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 (T2D), 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 (20-75 y) 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-wk phases: maintenance of adequate sleep (AS) and 1.5 h/night SR. Outcomes included plasma glucose, insulin, HOMA-IR from fasting blood draws as well as total area under the curve (AUC) for glucose and insulin, Matsuda index, and disposition index from an oral glucose tolerance test. Results: Our sample included 38 women (11 postmenopausal). Linear models adjusted for baseline outcome values demonstrated that TST was reduced by 1.34±0.04 h/night in SR vs. AS (p<0.0001). Fasting insulin (b=6.8±2.8 pmol/L, p=0.016) and HOMA-IR (b=0.30±0.12, p=0.016) were increased in SR vs. AS, with effects on HOMA-IR more pronounced in postmenopausal vs. premenopausal women (b=0.45±0.25 vs. b=0.27±0.13, p-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 US adults with short sleep, for 6 wk 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.