Diurnal Variation of Hormonal and Lipid Biomarkers in a Molecular Epidemiology-Like Setting

Abstract

IntroductionMany molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, investigate metabolic and hormonal markers. In general, sampling for these markers can occur at any time-point during the day or after an overnight fast. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system. When diurnal variation is larger than the inter-individual variation, time of day should be taken into account. Importantly, heterogeneity in diurnal variation and disturbance of circadian rhythms among a study population might increasingly occur as a result of our increasing 24/7 economy and related variation in exposure to environmental factors (such as light and food).AimThe aim of the present study was to determine whether a set of often used biomarkers shows diurnal variation in a setting resembling large molecular epidemiology studies, i.e., non-fasted and limited control possibilities for other environmental influences.ResultsWe show that markers for which diurnal variation is not an issue are adrenocorticotropic hormone, follicle stimulating hormone, estradiol and high-density lipoprotein. For all other tested markers diurnal variation was observed in at least one gender (cholesterol, cortisol, dehydroepiandrosterone sulfate, free fatty acids, low-density lipoprotein, luteinizing hormone, prolactin, progesterone, testosterone, triglycerides, total triiodothyronine and thyroid-stimulating hormone) or could not reliably be detected (human growth hormone).DiscussionThus, studies investigating these markers should take diurnal variation into account, for which we provide some options. Furthermore, our study indicates the need for investigating diurnal variation (in literature or experimentally) before setting up studies measuring markers in routine and controlled settings, especially since time-of-day likely matters for many more markers than the ones investigated in the present study.

Circadian rhythm influences induction of trained immunity by BCG vaccination

“…There are 2 main mechanisms that could explain the differential induction of trained immunity by morning or evening BCG vaccination: (i) changes in circulating modulators of immune responses, and (ii) cell-intrinsic circadian changes. The most obvious candidate for circulating modulators affected by circadian rhythm are corticosteroid hormones (35). As expected, circulating cortisol levels were significantly higher in the early morning 68) and late morning-vaccinated group (11 am to 12 pm, n = 66) for S. aureus-induced IL-1β and TNF-α, and between 8-9 am and 10-11 am (n = 8) subgroups for S. aureus-induced IL-6 two weeks after vaccination in favor of the early morning-vaccinated group (Figure 4, B-D).…”

Direct effects of the light environment on daily neuroendocrine control

“…In line with the circuit complexity highlighted above, the timing and diurnal pattern of prolactin secretion seems to exhibit significant flexibility according to species, sex, reproductive status, environmental conditions and so forth (Sinha et al 1975, Dubey et al 1983, Meier & Cincotta 1996, Cano et al 2008, Claustrat et al 2008, Roelfsema & Pijl 2012, Rietema et al 2015, van Kerkhof et al 2015. Nonetheless, the studies listed above (which include data from sheep, monkeys, humans and male nocturnal rodents) typically reveal higher levels of circulating prolactin during the night.…”

“…As with prolactin, diurnal patterns of TSH appear to vary depending on sex, species and/or gender studied. However, nocturnal rodents typically display elevated TSH during the early-mid day (Fukuda et al 1975, Rookh et al 1979, Wong et al 1983, while in humans TSH levels are elevated in the early-mid night (Hirschfeld et al 1996, Leproult et al 1997, van Kerkhof et al 2015. In rats, SCN lesions result in significant changes in the diurnal pattern of circulating TSH and thyroid hormone (Abe et al 1979, Kalsbeek et al 2000a, confirming a role for the central clock in regulating these.…”

Serum Progesterone Levels in Pregnant Women with Obstructive Sleep Apnea: A Case Control Study

“…While progesterone levels have not appeared to follow consistent circadian patterns, levels may fluctuate with pulsatile secretion and decrease after meals. [32][33][34] Lastly, our data are complicated by the fact that meaningful data on continuous airway pressure therapy use, duration, or compliance could not be reliably ascertained by a review of the obstetrical medical record among our subjects due to poor documentation, prohibiting any useful analysis of the effect of therapy on the described association. However, in this study, CPAP prescription among OSA cases may have perhaps led to a reduction in effect size and ultimately an underestimation of study results.…”