Unanticipated daytime melatonin secretion on a simulated night shift schedule generates a distinctive 24‐h melatonin rhythm with antiphasic daytime and nighttime peaks

Abstract

The daily rhythm of plasma melatonin concentrations is typically unimodal, with one broad peak during the circadian night and near‐undetectable levels during the circadian day. Light at night acutely suppresses melatonin secretion and phase shifts its endogenous circadian rhythm. In contrast, exposure to darkness during the circadian day has not generally been reported to increase circulating melatonin concentrations acutely. Here, in a highly‐controlled simulated night shift protocol with 12‐h inverted behavioral/environmental cycles, we unexpectedly found that circulating melatonin levels were significantly increased during daytime sleep (p < .0001). This resulted in a secondary melatonin peak during the circadian day in addition to the primary peak during the circadian night, when sleep occurred during the circadian day following an overnight shift. This distinctive diurnal melatonin rhythm with antiphasic peaks could not be readily anticipated from the behavioral/environmental factors in the protocol (e.g., light exposure, posture, diet, activity) or from current mathematical model simulations of circadian pacemaker output. The observation, therefore, challenges our current understanding of underlying physiological mechanisms that regulate melatonin secretion. Interestingly, the increase in melatonin concentration observed during daytime sleep was positively correlated with the change in timing of melatonin nighttime peak (p = .002), but not with the degree of light‐induced melatonin suppression during nighttime wakefulness (p = .92). Both the increase in daytime melatonin concentrations and the change in the timing of the nighttime peak became larger after repeated exposure to simulated night shifts (p = .002 and p = .006, respectively). Furthermore, we found that melatonin secretion during daytime sleep was positively associated with an increase in 24‐h glucose and insulin levels during the night shift protocol (p = .014 and p = .027, respectively). Future studies are needed to elucidate the key factor(s) driving the unexpected daytime melatonin secretion and the melatonin rhythm with antiphasic peaks during shifted sleep/wake schedules, the underlying mechanisms of their relationship with glucose metabolism, and the relevance for diabetes risk among shift workers.

Circadian desynchrony and glucose metabolism

“…Interestingly, in the same randomized cross‐over trial, individuals with a MTNR1B diabetes risk variant exhibited a stronger degree of impaired glucose tolerance after late eating at night 203 . Low nocturnal melatonin levels have also been associated with impaired glucose tolerance and insulin resistance 204,205 and an increased risk of type 2 diabetes, 206 while high melatonin levels during daytime sleep in shift workers were associated with impaired glucose tolerance 207 . In a cross‐sectional study in adolescents with obesity, a low nocturnal melatonin concentration was associated with insulin resistance 208 .…”

“…203 Low nocturnal melatonin levels have also been associated with impaired glucose tolerance and insulin resistance 204,205 and an increased risk of type 2 diabetes, 206 while high melatonin levels during daytime sleep in shift workers were associated with impaired glucose tolerance. 207 In a cross-sectional study in adolescents with obesity, a low nocturnal melatonin concentration was associated with insulin resistance. 208 In addition, a shorter interval between dim-light melatonin onset and sleep onset has been associated with higher fasting insulin and HOMA-IR.…”

The role of melatonin in the development of postmenopausal osteoporosis

“…Its secretion increases with weak light stimulation at night but decreases in the daytime (Carstensen et al, 2022). The rhythmic regulation of melatonin affected the metabolism of nutrients, including carbohydrates, lipids and proteins, indicating the important role of melatonin in maintaining body functions (Kent et al, 2022;Qian et al, 2022). A previous clinical study demonstrated the protective effect of melatonin in rhythmic secretion on bone metabolism in postmenopausal women (Ostrowska et al, 2001b).…”

The Role of Melatonin in Chronic Kidney Disease and Its Associated Risk Factors: A New Tool in Our Arsenal?

“…Night work is a special category that should be mentioned. Such individuals could be at increased risk because an additional MT peak is prevalent during daytime sleep, complementary to the anticipated peak at the circadian night, leading to higher 24-h glucose levels [51]. This may partially explain the increased incidence of T2DM in female nurses who work on night shifts [52].…”