Artificial lighting at night (ALAN) leads to pervasive light pollution, affecting ecosystems and human health globally. Satellite assessments reveal widespread nocturnal illumination worldwide and research indicates adverse health effects. Environmental light pollution disrupts natural cycles, affecting the behavior and reproduction of various organisms.

In this narrative review we aimed to present research on the effects of ALAN on glucose metabolism and diabetes and hone on its recently reported association with gestational diabetes (GDM).

Conflicting data exist on the effects of melatonin's administration vis-à-vis glycemia, with some studies suggesting beneficial outcomes for patients with type 2 diabetes mellitus and insomnia. Ambient light influences plasma glucose, with bright light increasing both fasting and postprandial glucose levels. Perinatal light exposure is linked to later-life health risks and prenatal exposure to ALAN is linked to fetal macrosomia. Analyzing European ALAN data in conjunction with epidemiological records for GDM reveals a notable probable association. Additionally, recent research from China (one case-control and two cohort studies) has shown that exposure to ALAN during pregnancy significantly increases the risk of GDM.

Despite progress, interdisciplinary research is needed to understand the impact of light pollution on health, especially regarding disrupted light-dark cycles and physiological functions relevant to conditions like GDM. At present, the simplest advice for all people and particularly for women who anticipate pregnancy, or for pregnant women, is to ensure a totally dark environment during sleep time.

Current studies have presented conflicting findings regarding the associations between light at night (LAN) exposure and the risk of overweight/obesity, hypertension, and diabetes. Our study systematically summarized the evidence of the association between LAN exposure and the risk of overweight/obesity, hypertension, and diabetes. We searched five databases (PubMed, Web of Science, Embase, Scopus, and Cochrane) for observational studies published up to 1 August 2023. The pooled odds ratio (ORs) and 95% confidence intervals (CIs) were estimated by random-effects models for the association. Eighteen studies were included in the meta-analysis. Compared with the group with the lowest level of LAN, the group with the highest level of LAN is associated with an increased risk of overweight/obesity (pooled OR = 1.19, 95%CI: 1.13-1.26), hypertension (pooled OR: 1.86, 95% CI:1.28-2.72), and diabetes (pooled OR = 1.21, 95%CI: 1.07-1.31). Our meta-analysis demonstrated LAN exposure is associated with increased risk of overweight/obesity, hypertension, and diabetes.

According to the IDF Diabetes Atlas regularly published by International Diabetes Federation, the prevalence of diabetes and impaired glucose tolerance (IGT), diabetes-related mortality and health expenditure are becoming serious eventually at the global, regional and national level. While the data alarm people, the exact cause remains unknown. It is widely accepted that glucose metabolism can be impaired by circadian rhythms disruption and sleep disturbances, both closely linked to exposure to light at night. However, there is little direct experiment on primates to study the precise extent of how serious bright sleeping environment at night impairs glucose metabolism, what the relationship is between nocturnal brightness and the development of diabetes and IGT, any difference between male and female, and whether aging and weight are involved. This study aims to address these questions in monkeys.

In a reduced daytime bright condition resembling human living rooms, 197 Cynomolgus (130 male, 67 female) were exposed to three distinct light intensities (13, 35, 75Lux) at night for consecutive ten months. Animals were retrospectively divided into four groups according to glucose metabolic status by the end of the experimental session, spontaneous diabetes mellitus (SDM, N=11), light-induced diabetes (LID, N=83), impaired fasting glucose tolerance (IFG, N=36), and normal glucose tolerance (NGT, N=67). Data pertaining to the glucose metabolism such as concentrations of fasting glucose, glycosylated hemoglobin, plasma insulin and C-peptide were collected monthly and analyzed.

1) Bright night exasperated glucose metabolism in individuals with pre-existing diabetes, led to premature death; 2) Stronger white light intensity-dependently induced diabetes and IFG in previous healthy monkeys: the brighter the light, the quicker the metabolism disturbance and IFG developed, and also the higher morbidity of LID and IFG; 3) Exposure to nocturnal light had a synergistic impairing effect on glucose metabolism with aging and weight. 4) Female were more susceptible to night brightness.

Light in sleeping environment exacerbates glucose metabolism in individuals with pre-existing diabetes, leads to IFG and diabetes in healthy primates. Moreover, the harmful effects of bright night on glucose metabolism are synergistic with aging and weight.

The demarcation between monogenic and polygenic type 2 diabetes (T2D) is less distinct than previously believed. Notably, recent research has highlighted a new entity, that we suggest calling oligogenic forms of T2D, serving as a genetic link between these two forms. In this opinion article, we have reviewed scientific advances that suggest categorizing genes involved in oligogenic T2D. Research focused on polygenic T2D has faced challenges in deepening our comprehension of the pathophysiology of T2D due to the inability to directly establish causal links between a signal and the molecular mechanisms underlying the disease. However, the study of oligogenic forms of T2D has illuminated distinct causal connections between genes and disease risk, thereby indicating potential new drug targets.

Over the past decades, the global prevalence of Type 2 diabetes mellitus (T2D) and impaired glucose tolerance (IGT) has been increasing at an epidemic rate, yet the exact cause remains unknown. It is widely accepted that glucose metabolism can be impaired by circadian rhythms and sleep disturbances. Concurrently, exposures to light at night have been closely linked to circadian and sleep disturbances. However, there is no direct experiment on primates to demonstrate the precise extent of how serious light pollution impairs glucose metabolism, whether people will eventually become accustomed to this environment, and whether the pollution has synergistic impairing effects with aging and weight on glucose metabolism. To quantitatively address these questions, 137 cynomolgus were exposed to three distinct nocturnal light intensities for consecutive 10 months. Monthly glucose metabolism assessments were conducted. Data pertaining to the mortality rate of preexisting diabetes, incidence of light-induced diabetes and IGT, and alterations in insulin secretion were collected and analyzed. The results show that nocturnal light (1) caused premature deaths in individuals with preexisting diabetes; (2) intensity-dependently induced diabetes and IGT in previous healthy monkeys; (3) intensity-dependently reduced melatonin secretion; (4) had a synergistic impairing effect on glucose metabolism with aging and weight; and (5) although monkeys would eventually adapt to the environment, the disrupted glucose metabolism would not fully recover in most individuals. In conclusion, nocturnal light is associated with the global high prevalence of T2D and IGT. The harmful effects of light pollution on glucose metabolism are synergistic with age and weight.

The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE2), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE2 inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE2 inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE2 inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE2 inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors.

Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies.

The relationships between the feeding rhythm, sleep and cognition in Alzheimer's disease (AD) are incompletely understood, but meal time could provide an easy-to-implement method of curtailing disease-associated disruptions in sleep and cognition. Furthermore, known sex differences in AD incidence could relate to sex differences in circadian rhythm/sleep/cognition interactions.

The 5xFAD transgenic mouse model of AD and non-transgenic wild-type controls were studied. Both female and male mice were used. Food access was restricted each day to either the 12-h light phase (light-fed groups) or the 12-h dark phase (dark-fed groups). Sleep (electroencephalographic/electromyographic) recording and cognitive behavior measures were collected.

The 5xFAD genotype reduces NREM and REM as well as the number of sleep spindles. In wild-type mice, light-fed groups had disrupted vigilance state amounts, characteristics, and rhythms relative to dark-fed groups. These feeding time differences were reduced in 5xFAD mice. Sex modulates these effects. 5xFAD mice display poorer spatial memory that, in female mice, is curtailed by dark phase feeding. Similarly, female 5xFAD mice have decreased anxiety-associated behavior. These emotional and cognitive measures are correlated with REM amount.

Our study demonstrates that the timing of feeding can alter many aspects of wake, NREM and REM. Unexpectedly, 5xFAD mice are less sensitive to these feeding time effects. 5xFAD mice demonstrate deficits in cognition which are correlated with REM, suggesting that this circadian-timed aspect of sleep may link feeding time and cognition. Sex plays an important role in regulating the impact of feeding time on sleep and cognition in both wild-type and 5xFAD mice, with females showing a greater cognitive response to feeding time than males.

Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes.

To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes.

The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model.

The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN.

Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank.

Two-hour, 7-sample OGTT.

Fasting, nadir, and integrated glucagon concentrations.

One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype.

The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.

The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin secretion, and photoperiod regulates melatonin levels by promoting its production and secretion at night in response to darkness. This hormone is becoming more and more understood for its functions as an immune-modulatory, anti-inflammatory, and antioxidant hormone. Melatonin may have a major effect on several diabetes-related disturbances, such as hormonal imbalances, oxidative stress, sleep disturbances, and mood disorders, according to recent research. This has raised interest in investigating the possible therapeutic advantages of melatonin in the treatment of diabetic complications. In addition, several studies have described that melatonin has been linked to the development of diabetes, cancer, Alzheimer's disease, immune system disorders, and heart diseases. In this review, we will highlight some of the functions of melatonin regarding vascular biology.

Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults.

In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work.

For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (pinteraction=0·013) among the female nurses.

With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work.

US National Institutes of Health.

The circadian timing system controls glucose metabolism in a time-of-day dependent manner. In mammals, the circadian timing system consists of the main central clock in the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks in peripheral tissues. The oscillations produced by these different clocks with a period of approximately 24-h are generated by the transcriptional-translational feedback loops of a set of core clock genes. Glucose homeostasis is one of the daily rhythms controlled by this circadian timing system. The central pacemaker in the SCN controls glucose homeostasis through its neural projections to hypothalamic hubs that are in control of feeding behavior and energy metabolism. Using hormones such as adrenal glucocorticoids and melatonin and the autonomic nervous system, the SCN modulates critical processes such as glucose production and insulin sensitivity. Peripheral clocks in tissues, such as the liver, muscle, and adipose tissue serve to enhance and sustain these SCN signals. In the optimal situation all these clocks are synchronized and aligned with behavior and the environmental light/dark cycle. A negative impact on glucose metabolism becomes apparent when the internal timing system becomes disturbed, also known as circadian desynchrony or circadian misalignment. Circadian desynchrony may occur at several levels, as the mistiming of light exposure or sleep will especially affect the central clock, whereas mistiming of food intake or physical activity will especially involve the peripheral clocks. In this review, we will summarize the literature investigating the impact of circadian desynchrony on glucose metabolism and how it may result in the development of insulin resistance. In addition, we will discuss potential strategies aimed at reinstating circadian synchrony to improve insulin sensitivity and contribute to the prevention of type 2 diabetes.

Melatonin is a neurohormone synthesized from dietary tryptophan in various organs, including the pineal gland and the retina. In the pineal gland, melatonin is produced at night under the control of the master clock located in the suprachiasmatic nuclei of the hypothalamus. Under physiological conditions, the pineal gland seems to constitute the unique source of circulating melatonin. Melatonin is involved in cellular metabolism in different ways. First, the circadian rhythm of melatonin helps the maintenance of proper internal timing, the disruption of which has deleterious effects on metabolic health. Second, melatonin modulates lipid metabolism, notably through diminished lipogenesis, and it has an antidiabetic effect, at least in several animal models. Third, pharmacological doses of melatonin have antioxidative, free radical-scavenging, and anti-inflammatory properties in various in vitro cellular models. As a result, melatonin can be considered both a circadian time-giver and a homeostatic monitor of cellular metabolism, via multiple mechanisms of action that are not all fully characterized. Aging, circadian disruption, and artificial light at night are conditions combining increased metabolic risks with diminished circulating levels of melatonin. Accordingly, melatonin supplementation could be of potential therapeutic value in the treatment or prevention of metabolic disorders. More clinical trials in controlled conditions are needed, notably taking greater account of circadian rhythmicity.

Diabetic retinopathy (DR) is one of the most prevalent microvascular diabetic complications. Poor sleep health and obstructive sleep apnea (OSA) are risk factors for diabetes and poor glycemic control. Recent studies have suggested associations between poor sleep health/OSA and DR. Furthermore, there have been suggestions of melatonin dysregulation in the context of DR. We conducted a systematic review and meta-analysis exploring the associations between multidimensional sleep health (duration, satisfaction, efficiency, timing/regularity and alertness), OSA and melatonin with DR. Forty-two studies were included. Long, but not short sleep, was significantly associated with DR, OR 1.41 (95%CI 1.21, 1.64). Poor sleep satisfaction was also significantly associated with DR, OR 2.04 (1.41, 2.94). Sleep efficiency and alertness were not associated with DR, while the evidence on timing/regularity was scant. Having OSA was significantly associated with having DR, OR 1.34 (1.07, 1.69). Further, those with DR had significantly lower melatonin/melatonin metabolite levels than those without DR, standardized mean difference -0.94 (-1.44, -0.44). We explored whether treating OSA with continuous positive airway pressure (CPAP) led to improvement in DR (five studies). The results were mixed among studies, but potential benefits were observed in some. This review highlights the association between poor multidimensional sleep health and DR.

This systematic review of 52 studies provides a quantitative synthesis of the empirical literature on social and circadian rhythm correlates of suicidal thoughts and behaviors (STB). Small-to-medium pooled effect sizes were observed for associations between evening chronotype and STB and suicidal ideation (SI), although the pooled effect size diminished when accounting for publication bias. Three studies employed longitudinal designs and suggested eveningness was predictive of future STB, with a small-to-medium effect size. Social rhythm irregularity was also a significant correlate of STB with pooled effect sizes in the medium range. Overall circadian rhythm disruption was not associated with STB, although certain circadian rhythm metrics, including mean daytime activity, circadian rhythm sleep-wake disorder diagnosis, and actigraphy-assessed amplitude were associated with STB. Pooled effect sizes for these indices were in the medium to large range. There is a need for additional longitudinal research on actigraphy-based circadian parameters and objective markers of circadian phase (i.e., dim-light melatonin onset) to gain a clearer understanding of associations of endogenous circadian function and STB beyond that which can be captured via self-report.

To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.

We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables. We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from zero. In addition, the leave-one-out method was used for sensitivity analysis to verify the stability and reliability of the results.

We selected 248 SNPs independently associated with insomnia at the genome-wide level (P<5×10-8) as a preliminary candidate set of instrumental variables. After clumping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs, a total of 167 SNPs associated with insomnia were included as final instrumental variables. The F statistic of this study was 39. 74, which was in line with the relevance assumption of Mendelian randomization. IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1. 14 times more likely to develop type 2 diabetes mellitus than those without insomnia (95% CI: 1.09-1.21, P<0.001). The weighted median estimator (WME) method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus. And MR-Egger regression also showed that the effect was less likely to be triggered by pleiotropy. Sensitivity analyses produced directionally similar estimates.

Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

Low levels of 6-sulfatoxymelatonin, the primary urinary metabolite of melatonin, have been linked to cancer and cardiometabolic outcomes in White and female populations.

We examined the association between adulthood adiposity and 6-sulfatoxymelatonin levels in a racially and ethnically diverse population. Our study included 4,078 men in the Multiethnic Cohort with adiposity measurements at enrollment (1993-1996) and biomarkers measured in urines collected in 1995 and 2005. Multivariable linear regression models were used to estimate the percent change in 6-sulfatoxymelatonin levels and 95% confidence intervals (CI). Associations were examined separately by racial/ethnic group.

The prevalence of obesity varied by race and ethnicity, from 10% for Japanese American men to 34% for Native Hawaiian men. Compared with men with normal body mass index (BMI), men who were overweight (-7.8%; 95% CI, -11.9 to -3.5%) and obese (-18.1%; 95% CI, -23.2 to -12.6%) had significantly lower 6-sulfatoxymelatonin levels adjusting for potential confounding factors. Increasing weight gain in adulthood was also associated with lower 6-sulfatoxymelatonin (Ptrend < 0.0001). The inverse associations for BMI and weight change were qualitatively similar across racial and ethnic groups.

Obesity is inversely associated with melatonin in a racially diverse population. This finding is relevant given higher rates of obesity among Black, Native Hawaiian, and Latino men, as well as potential racial and ethnic differences in circadian function.

Melatonin may be a relevant biomarker among obesity-associated malignancies and could shed light on a potential mechanism of cancer disparities.

There are currently no effective treatments to prevent, halt, or reverse Alzheimer's disease (AD), the most common cause of dementia in older adults. Melatonin, a relatively harmless over-the-counter supplement, may offer some benefits to patients with AD. Melatonin is known for its sleep-enhancing properties, but research shows that it may provide other advantages as well, such as antioxidant and anti-amyloidogenic properties. Clinical trials for melatonin use in AD have mixed results but, overall, show modest benefits. However, it is difficult to interpret clinical research in this area as there is little standardization to guide the administration and study of melatonin. This review covers basic biology and clinical research on melatonin in AD focusing on prominent hypotheses of pathophysiology of neurodegeneration and cognitive decline in AD (i.e., amyloid and tau hypotheses, antioxidant and anti-inflammation, insulin resistance and glucose homeostasis, the cholinergic hypothesis, sleep regulation, and the hypothalamic-pituitary-adrenal axis and cortisol). This is followed by a discussion on pending clinical trials, considerations for future research protocols, and open questions in the field.

A new type of lighting using violet-excitation light-emitting diodes (LEDs) with an action spectrum centered at approximately 405 nm was developed. Although violet-excitation LEDs can reduce melatonin suppression compared with blue-excitation LEDs, no studies have compared the effects of violet-excitation LEDs with those of blue-excitation LEDs on melatonin suppression. This study was designed to compare the effects of violet-excitation LEDs with those of blue-excitation LEDs on melatonin suppression, psychomotor vigilance, and sleepiness.

Sixteen healthy Japanese males aged 20-39 years were exposed to violet- and blue-excitation LEDs for 3 hours in a crossover randomized manner. The primary outcome was changes in salivary melatonin levels compared with the baseline levels. The secondary outcomes were changes in psychomotor vigilance and the Karolinska Sleepiness Scale. Melatonin suppression was calculated from the difference in the area under the curves between the baseline and intervention.

Of the 16 participants, 15 completed the measurements. The baseline characteristics did not differ significantly between the 2 groups. After adjusting for age, a difference of 16.28 pg/mL in mean melatonin suppression was observed between the violet- and blue-excitation LED groups (-2.15 pg/mL vs -18.43 pg/mL; P = .006). The overall melatonin suppression by violet-excitation LEDs was 48.6% smaller than that by blue-excitation LEDs. No significant differences in psychomotor vigilance and sleepiness were observed between the 2 groups.

Melatonin suppression in healthy Japanese males exposed to violet-excitation LEDs was significantly smaller than that in those exposed to blue-excitation LEDs. Our preliminary findings indicate that violet-excitation LEDs may have the potential to reduce the magnitude of blue-excitation LED-induced melatonin suppression.

Mitsui K, Saeki K, Sun M, Yamagami Y, Tai Y, Obayashi K. Effects of a violet-excitation light-emitting diode on melatonin secretion and sleepiness: preliminary findings from a randomized controlled trial. J Clin Sleep Med. 2024;20(1):101-109.

Night shift work is associated with sleep disturbances, obesity, and cardiometabolic diseases. Disruption of the circadian clock system has been suggested to be an independent cause of type 2 diabetes and cardiovascular disease in shift workers. We aimed to improve alignment of circadian timing with social and environmental factors with administration of melatonin.

In a randomized, placebo-controlled, prospective study, we analysed the effects of 2 mg of sustained-release melatonin versus placebo on glucose tolerance, insulin resistance indices, sleep quality, circadian profiles of plasma melatonin and cortisol, and diurnal blood pressure profiles in 24 rotating night shift workers during 12 weeks of treatment, followed by 12 weeks of wash-out. In a novel design, the time of melatonin administration (at night or in the morning) depended upon the shift schedule. We also compared the baseline profiles of the night shift (NS) workers with 12 healthy non-night shift (NNS)-working controls.

We found significantly impaired indices of insulin resistance at baseline in NS versus NNS (p < 0.05), but no differences in oral glucose tolerance tests nor in the diurnal profiles of melatonin, cortisol, or blood pressure. Twelve weeks of melatonin treatment did not significantly improve insulin resistance, nor did it significantly affect diurnal blood pressure or melatonin and cortisol profiles. Melatonin administration, however, caused a significant improvement in sleep quality which was significantly impaired in NS versus NNS at baseline (p < 0.001).

Rotating night shift work causes mild-to-moderate impairment of sleep quality and insulin resistance. Melatonin treatment at bedtime improves sleep quality, but does not significantly affect insulin resistance in rotating night shift workers after 12 weeks of administration.

Diabetic nephropathy (DN) is a common complication of diabetes, and it is also the main cause of chronic renal failure. Physiological/pathological changes mediated by high glucose are the main factors causing injury of DN, including the enhancement of polyol pathway, the accumulation of advanced glycation products (AGEs), and the activation of protein kinase C (PKC) and transforming growth factor-β (TGF-β) signals. In addition, the abnormal activation of renin-angiotensin system (RAS) and oxidative stress are also involved. Melatonin is a physiological hormone mainly secreted by the pineal gland which has been proved to be related to diabetes. Studies have shown that exogenous melatonin intervention can reduce blood glucose and alleviate high glucose mediated pathological damage. At the same time, melatonin also has a strong antioxidant effect, and can inhibit the activation of RAS. Therefore, it is of great significance to explore the therapeutic effect and value of melatonin on DN.

Most studies have shown that a single item of self-reported sleep duration is related to mortality risk. However, the long-term effect of sleep duration on mortality remains unclear in patients with diabetes. This study aimed to examine the associations of 3-year trajectory patterns of sleep duration with all-cause and expanded cardiovascular disease mortality in patients with type 2 diabetes.

Patients with type 2 diabetes and self-reported sleep duration during a 3-year interval were included. Expanded cardiovascular disease was defined as death due to cardiovascular disease, diabetes, and kidney diseases. Cox's proportional hazards models were employed to examine the associations between sleep duration patterns and mortality after controlling for sociodemographic factors, lifestyle behaviors, diabetes-related variables, diabetic complications, and medication use.

A total of 7591 patients were included for analysis, and 995 deaths (13.11%) and 424 expanded cardiovascular disease deaths (5.59%) were observed during a mean follow-up of 8.51 years. Five trajectory patterns of sleep duration were identified: cluster 1: "constant 7- to 8-hour group" (50.03%); cluster 2: "constant low group" (19.68%); cluster 3: "high with decreasing trend group" (3.08%); cluster 4: "low with fluctuation group" (1.28%); and cluster 5: "constant high group" (25.93%). Compared with cluster 1, clusters 3 and 4 were associated with increased risks of all-cause mortality (1.41, 1.08-1.84; 1.44, 1.01-2.05), and cluster 5 was associated with high risks of all-cause and expanded cardiovascular disease mortality (1.26, 1.08-1.46; 1.42, 1.12-1.79).

Sleep duration trajectories with constant high or unstable patterns may be associated with higher mortality.

The aim of our study is to estimate the associations and causalities of glucose metabolism traits of fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and 2-h glucose post-challenge (2hGlu) with sleep traits consisting of excessive daytime sleepiness (EDS), insomnia, and sleep duration.

We employed standard quantitative analysis procedures to assess the associations between sleep traits and glucose metabolism. Moreover, we acquired published genome-wide association studies (GWAS) summary statistics for these traits and conducted Mendelian randomization (MR) analyses to estimate their causal directions and effects. Inverse variance weighting (IVW) was employed as the primary approach, followed by sensitivity analyses.

A total of 116 studies with over 840,000 participants were included in the quantitative analysis. Our results revealed that participants with abnormal glucose metabolism had higher risks for EDS (OR [95% CI] = 1.37 [1.10,1.69]), insomnia (OR [95% CI] = 1.65 [1.24,2.20]), and both short and long sleep duration (OR [95% CI] = 1.35 [1.12,1.63]; OR [95% CI] = 1.38 [1.13,1.67] respectively). In addition, individuals with these sleep traits exhibited alterations in several glycemic traits compared with non-affected controls. In MR analysis, the primary analysis demonstrated causal effects of 2hGlu on risks of EDS (OR [95% CI] = 1.022 [1.002,1.042]) and insomnia (OR [95% CI] = 1.020[1.001,1.039]). Furthermore, FINS was associated with short sleep duration (OR [95% CI] = 1.043 [1.018,1.068]), which reversely presented a causal influence on HbA1c (β [95% CI] = 0.131 [0.022,0.239]). These results were confirmed by sensitivity analysis.

Our results suggested mutual risk and causal associations between the sleep traits and glycemic traits, shedding new light on clinical strategies for preventing sleep disorders and regulating glucose metabolism. Future studies targeting these associations may hold a promising prospect for public health.

The association of evening chronotype with cardiometabolic disease has been well established. However, the extent to which circadian rhythm disturbances independently result in risk remains unclear. This study aimed to investigate the cross-sectional and prospective longitudinal associations between chronotype and cardiometabolic risk among Chinese young adults.

From April to May 2019, a total of 1 135 young adults were selected to complete the self-administered questionnaire, and 744 fasting blood samples were collected to quantify cardiometabolic parameters. From April to May 2021, 340 fasting blood samples were collected to quantify cardiometabolic parameters. The Morning and Evening Questionnaire 5 (MEQ-5) was used to assess chronotype. The cardiometabolic (CM)-risk score was the sum of standardized Z scores based on gender for the 5 indicators: waist circumference (WC), mean arterial pressure (MAP), triglyceride (TG), homeostasis model assessment for insulin resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C), where the HDL-C is multiplied by-1. The generalized linear model was used to determine the cross-sectional and prospective longitudinal associations between chronotype and each cardiometabolic parameter.

Cross-sectional association analysis showed that lower MEQ-5 scores were correlated with higher fasting insulin (β=-1.420, 95%CI: -2.386~-0.453), higher HOMA-IR (β=-0.301, 95%CI: -0.507~-0.095), and higher CM risk score (β=-0.063, 95%CI: -0.122~-0.003), even after adjustment for covariates. Prospective longitudinal association analysis also showed that lower MEQ-5 scores were associated with 2 years later higher fasting glucose (β=-0.018, 95%CI: -0.034~-0.003), higher fasting insulin (β=-0.384, 95%CI: -0.766~-0.003), higher HOMA-IR (β=-0.089, 95%CI: -0.176~-0.002), and higher CM-risk score (β=-0.109, 95%CI: -0.214~-0.003) after adjustment for covariates.

Evening chronotype was significantly correlated with higher CM risk among young adults. Our findings suggest that biologically and socially affected sleep timing misalignment is a contributing factor to cardiovascular disease risk.

Despite significant improvements in longevity and quality of life associated with antiretroviral therapy, individuals with HIV still suffer from a higher burden of sleep and circadian disruption and inflammatory-based diseases than individuals without HIV. While melatonin is a hormone that has a role in sleep and circadian regulation and has anti-inflammatory properties, the overnight concentration of the urinary melatonin metabolite has not yet been reported in people with HIV.

The aim of this study was to compare the overnight urinary melatonin metabolite levels in women aged 35-70 years with HIV (n = 151) to a well-matched comparison group of women without HIV (n = 147). All women wore a wrist actigraphy monitor and completed daily diaries documenting sleep timing and use of medications and drugs or alcohol for 10 days. Participants collected their overnight urine near the end of the monitoring period.

Melatonin levels did not differ between women with or without HIV, but more than 40% of women had low levels of melatonin. Higher body mass index predicted lower levels of melatonin, and lower levels of melatonin were associated with lower sleep efficiency as assessed with wrist actigraphy.

These data lay the foundation for exploration of the longitudinal consequences of endogenous melatonin levels for inflammatory-based diseases in aging women with and without HIV. Future studies should consider the use of supplemental melatonin to improve sleep in women with lower levels of melatonin.

Cerebral ischemia and diabetes mellitus (DM) are common diseases that often coexist and interact with each other. DM doubles the risk of ischemic stroke, and cerebral ischemia causes stress-induced hyperglycemia. Most experimental stroke studies used healthy animals. Melatonin is neuroprotective against cerebral ischemia-reperfusion injury (CIRI) in non-DM, normoglycemic animals through anti-oxidant effect, anti-inflammation, and anti-apoptosis. Previous studies have also reported a negative correlation between hyperglycemia and urinary melatonin metabolite.

The present study investigated the effects of type 1 DM (T1DM) on CIRI in rats and the role of melatonin against CIRI in T1DM animals.

Our results revealed that T1DM aggravated CIRI, leading to greater weight loss, increased infarct volume, and worse neurological deficit. T1DM aggravated the post-CIRI activation of nuclear factor kappa B (NF-κB) pathway and increase in pro-apoptotic markers. A single intraperitoneal injection of melatonin at 10 mg/kg given 30 min before ischemia onset attenuated CIRI in T1DM rats, resulting in less weight loss, decreased infarct volume, and milder neurological deficit when compared with the vehicle group. Melatonin treatment achieved anti-inflammatory and anti-apoptotic effects with reduced NF-κB pathway activation, reduced mitochondrial cytochrome C release, decreased calpain-mediated spectrin breakdown product (SBDP), and decreased caspase-3-mediated SBDP. The treatment also led to fewer iNOS+ cells, milder CD-68+ macrophage/microglia infiltration, decreased TUNEL+ apoptotic cells, and better neuronal survival.

T1DM aggravates CIRI. Melatonin treatment is neuroprotective against CIRI in T1DM rats via anti-inflammatory and anti-apoptotic effects.

Glycemic variability is recognized as a significant factor contributing to the development of micro- and macrovascular complications in individuals with type 2 diabetes mellitus (T2DM). Numerous studies have shown that melatonin, a hormone involved in regulating various biological rhythms, including those related to glucose regulation, such as hunger, satiety, sleep, and circadian hormone secretion (ie, cortisol, growth hormone, catecholamines, and insulin), is deficient in individuals with T2DM. This raises an important question: Could melatonin replacement potentially reduce glycemic variability in these patients? This warrants investigation as a novel approach to improving glycemic control and reducing the risk of complications associated with T2DM.

We aimed to investigate whether melatonin replacement in individuals with T2DM who supposedly have melatonin deficiency can positively impact the regulation of insulin secretion rhythms and improve insulin sensitivity, ultimately resulting in a reduction in glycemic variability.

This study will use a crossover, randomized, double-blind, placebo-controlled trial design. Patients with T2DM in group 1 will receive 3 mg of melatonin at 9:00 PM in the first week, undergo a washout period in the second week, and receive a placebo in the third week (melatonin-washout-placebo). Group 2 will be randomized to receive a placebo-washout-melatonin sequence (3 mg). Capillary blood glucose levels will be measured at 6 different times before and after meals during the last 3 days of the first and third weeks. The study aims to compare the mean differences in blood glucose levels and the coefficient of glycemic variability in patients receiving melatonin and placebo during the first and third weeks. After analyzing the initial results, the number of needed patients will be recalculated. If the recalculated number is higher than 30, new participants will be recruited. Thirty patients with T2DM will be randomized into the 2 groups: melatonin-washout-placebo or placebo-washout-melatonin.

Participant recruitment took place between March 2023 to April 2023. In all, 30 participants were eligible and completed the study. We expect that patients will show different glycemic variability on the days they receive placebo or melatonin. Studies on melatonin and glycemic control have shown both positive and negative results. We hope that there will be a positive outcome regarding glycemic variability (ie, a reduction in glycemic variability), as melatonin has a well-described chronobiotic effect in the literature.

This study aims to determine whether melatonin supplementation can effectively reduce glycemic variability in patients with T2DM. The crossover design is necessary due to the multiple variables involved in the circadian variations of glucose, including diet, physical activity, sleep parameters, and pharmacological treatments. The relatively low cost of melatonin and its potential role in reducing the severe complications associated with T2DM have motivated this research effort. Furthermore, the indiscriminate use of melatonin in current times makes conducting this study essential to evaluate the effect of this substance in patients with T2DM.

Brazilian Registry of Clinical Trials RBR-6wg54rb; https://ensaiosclinicos.gov.br/rg/RBR-6wg54rb.

DERR1-10.2196/47887.

Type 2 Diabetes Mellitus (T2DM) has been the main category of metabolic diseases in recent years due to changes in lifestyle and environmental conditions such as diet and physical activity. On the other hand, the circadian rhythm is one of the most significant biological pathways in humans and other mammals, which is affected by light, sleep, and human activity. However, this cycle is controlled via complicated cellular pathways with feedback loops. It is widely known that changes in the circadian rhythm can alter some metabolic pathways of body cells and could affect the treatment process, particularly for metabolic diseases like T2DM. The aim of this study is to explore the importance of the circadian rhythm in the occurrence of T2DM via reviewing the metabolic pathways involved, their relationship with the circadian rhythm from two perspectives, lifestyle and molecular pathways, and their effect on T2DM pathophysiology. These impacts have been demonstrated in a variety of studies and led to the development of approaches such as time-restricted feeding, chronotherapy (time-specific therapies), and circadian molecule stabilizers.

Shift work can cause circadian cycles disturbances and misaligns the endogenous rhythms. The physiological variables are driven by the circadian system and, its misalignment, can impair the metabolic functions. Thus, the main objective of this study was to evaluate the metabolic alterations as a result of shift work and night work reported in articles published in the last 5 years, using the eligibility criteria both gender and indexed articles in English language. In order to execute this work, we perform a systematic review according to PRISMA guidelines and searched about Chronobiology Disorders and Night Work, both related to metabolism, in Medline, Lilacs, ScienceDirect and Cochrane. Cross-sectional, cohort and experimental studies with low risk of bias were included. We found a total of 132 articles, and, after the selection process, 16 articles remained to be analyzed. It was observed that shift work can cause circadian misalignment and, consequently, some metabolic parameters alterations such as an impaired glycemic control and insulin functioning, cortisol phase release, cholesterol fractions imbalance, changes in morphological indexes and melatonin secretion. There are some limitations, such as heterogenicity in used databases and the 5 years restriction period, because the effects of sleep disturbance may have been reported earlier. In conclusion, we suggest that shift work interferes with the sleep-wake cycle and eating patterns, which cause crucial physiological alterations that, together, can lead to metabolic syndrome.

Metabolic syndrome (MetS) is a constellation of several associated cardiometabolic risk factors that increase the risk of developing type 2 diabetes mellitus (T2DM), cardiovascular diseases, and mortality. The role of hormonal factors in the development of MetS is assumed. In women, an insulin-resistant state that is associated with polycystic ovarian syndrome and increased deposition of intra-abdominal adipose tissue promotes the development of MetS and increases cardiovascular risk. The neuroendocrine hormone melatonin is secreted mainly at night under the regulatory action of the suprachiasmatic nucleus in the hypothalamus. Melatonin secretion is influenced by exogenous factors such as light and seasons and endogenous factors such as age, sex, and body weight. At present, the role of melatonin in metabolic disorders in humans is not fully understood. In this review, we set out to analyze the relationship of melatonin with the main features of MetS in women. Data from experimental and clinical studies on the role of melatonin in glucose metabolism and on the involvement of melatonin in lipid disturbances in MetS are reviewed. The complex influence of melatonin on hypertension is discussed. The changes in melatonin, leptin, and ghrelin and their relation to various metabolic processes and vascular dysfunction are discussed.

The mammalian circadian clocks are entrained by environmental time cues, such as the light-dark cycle and the feeding-fasting cycle. In modern society, circadian misalignment is increasingly more common under the guise of shift work. Shift workers, accounting for roughly 20% of the workforce population, are more susceptible to metabolic disease. Exposure to artificial light at night and eating at inappropriate times of the day uncouples the central and peripheral circadian clocks. This internal circadian desynchrony is believed to be one of the culprits leading to metabolic disease. In this review, we discuss how alterations in the rhythm of gut microbiota and their metabolites during chronodisruption send conflicting signals to the host, which may ultimately contribute to disturbed metabolic processes. We propose two behavioral interventions to improve health in shift workers. Firstly, by carefully timing the moments of exposure to blue light, and hence shifting the melatonin peak, to improve sleep quality of daytime sleeping episodes. Secondly, by timing the daily time window of caloric intake to the biological morning, to properly align the feeding-fasting cycle with the light-dark cycle and to reduce the risk of metabolic disease. These interventions can be a first step in reducing the worldwide burden of health problems associated with shift work.

Little is known about the link between solar activity and variations in melatonin. In this study, we investigated if melatonin's major urinary metabolite, urinary 6-sulfatoxymelatonin (aMT6s), is lowest under periods of intense solar activity.

We investigated associations between high-energy solar particle events [Coronal Mass Ejection (CME) mass, speed and energy] on creatinine-adjusted aMT6s (aMT6sr) concentrations in 140 patients with chronic obstructive pulmonary disease (COPD) using up to four seasonal urine samples (n = 440). Mixed effect models with a random intercept for each subject were used to estimate associations, including effect modification attributable to diabetes, obesity, and reduced pulmonary function.

Higher values of CME were associated with reduced aMT6sr concentrations, with stronger associations in patients with diabetes. An interquartile range (IQR) increase in natural log CMEspeed averaged through two days before urine collection was associated with a reduction of 9.3% aMT6sr (95%CI: - 17.1%, - 0.8%) in aMT6sr. There was a greater reduction in aMT6sr in patients with diabetes (- 24.5%; 95%CI: - 35.9%, - 11.6%). In patients without diabetes there was no meaningful association (- 2.2%; 95%CI: - 12%, 8.4%). There were similar associations with CMEenergy and CMEmass. There was no effect modification attributable to reduced pulmonary function or obesity.

This is the first study in patients with COPD to demonstrate strong detrimental impact of high-energy solar particle events on aMT6sr, with greater associations in patients with diabetes. Since melatonin is an anti-oxidant, it is possible that adverse effects of intense solar activity may be attributable to a reduction in circulating melatonin and that patients with both COPD and diabetes may be more susceptible.

Light at night (LAN) has been associated with negative health consequences and metabolic risk factors. Little is known about the prevalence of LAN in older adults in the United States and its association with CVD risk factors. We tested the hypothesis that LAN in older age is associated with higher prevalence of individual CVD risk factors. Five hundred and fifty-two community-dwelling adults aged 63-84 years underwent an examination of CVD risk factor profiles and 7-day actigraphy recording for activity and light measures. Associations between actigraphy-measured LAN, defined as no light vs. light within the 5-hour nadir (L5), and CVD risk factors, including obesity, diabetes, hypertension, and hypercholesterolemia, were examined, after adjusting for age, sex, race, season of recording, and sleep variables. LAN exposure was associated with a higher prevalence of obesity (multivariable-adjusted odds ratio [OR] 1.82 [95% CI 1.26-2.65]), diabetes (OR 2.00 [1.19-3.43]), and hypertension (OR 1.74 [1.21-2.52]) but not with hypercholesterolemia. LAN was also associated with (1) later timing of lowest light exposure (L5-light) and lowest activity (L5-activity), (2) lower inter-daily stability and amplitude of light exposure and activity, and (3) higher wake after sleep onset. Habitual LAN in older age is associated with concurrent obesity, diabetes, and hypertension. Further research is needed to understand long-term effects of LAN on cardiometabolic risks.

Few observational studies have investigated the association of dietary antioxidant intake with post-stroke depression (PSD) risk. We used the cross-sectional and longitudinal design to investigate the independent and joint associations between dietary antioxidant intake and PSD risk and all-cause mortality.

Participants from the 2005-2014 National Health and Nutrition Examination Survey (NHANES) aged 20 years and older with stroke were included. Logistic and Cox regression analyses were used to assess the associations of dietary antioxidant intake, including vitamin A, vitamin C, vitamin E, zinc, selenium, and carotenoids, and composite dietary antioxidant index (CDAI) with PSD risk and all-cause mortality.

The highest quartile of dietary vitamin A (OR: 0.54, 95%CI: 0.32, 0.92), total carotenoids (OR: 0.56, 95%CI: 0.34, 0.94), and selenium intake (OR: 0.53, 95%CI: 0.31, 0.90) were associated with decreased PSD risk compared with those in the lowest quartile. The results showed a negative association between CDAI and PSD risk, with the lowest OR in the third quartiles (OR: 0.49, 95%CI: 0.30, 0.83). Furthermore, the highest quartile of dietary vitamin A (HR: 0.63, 95%CI: 0.45, 0.89), vitamin E (HR: 0.69, 95%CI: 0.48, 0.99), zinc (HR: 0.57, 95%CI: 0.40, 0.81), selenium (HR: 0.64, 95%CI: 0.46, 0.90), and total carotenoids (HR: 0.66, 95%CI: 0.47, 0.92) intake and CDAI (HR: 0.56, 95%CI: 0.39, 0.81) were associated with decreased all-cause mortality compared with those in the lowest quartile.

Increased intake of dietary antioxidant may protect from depressive symptoms and improve the prognosis of stroke patients.

Shift work is known to increase the risk of cardiometabolic diseases and mortality. We investigate the relationship between shift work schedules and cardiometabolic risk factors (smoking, hypertension, and obesity) and their association with cardiometabolic diseases (diabetes and cardiovascular diseases) in a multi-ethnic population from Singapore.

2469 participants from the Singapore-based Multi-Ethnic Cohort underwent physical and clinical assessments. Shift work schedules (morning, evening, night, and mixed) were assessed using a validated questionnaire.

Among shift workers, night shift workers had a significantly higher prevalence of smoking (54.5%), diabetes (27.3%), and cardiovascular events (14.1%). Compared to non-shift workers, workers in the night (OR = 2.10, 95%CI: 1.26-3.41) and mixed (OR = 1.74, 95%CI: 1.22-2.48) shift groups were more likely to be current smokers. A significant association between shift duration and smoking (OR = 1.02, 95%CI: 1.00-1.03) was also observed, with longer shift duration (in years) leading to an increase in smoking behavior. No significant associations were found between shift work schedules and hypertension, obesity (BMI), diabetes, and cardiovascular disease, as well as other cardiometabolic risk factors and diseases.

This study found that shift schedules and shift duration were most strongly associated with smoking status after covariate adjustments (age, gender, ethnicity, socioeconomic status, and work arrangement), with night and mixed shift types being strongly associated with current smoker status. As smoking is a modifiable risk factor for cardiometabolic disease, employers of shift workers should increase work-based health interventions to control smoking and promote a healthier workforce.

The global epidemic of obesity and type 2 diabetes parallels the rampant state of sleep deprivation in our society. Epidemiological studies consistently show an association between insufficient sleep and metabolic dysfunction. Mechanistically, sleep and circadian rhythm exert considerable influences on hormones involved in appetite regulation and energy metabolism. As such, data from experimental sleep deprivation in humans demonstrate that insufficient sleep induces a positive energy balance with resultant weight gain, due to increased energy intake that far exceeds the additional energy expenditure of nocturnal wakefulness, and adversely impacts glucose metabolism. Conversely, animal models have found that sleep loss-induced energy expenditure exceeds caloric intake resulting in net weight loss. However, animal models have significant limitations, which may diminish the clinical relevance of their metabolic findings. Clinically, insomnia disorder and insomnia symptoms are associated with adverse glucose outcomes, though it remains challenging to isolate the effects of insomnia on metabolic outcomes independent of comorbidities and insufficient sleep durations. Furthermore, both pharmacological and behavioral interventions for insomnia may have direct metabolic effects. The goal of this review is to establish an updated framework for the causal links between insufficient sleep and insomnia and risks for type 2 diabetes and obesity.

This short review aimed at (i) providing an update on the health benefits associated with melatonin supplementation, while (ii) considering future potential research directions concerning melatonin supplementation use relative to Coronavirus disease of 2019 (COVID-19). A narrative review of the literature was undertaken to ascertain the effect of exogenous melatonin administration on humans. Night-time melatonin administration has a positive impact on human physiology and mental health. Indeed, melatonin (i) modulates the circadian components of the sleep-wake cycle; (ii) improves sleep efficiency and mood status; (iii) improves insulin sensitivity; and (iv) reduces inflammatory markers and oxidative stress. Melatonin has also remarkable neuroprotective and cardioprotective effects and may therefore prevent deterioration caused by COVID-19. We suggest that melatonin could be used as a potential therapy in the post-COVID-19 syndrome, and therefore call for action the research community to investigate on the potential use of exogenous melatonin to enhance the quality of life in patients with post-COVID-19 syndrome. See also Figure 1(Fig. 1).

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

In a world in which life expectancy is increasing, understanding and promoting healthy aging becomes a contemporary demand. In the elderly, a sterile, chronic and low-grade systemic inflammation known as "inflammaging" is linked with many age-associated diseases. Considering sarcopenia as a loss of strength and mass of skeletal muscle related to aging, correlations between these two terms have been proposed. Better knowledge of the immune system players in skeletal muscle would help to elucidate their implications in sarcopenia. Characterizing the activators of damage sensors and the downstream effectors explains the inference with skeletal muscle performance. Sarcopenia has also been linked to chronic diseases such as diabetes, metabolic syndrome and obesity. Implications of inflammatory signals from these diseases negatively affect skeletal muscle. Autophagic mechanisms are closely related with the inflammasome, as autophagy eliminates stress signaling sent by damage organelles, but also acts with an immunomodulatory function affecting immune cells and cytokine release. The use of melatonin, an antioxidant, ROS scavenger and immune and autophagy modulator, or senotherapeutic compounds targeting senescent cells could represent strategies to counteract inflammation. This review aims to present the many factors regulating skeletal muscle inflammaging and their major implications in order to understand the molecular mechanisms involved in sarcopenia.

It has been shown that melatonin plays a general beneficial role in type 2 diabetes in rodents but its role in humans is controversial. In the present study, we investigated the association between serum melatonin and type 2 diabetes risk in a southern Chinese population in a case-control study. We also examined the role of gut microbiota in this relationship.

Individuals with type 2 diabetes (cases) and healthy individuals (controls) (n=2034) were recruited from a cross-sectional study and were matched for age and sex in a case-control study. The levels of serum melatonin were measured and the association between serum melatonin and type 2 diabetes risk was examined using a multivariable logistic regression model. We further conducted a rigorously matched case-control study (n=120) in which gut microbial 16S rRNA was sequenced and metabolites were profiled using an untargeted LC-MS/MS approach.

Higher levels of serum melatonin were significantly associated with a lower risk of type 2 diabetes (OR 0.82 [95% CI 0.74, 0.92]) and with lower levels of fasting glucose after adjustment for covariates (β -0.25 [95% CI -0.38, -0.12]). Gut microbiota exhibited alteration in the individuals with type 2 diabetes, in whom lower levels of serum melatonin, lower α- and β-diversity of gut microbiota (p<0.05), greater abundance of Bifidobacterium and lower abundance of Coprococcus (linear discriminant analysis [LDA] >2.0) were found. Seven genera were correlated with melatonin and type 2 diabetes-related traits; among them Bifidobacterium was positively correlated with serum lipopolysaccharide (LPS) and IL-10, whereas Coprococcus was negatively correlated with serum IL-1β, IL-6, IL-10, IL-17, TNF-α and LPS (Benjamini-Hochberg-adjusted p value [false discovery rate (FDR)] <0.05). Moreover, altered metabolites were detected in the participants with type 2 diabetes and there was a significant correlation between tryptophan (Trp) metabolites and the melatonin-correlated genera including Bifidobacterium and Coprococcus (FDR<0.05). Similarly, a significant correlation was found between Trp metabolites and inflammation factors, such as IL-1β, IL-6, IL-10, IL-17, TNF-α and LPS (FDR<0.05). Further, we showed that Trp metabolites may serve as a biomarker to predict type 2 diabetes status (AUC=0.804).

A higher level of serum melatonin was associated with a lower risk of type 2 diabetes. Gut microbiota-mediated melatonin signalling was involved in this association; especially, Bifidobacterium- and Coprococcus-mediated Trp metabolites may be involved in the process. These findings uncover the importance of melatonin and melatonin-related bacteria and metabolites as potential therapeutic targets for type 2 diabetes.

Melatonin (MT) has been reported to control and prevent Alzheimer's disease (AD) in the clinic; however, the effect and mechanism of MT on AD have not been specifically described. Therefore, the main purpose of this meta-analysis was to explore the effect and mechanism of MT on AD models by studying behavioural indicators and pathological features. Seven databases were searched and 583 articles were retrieved. Finally, nine studies (13 analyses, 294 animals) were included according to pre-set criteria. Three authors independently judged the selected literature and the methodological quality. Meta-analysis showed that MT markedly ameliorated the learning ability by reducing the escape latency (EL), and the memory deficit was significantly corrected by increasing the dwell time in the target quadrant and crossings over the platform location in the Morris Water Maze (MWM). Among the pathological features, subgroup analysis found that MT may ease the symptoms of AD mainly by reducing the deposition of Aβ40 and Aβ42 in the cortex. In addition, MT exerted a superior effect on ameliorating the learning ability of senescence-related and metabolic AD models, and corrected the memory deficit of the toxin-induced AD model. The study was registered at PROSPERO (CRD42021226594).