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The human circadian system plays a vital role in many physiological processes, and circadian rhythms are found in virtually all tissues and organs. The disruption of circadian rhythms may lead to adverse health outcomes. Evidence from recent population‐based studies was reviewed because they represent real‐world behavior and can be useful in developing future studies to reduce the risk of adverse health conditions, including cardiovascular diseases, obesity, and diabetes mellitus, which may occur because of circadian disruption. An electronic search in PubMed and Web of Science (2012–2022) was performed. Selected articles were based on specific inclusion and exclusion criteria. Five factors that may disrupt circadian rhythm alignment are discussed: shift work, late chronotype, late sleep timing, sleep irregularity, and late meal timing. Evidence from observational studies of these circadian disruptors suggests potential detrimental effects on cardiometabolic health, including higher BMI/obesity, higher blood pressure, greater dyslipidemia, greater inflammation, and diabetes. Future research should identify the specific underlying pathways in order to mitigate the health consequences of shift work. Furthermore, optimal sleep and mealtimes for metabolic health can be explored in intervention studies. Lastly, it is important that the timing of external environmental cues (such as light) and behaviors that influence circadian rhythms are managed. [ABSTRACT FROM AUTHOR]

Background: In addition to quantity and quality, meal timing and eating duration are additional dietary characteristics that impact cardiometabolic health. Given that cardiometabolic health disparities exist among racial and ethnic groups, we examined whether meal timing and eating duration are additional diet-related differences among racial and ethnic groups. Methods: Participants (n = 13,084) were adults (≥20 years) from the National Health and Nutrition Examination (NHANES, 2011–2018) Survey. Times of first and last meal and the interval between them (eating duration) were derived from two 24-h dietary recalls. Multiple linear regression analyses compared these variables among race and ethnicity after adjusting for potential confounders. Results: Compared to non-Hispanic White adults, the first mealtime was significantly later for Mexican American (23 min), Non-Hispanic Asian (15 min), Non-Hispanic Black (46 min), and Other Hispanic (20 min) and Other Racial (14 min) adults (all p < 0.05). Mexican American and Non-Hispanic Asian adults had a significantly different last mealtime by 13 min earlier and 25 min later, respectively, compared to Non-Hispanic White adults. Compared to Non-Hispanic White adults, the mean eating duration was shorter for other Hispanic (20 min), Mexican American (36 min), and Non-Hispanic Black (49 min) adults. Conclusions: Meal timing and eating duration are additional dietary characteristics that vary significantly among racial and ethnic groups. [ABSTRACT FROM AUTHOR]

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes at individual and population levels. Evidence points to a bidirectional relationship, in that circadian disruption increases disease severity and many diseases can disrupt circadian rhythms. Importantly, circadian disruption can increase the risk for the expression and development of neurologic, psychiatric, cardiometabolic, and immune disorders. Thus, harnessing the rich findings from preclinical and translational research in circadian biology to enhance health via circadian-based approaches represents a unique opportunity for personalized/precision medicine and overall societal well-being. In this Review, we discuss the implications of circadian disruption for human health using a bench-to-bedside approach. Evidence from preclinical and translational science is applied to a clinical and population-based approach. Given the broad implications of circadian regulation for human health, this Review focuses its discussion on selected examples in neurologic, psychiatric, metabolic, cardiovascular, allergic, and immunologic disorders that highlight the interrelatedness between circadian disruption and human disease and the potential of circadian-based interventions, such as bright light therapy and exogenous melatonin, as well as chronotherapy to improve and/or modify disease outcomes. [ABSTRACT FROM AUTHOR]

It is well established that the oldest chronotype questionnaire, the morningness-eveningness questionnaire (MEQ), has significant heritability, and several associations have been reported between MEQ score and polymorphisms in candidate clock genes, a number of them reproducibly across populations. By contrast, there are no reports of heritability and genetic associations for the Munich chronotype questionnaire (MCTQ). Recent genome-wide association studies (GWAS) from large cohorts have reported multiple associations with chronotype as assessed by a single self-evaluation question. We have taken advantage of the availability of data from all these instruments from a single sample of 597 participants from the Brazilian Baependi Heart Study. The family-based design of the cohort allowed us to calculate the heritability (h2) for these measures. Heritability values for the best-fitted models were 0.37 for MEQ, 0.32 for MCTQ, and 0.28 for single-question chronotype (MEQ Question 19). We also calculated the heritability for the two major factors recently derived from MEQ, "Dissipation of sleep pressure" (0.32) and "Build-up of sleep pressure" (0.28). This first heritability comparison of the major chronotype instruments in current use provides the first quantification of the genetic component of MCTQ score, supporting its future use in genetic analysis. Our findings also suggest that the single chronotype question that has been used for large GWAS analyses captures a larger proportion of the dimensions of chronotype than previously thought. [ABSTRACT FROM AUTHOR]

Studying communities at different stages of urbanisation and industrialisation can teach us how timing and intensity of light affect the circadian clock under real‐life conditions. We have previously described a strong tendency towards morningness in the Baependi Heart Study, located in a small rural town in Brazil. Here, we tested the hypothesis that this morningness tendency is associated with early circadian phase based on objective measurements (as determined by dim light melatonin onset, DLMO, and activity) and light exposure. We also analysed how well the previously collected chronotype questionnaire data were able to predict these DLMO values. The average DLMO observed in 73 participants (40 female) was 20:03 ± 01:21, SD, with an earlier average onset in men (19:38 ± 01:16) than in women (20:24 ± 01:21; P ≤.01). However, men presented larger phase angle between DLMO and sleep onset time as measured by actigraphy (4.11 hours vs 3.16 hours; P ≤.01). Correlational analysis indicated associations between light exposure, activity rhythms and DLMO, such that early DLMO was observed in participants with higher exposure to light, higher activity and earlier light exposure. The strongest significant predictor of DLMO was morningness‐eveningness questionnaire (MEQ) (beta=−0.35, P ≤.05), followed by age (beta = −0.47, P ≤.01). Sex, light exposure and variables derived from the Munich chronotype questionnaire were not significant predictors. Our observations demonstrate that both early sleep patterns and earlier circadian phase have been retained in this small rural town in spite of availability of electrification, in contrast to metropolitan postindustrial areas. [ABSTRACT FROM AUTHOR]

Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38-73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86-2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24-1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20-1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19-1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18-1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004-1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00-1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02-1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility. [ABSTRACT FROM AUTHOR]

Summary: Physiological evidence suggests that sleep modulates kidney function. Our objective was to examine the cross‐sectional association between kidney function and objectively‐estimated habitual sleep duration, quality and timing in a cohort of patients with mild to moderate chronic kidney disease. This study involved two US clinical centers of the Chronic Renal Insufficiency Cohort (CRIC) study, including 432 participants in a CRIC ancillary sleep study. Habitual sleep duration, quality and timing were measured using wrist actigraphy for 5–7 days. Validated sleep questionnaires assessed subjective sleep quality, daytime sleepiness and risk of sleep apnea. Kidney function was assessed with the estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation, and the urinary protein to creatinine ratio. Lower estimated glomerular filtration rate was associated with shorter sleep duration (−1.1 mL min−1 1.73 m−2 per hour less sleep, P = 0.03), greater sleep fragmentation (−2.6 mL min−1 1.73 m−2 per 10% higher fragmentation, P < 0.001) and later timing of sleep (−0.9 mL min−1 1.73 m−2 per hour later, P = 0.05). Higher protein to creatinine ratio was also associated with greater sleep fragmentation (approximately 28% higher per 10% higher fragmentation, P < 0.001). Subjective sleep quality, sleepiness and persistent snoring were not associated with estimated glomerular filtration rate or protein to creatinine ratio. Thus, worse objective sleep quality was associated with lower estimated glomerular filtration rate and higher protein to creatinine ratio. Shorter sleep duration and later sleep timing were also associated with lower estimated glomerular filtration rate. Physicians treating patients with chronic kidney disease should consider inquiring about sleep and possibly sending for clinical sleep assessment. Longitudinal and interventional trials are needed to understand causal direction. [ABSTRACT FROM AUTHOR]

The circadian system is known to play a role in glucose metabolism. Chronotype reflects the interindividual variability in the phase of entrainment. Those with later chronotype typically prefer later times in the day for different activities such as sleep or meals. Later chronotype has been shown to be associated with metabolic syndrome, increased diabetes risk and poorer glycemic control in type 2 diabetes patients. In addition, “social jetlag”, a form of circadian misalignment due to a mismatch between social rhythms and the circadian clock, has been shown to be associated with insulin resistance. Other sleep disturbances (insufficient sleep, poor sleep quality and sleep apnea) have also been shown to affect glucose metabolism. In this study, we explored whether there was a relationship between chronotype, social jetlag and hemoglobin A1c (HbA1c) levels in prediabetes patients, independent of other sleep disturbances. A cross-sectional study was conducted at the Department of Family Medicine, Ramathibodi Hospital, Bangkok, from October 2014 to March 2016 in 1014 non-shift working adults with prediabetes. Mid-sleep time on free day adjusted for sleep debt (MSFsc) was used as an indicator of chronotype. Social jetlag was calculated based on the absolute difference between mid-sleep time on weekdays and weekends. The most recent HbA1c values and lipid levels were retrieved from clinical laboratory databases. Univariate analyses revealed that later MSFsc (p= 0.028) but not social jetlag (p= 0.48) was significantly associated with higher HbA1c levels. Multivariate linear regression analysis was applied to determine whether an independent association between MSFsc and HbA1c level existed. After adjusting for age, sex, alcohol use, body mass index (BMI), social jetlag, sleep duration, sleep quality and sleep apnea risk, later MSFsc was significantly associated with higher HbA1c level (B = 0.019, 95% CI: 0.00001, 0.038,p= 0.049). The effect size of one hour later MSFsc on HbA1c (standardized coefficient = 0.065) was approximately 74% of that of the effect of one unit (kg/m2) increase in BMI (standardized coefficient = 0.087). In summary, later chronotype is associated with higher HbA1c levels in patients with prediabetes, independent of social jetlag and other sleep disturbances. Further research regarding the potential role of chronotype in diabetes prevention should be explored. [ABSTRACT FROM PUBLISHER]

Significant questions remain unanswered regarding the genetic versus environmental contributions to racial/ethnic differences in sleep and circadian rhythms. We addressed this question by investigating the association between diurnal preference, using the morningness–eveningness questionnaire (MEQ), and genetic ancestry within the Baependi Heart Study cohort, a highly admixed Brazilian population based in a rural town. Analysis was performed using measures of ancestry, using the Admixture program, and MEQ from 1,453 individuals. We found an association between the degree of Amerindian (but not European of African) ancestry and morningness, equating to 0.16 units for each additional percent of Amerindian ancestry, after adjustment for age, sex, education, and residential zone. To our knowledge, this is the first published report identifying an association between genetic ancestry and MEQ, and above all, the first one based on ancestral contributions within individuals living in the same community. This previously unknown ancestral dimension of diurnal preference suggests a stratification between racial/ethnic groups in an as yet unknown number of genetic polymorphisms. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To examine whether chronotype and daily caloric distribution are associated with glycemic control in patients with type 2 diabetes independently of sleep disturbances. RESEARCH DESIGN AND METHODS--Patients with type 2 diabetes had a structured interview and completed questionnaires to collect information on diabetes history and habitual sleep duration, quality, and timing. Shift workers were excluded. A recently validated construct derived from mid-sleep time on weekends was used as an indicator of chronotype. One-day food recall was used to compute the temporal distribution of caloric intake. Hierarchical linear regression analyses controlling for demographic and sleep variables were computed to determine whether chronotype was associated with HbA1c values and whether this association was mediated by a higher proportion of caloric intake at dinner. RESULTS--We analyzed 194 completed questionnaires. Multiple regression analyses adjusting for age, sex, race, BMI, insulin use, depressed mood, diabetes complications, and perceived sleep debt found that chronotype was significantly associated with glycemic control (P = 0.001). This association was partially mediated by a greater percentage of total daily calories consumed at dinner. CONCLUSIONS--Later chronotype and larger dinner were associated with poorer glycemic control in patients with type 2 diabetes independently of sleep disturbances. These results suggest that chronotype may be predictive of disease outcomes and lend further support to the role of the circadian system in metabolic regulation. [ABSTRACT FROM AUTHOR]

There is a significant interest in the contribution of the circadian timing system to individual differences in a wider range of behaviour. This is in part because sleep complaints and disturbances of the circadian timing system are common in psychiatric disorders. Based on diurnal preference, people can be divided into chronotypes with demonstrated differences in sleep-wake patterns and a variety of circadian rhythms, behavioral rhythms, and diurnal variation in mood. Specifically, greater eveningness has been related to greater depression. The human PER3 gene contains a variable number tandem repeat (VNTR) which is associated with diurnal preference: the longer allele (five tandem repeats) has been reported to associate with greater morningness, and the shorter allele (four tandem repeats) with greater eveningness. We have investigated the PER3 polymorphism and its relationship to sleep, circadian and depression characteristics in a Brazilian family-based cohort. Baependi is a small rural town in Brazil that provides a window of opportunity to study the influence of sleep circadian patterns in a highly admixed rural population with a conservative lifestyle. Here, we studied 786 subjects (mean age±SD 46.5±16.2, 42% female). Blood samples were collected from all participants. The Per3 length polymorphism was genotyped using PCR followed by gel electrophoresis. We tested for associations between the PER3 polymorphism and sleep characteristics, daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire, respectively. Depressive symptoms were assessed using the Beck Depression Inventory [BDI-II]). Our genotyping data showed that 36% of the subjects were homozygous for the shorter allele (4/4), 51% of the participants were heterozygous (4/5) and 12% of the subjects were homozygous for the longer allele (5/5). Allele frequency was 0.62 for the 4-repeat and a 0.38 for the 5-repeat. The percentages of the chronotypes Morning type (M-type), Neither type (N-type) and Evening type (E-type) were 5%, 46% and 7%, respectively. We observed an increase of the depression symptoms in evening types [F(2, 1014)=4.8, p=0.007]. On the other hand, no such associations were observed the PER3 genotype. There were no significant differences in the MEQ score [F(2, 317)=0.46, p=0.63], daytime sleepiness [(F(2, 317)=0.23, p=0.79)], sleep efficiency [(F(2, 317)=2.59, p=0.07)] and sleep characteristics [(F(2, 317)=1.92, p=0.14)] between the PER3 genotypes. We observed an association between eveningness and depression. Identifying factors contributing to individual differences in sleep and to describe how these factors are associated with physiological and psychological profiles may aid our understanding of the role of sleep and the circadian system in mental health. On the other hand, we were not able to replicate the association between the PER3 VNTR polymorphism and chronotype, which has been confirmed independently in multiple populations worldwide (including in Brazil). Neither did we observe any association with depression. CNPq – PVE 400791/2014-5. [ABSTRACT FROM AUTHOR]