Circadian Misalignment Augments Markers of Insulin Resistance and Inflammation, Independently of Sleep Loss

TLDR

Shift workers experience irregular sleep schedules that cause circadian misalignment and sleep deprivation, increasing diabetes risk, and even sleep restriction alone is known to induce insulin resistance. The study investigates whether circadian misalignment independently worsens insulin sensitivity and inflammation beyond the effects of sleep loss. Twenty‑six healthy adults were randomized to either a circadian‑aligned or circadian‑misaligned sleep‑restriction protocol, each involving 3 days of 10‑hour bedtimes followed by 8 days of 5‑hour sleep with either fixed nocturnal bedtimes or 8.5‑hour delayed bedtimes on four days. While total sleep time was similar, circadian misalignment doubled the decline in insulin sensitivity and the rise in inflammation compared with alignment, indicating that misalignment independently elevates diabetes risk and inflammation.

Abstract

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, a parallel group design was used to study 26 healthy adults. Both interventions involved 3 inpatient days with 10-h bedtimes, followed by 8 inpatient days of sleep restriction to 5 h with fixed nocturnal bedtimes (circadian alignment) or with bedtimes delayed by 8.5 h on 4 of the 8 days (circadian misalignment). Daily total sleep time (SD) during the intervention was nearly identical in the aligned and misaligned conditions (4 h 48 min [5 min] vs. 4 h 45 min [6 min]). In both groups, insulin sensitivity (SI) significantly decreased after sleep restriction, without a compensatory increase in insulin secretion, and inflammation increased. In male participants exposed to circadian misalignment, the reduction in SI and the increase in inflammation both doubled compared with those who maintained regular nocturnal bedtimes. Circadian misalignment that occurs in shift work may increase diabetes risk and inflammation, independently of sleep loss.