muscle biopsy analyses)	4 days	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)

Trial Locations

Locations (1)

Pennington Biomedical Research Center; 🇺🇸 Baton Rouge, Louisiana, United States