Subchronic sleep restriction causes tissue-specific insulin resistance.

Area of Science:

• Metabolic Physiology
• Endocrinology
• Sleep Medicine

Background:

• Short sleep duration is a known risk factor for type 2 diabetes.
• Subchronic sleep restriction (SR) induces insulin resistance, but underlying tissue-specific mechanisms remain unclear.

Purpose of the Study:

• To investigate the impact of subchronic sleep restriction on hepatic and peripheral insulin sensitivity.
• To assess alterations in substrate utilization and stress hormone levels following sleep restriction.

Main Methods:

• Randomized crossover study involving 14 participants with 5 nights of sleep restriction (4 hours time in bed) or normal sleep (8 hours time in bed).
• Insulin sensitivity assessed via hyperinsulinemic-euglycemic clamp and hepatic insulin sensitivity using stable isotope techniques.
• Measurements included stress hormones (cortisol, metanephrine, normetanephrine), nonesterified fatty acids (NEFA), β-hydroxybutyrate (β-OH butyrate), resting energy expenditure (REE), and respiratory quotient (RQ).

Main Results:

• Whole-body insulin sensitivity decreased by 25% and peripheral insulin sensitivity by 29% with SR (P < .01).
• Hepatic insulin sensitivity remained unchanged, but gluconeogenesis increased (P = .03).
• Fasting NEFA and β-OH butyrate levels rose significantly (62% and 55%), while RQ decreased (P = .045). Stress hormones showed modest increases.

Conclusions:

• Subchronic sleep restriction induces peripheral insulin resistance, increased lipolysis (elevated NEFA), and enhanced fat oxidation (decreased RQ, increased β-OH butyrate).
• Elevated NEFA levels may drive peripheral insulin resistance and hepatic metabolic changes.
• Increased cortisol and metanephrine may contribute to insulin resistance by promoting lipolysis.