Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study.

backgroundInsufficient sleep increases the risk for insulin resistance, type 2 diabetes, and obesity, suggesting that sleep restriction may impair peripheral metabolic pathways. Yet, a direct link between sleep restriction and alterations in molecular metabolic pathways in any peripheral human tissue has not been shown.

objectiveTo determine whether sleep restriction results in reduced insulin sensitivity in subcutaneous fat, a peripheral tissue that plays a pivotal role in energy metabolism and balance.

designRandomized, 2-period, 2-condition, crossover clinical study.

settingUniversity of Chicago Clinical Resource Center.

participantsSeven healthy adults (1 woman, 6 men) with a mean age of 23.7 years (SD, 3.8) and mean body mass index of 22.8 kg/m(2) (SD, 1.6).

interventionFour days of 4.5 hours in bed or 8.5 hours in bed under controlled conditions of caloric intake and physical activity. MEASUREMENTS: Adipocytes collected from subcutaneous fat biopsy samples after normal and restricted sleep conditions were exposed to incremental insulin concentrations. The ability of insulin to increase levels of phosphorylated Akt (pAkt), a crucial step in the insulin-signaling pathway, was assessed. Total Akt (tAkt) served as a loading control. The insulin concentration for the half-maximal stimulation of the pAkt-tAkt ratio was used as a measure of cellular insulin sensitivity. Total body insulin sensitivity was assessed using a frequently sampled intravenous glucose tolerance test.

resultsThe insulin concentration for the half-maximal pAkt-tAkt response was nearly 3-fold higher (mean, 0.71 nM [SD, 0.27] vs. 0.24 nM [SD, 0.24]; P = 0.01; mean difference, 0.47 nM [SD, 0.33]; P = 0.01), and the total area under the receiver-operating characteristic curve of the pAkt-tAkt response was 30% lower (P = 0.01) during sleep restriction than during normal sleep. A reduction in total body insulin sensitivity (P = 0.02) paralleled this impaired cellular insulin sensitivity. LIMITATION: This was a single-center study with a small sample size.

conclusionSleep restriction results in an insulin-resistant state in human adipocytes. Sleep may be an important regulator of energy metabolism in peripheral tissues. PRIMARY FUNDING SOURCE: National Institutes of Health.