Chronic Insufficient Sleep in Women Impairs Insulin Sensitivity Independent of Adiposity Changes: Results of a Randomized Trial.

OBJECTIVE: Insufficient sleep is associated with type 2 diabetes, yet the causal impact of chronic insufficient sleep on glucose metabolism in women is unknown. We investigated whether prolonged mild sleep restriction (SR), resembling real-world short sleep, impairs glucose metabolism in women. RESEARCH DESIGN AND METHODS: Women (aged 20-75 years) without cardiometabolic diseases and with actigraphy-confirmed habitual total sleep time (TST) of 7-9 h/night were recruited to participate in this randomized, crossover study with two 6-week phases: maintenance of adequate sleep (AS) and 1.5 h/night SR. Outcomes included plasma glucose and insulin levels, HOMA of insulin resistance (HOMA-IR) values based on fasting blood samples, as well as total area under the curve for glucose and insulin, the Matsuda index, and the disposition index from an oral glucose tolerance test. RESULTS: Our sample included 38 women (n = 11 postmenopausal women). Values are reported with ±SEM. Linear models adjusted for baseline outcome values demonstrated that TST was reduced by 1.34 ± 0.04 h/night with SR versus AS (P < 0.0001). Fasting insulin (ß = 6.8 ± 2.8 pmol/L; P = 0.016) and HOMA-IR (ß = 0.30 ± 0.12; P = 0.016) values were increased with SR versus AS, with effects on HOMA-IR more pronounced in postmenopausal women compared with premenopausal women (ß = 0.45 ± 0.25 vs. ß = 0.27 ± 0.13, respectively; P for interaction = 0.042). Change in adiposity did not mediate the effects of SR on glucose metabolism or change results in the full sample when included as a covariate. CONCLUSIONS: Curtailing sleep duration to 6.2 h/night, reflecting the median sleep duration of U.S. adults with short sleep, for 6 weeks impairs insulin sensitivity, independent of adiposity. Findings highlight insufficient sleep as a modifiable risk factor for insulin resistance in women to be targeted in diabetes prevention efforts.

Paradoxical Effects of Prolonged Insufficient Sleep on Lipid Profile: A Pooled Analysis of 2 Randomized Trials.

Background Insufficient sleep is associated with increased cardiovascular disease risk, but causality is unclear. We investigated the impact of prolonged mild sleep restriction (SR) on lipid and inflammatory profiles. Methods and Results Seventy-eight participants (56 women [12 postmenopausal]; age, 34.3±12.5 years; body mass index, 25.8±3.5 kg/m2) with habitual sleep duration 7 to 9 h/night (adequate sleep [AS]) underwent two 6-week conditions in a randomized crossover design: AS versus SR (AS-1.5 h/night). Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and inflammatory markers (CRP [C-reactive protein], interleukin 6, and tumor necrosis factor-α) were assessed. Linear models tested effects of SR on outcomes in the full sample and by sex+menopausal status (premenopausal versus postmenopausal women+men). In the full sample, SR increased high-density lipoprotein cholesterol compared with AS (ß=1.2±0.5 mg/dL; P=0.03). Sex+menopausal status influenced the effects of SR on change in total cholesterol (P-interaction=0.04), LDL-C (P-interaction=0.03), and interleukin 6 (P-interaction=0.07). Total cholesterol and LDL-C decreased in SR versus AS in premenopausal women (total cholesterol: ß=-4.2±1.9 mg/dL; P=0.03; LDL-C: ß=-6.3±2.0 mg/dL; P=0.002). Given paradoxical effects of SR on cholesterol concentrations, we explored associations between changes in inflammation and end point lipids under each condition. Increases in interleukin 6 and tumor necrosis factor-α during SR tended to relate to lower LDL-C in premenopausal women (interleukin 6: ß=-5.3±2.6 mg/dL; P=0.051; tumor necrosis factor-α: ß=-32.8±14.2 mg/dL; P=0.027). Conclusions Among healthy adults, prolonged insufficient sleep does not increase atherogenic lipids. However, increased inflammation in SR tends to predict lower LDL-C in premenopausal women, resembling the "lipid paradox" in which low cholesterol associates with increased cardiovascular disease risk in proinflammatory conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02835261, NCT02960776.