Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss

  1. Eve Van Cauter, PhD1
  1. 1Sleep, Metabolism and Health Center, Department of Medicine, University of Chicago, Chicago, IL, USA.
  2. 2Neuropsychology and Functional Neuroimaging Research Unit at the Center for Research in Cognition and Neurosciences and the ULB Neuroscience Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
  3. 3Department of Public Health and Caring Sciences; Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
  1. Address for correspondence: Rachel Leproult, Email: rleproult{at}


Shift workers, who are exposed to irregular sleep schedules resulting in sleep deprivation and misalignment of circadian rhythms, have an increased risk of diabetes relative to day workers. In healthy adults, sleep restriction without circadian misalignment promotes insulin resistance.

To determine whether the misalignment of circadian rhythms that typically occurs in shift work involves intrinsic adverse metabolic effects independently of sleep loss, twenty-six healthy adults were studied using a parallel group design. Both interventions involved 3 inpatient days with 10-h bedtimes followed by 8 inpatient days of sleep restriction to 5 hours, either with fixed nocturnal bedtimes (circadian alignment) or with bedtimes delayed by 8.5 hours on 4 of the 8 days (circadian misalignment). Daily total sleep time during the intervention was nearly identical in the aligned and misaligned conditions (4h48min[5min] vs. 4h45min[6min]). In both groups, insulin sensitivity significantly decreased after sleep restriction, without compensatory increase in insulin secretion, and inflammation increased. In male participants exposed to circadian misalignment, both the reduction in insulin sensitivity and the increase in inflammation doubled, compared to those who maintained regular nocturnal bedtimes.

Circadian misalignment as occurs in shift work may increase diabetes risk and inflammation, independently of sleep loss.

  • Received October 8, 2013.
  • Accepted January 6, 2014.

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