Association between Circadian Rhythm-Disturbing Factors and Metabolic Syndrome in Korean Adults: Korea National Health and Nutrition Examination Survey (2016–2020)
Article information
Abstract
Background
Circadian misalignment is associated with metabolic syndrome. This study aimed to examine the association between circadian rhythm-disturbing factors and metabolic syndrome.
Methods
We used data from the 7th and 8th Korea National Health and Nutrition Examination Survey conducted between 2016 and 2020, which surveyed 16,253 individuals. Circadian rhythm-disturbing factors were defined as follows: sleep duration outside the reference group (6–8 hours), irregular breakfast, shift work, and physical inactivity. The adjusted odds ratio (aOR) for metabolic syndrome was calculated based on the number of circadian rhythm-disturbing factors present in adults over the age of 19 years.
Results
Among a total of 16,253 participants (mean age 48.2±15 years), metabolic syndrome was found in 5,237 participants (29.3 %). The participants were classified into three categories based on the number of circadian rhythm-disturbing factors as follows: 2,627 (15.6%) did not have any factors, 6,406 (38.13%) had one factor, and 7,220 (46.3%) had two or more factors. Participants with a single circadian rhythm-disturbing factor were 21% more likely to have metabolic syndrome (aOR, 1.21; 95% confidence interval [CI], 1.08–1.36), and participants with two or more factors were 27% more likely to have metabolic syndrome (aOR, 1.27; 95% CI, 1.12–1.43).
Conclusion
Circadian rhythm-disturbing factors were significantly associated with the prevalence of metabolic syndrome in Korean adults. This finding has potential clinical implications for maintaining circadian rhythms by avoiding certain factors to prevent metabolic syndrome. Further studies are required to confirm these findings.
INTRODUCTION
The circadian rhythm controls many aspects of physiological function in a 24-hour cycle, including the sleep-wake cycle, blood pressure, heart rate, body temperature, and hormone regulation [1]. This rhythm is governed by the central clock, located in the suprachiasmatic nucleus of the hypothalamus, as well as peripheral clocks throughout the body. Certain external exposures act as synchronizers of both the central and peripheral clocks, known as “zeitgebers” (derived from the German word “zeitgeber,” meaning time-giver) [2]. The most powerful zeitgeber is the cycle of light and dark exposure [3]. Additionally, eating patterns and physical activity have also been recognized as important zeitgebers that play a significant role in circadian rhythm alignment [4,5].
Technological advances have dramatically changed human lifestyles, allowing people to work and eat during the evening and night in contrast to traditional daytime routines [6]. However, these lifestyle changes disturb the circadian rhythm, leading to circadian misalignment, which is associated with obesity, type 2 diabetes, cardiovascular disease, and hypertension—all of which are components of metabolic syndrome [7]. Several previous studies have shown that circadian rhythm-disturbing factors such as short sleep duration, eating patterns, shift work, or physical inactivity are associated with an increased risk of metabolic syndrome by affecting circadian rhythm alignment [8-11]. Insufficient sleep, characterized by its impact on circadian rhythms, has been associated with metabolic disturbances including obesity and insulin resistance [8]. Irregular eating patterns, particularly the habit of skipping breakfast, can influence circadian rhythm alignment and metabolic flexibility, potentially contributing to the development of metabolic syndrome [9]. The prevalence of non-traditional working hours in shift work disrupts circadian rhythms, impacting metabolic health and contributing to the potential development of metabolic syndrome [10]. Furthermore, the absence of physical activity, which serves as a synchronizer for circadian rhythm, may disrupt alignment and lead to metabolic imbalances [11]. This study identified four circadian rhythm disruptors—inadequate sleep duration, irregular eating patterns, shift work, and physical inactivity. These were selected based on the theoretical premise that they significantly influence individuals in modern society, and that their cumulative impact may substantially increase their association with metabolic syndrome. Kim et al. [12] reported that an increased number of these circadian rhythm-disrupting factors is associated with higher likelihood of developing abdominal obesity. Despite considerable efforts, studies investigating the relationship between various circadian rhythm-disrupting lifestyles and metabolic syndromes are insufficient, and integrated studies on circadian rhythm disruptors have not been conducted. Therefore, this study is the first attempt to comprehensively address the individual effects of circadian rhythm-disrupting factors and their cumulative impact on the prevalence of metabolic syndrome. Using this approach, we aimed to better understand the influence of circadian rhythm-disrupting lifestyle patterns on the occurrence of metabolic syndrome.
METHODS
1. Data Source and Study Population
This study utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES), conducted between 2016 and 2020. The KNHANES is a nationwide, population-based, cross-sectional survey and health examination conducted by the Korea Disease Control and Prevention Agency. The survey employs nationally representative samples from the general Korean population and a stratified multistage probability sampling design to yield representative data. It conducts health interviews for acquisition of details on participants’ general health, medical history, lifestyle habits, and behaviors, including healthcare patterns. Behavioral and nutritional surveys are used to gather information on dietary habits, nutritional intake, and activity levels, including details such as meal frequency, food consumption, exercise, and activity levels. Medical examinations are used to collect data on physiological status and health indicators, including parameters such as blood pressure, blood glucose levels, lipid profiles, body mass index, and specific disease diagnoses. This study used data of the participants of KNHANES VII and VIII (n=39,738). Among the 39,738 participants, we included adults aged >19 years (n=32,128). After excluding participants with missing values in major variables such as metabolic syndrome components, sleep duration, breakfast frequency, working pattern, and physical activity, 16,253 of the study population were selected for the final analysis. This study was conducted after submitting a request for raw data and a summary of the use plan on the KNHANES website of the Korea Centers for Disease Control and Prevention (currently, Korea Disease Control and Prevention Agency) and obtaining approval for the use of the data. The study was approved by the Institutional Review Board (IRB) of Samsung Medical Center (IRB no., SMC 2023-01-099; IRB examination exemption approved, 2023.01.27). The requirement for informed consent from individual patients was omitted because of the retrospective design of this study.
2. Covariates
The variables in this study were recorded using a self-administered questionnaire. Sleep duration was classified as <6 hours, 6–8 hours, and >8 hours. Breakfast frequency was classified as regular breakfast (5–7 times a week) or irregular (less than 5 times a week). Working patterns were classified as day work (6 AM to 6 PM) and shift work. Shift workers were participants who reported participating in evening shift work (2 PM to midnight), night shift work (9 PM to 8 AM), or other types of work (regular day-night shifts, 24-hour rotating shifts, split shifts, or irregular shifts).
Physical activity was classified as physical activity (>600 metabolic equivalents [METs]/min/wk) or physical inactivity (<600 METs/min/wk).
Circadian rhythm-disturbing factors were as follows: sleep duration outside the reference group (6–8 hours), irregular breakfast, shift work, and physical inactivity. Individuals were classified into three groups: those with none of these factors, those with one factor, or those with two or more of the above factors.
Regarding sociodemographic and health behavior variables, participants were categorized according to age into the following groups: 19–29 years, 30–39 years, 40–49 years, 50–59 years, 60–69 years, and ≥70 years. Marital status was categorized as the presence or absence of a spouse. Education was categorized as middle school or lower, high school or higher, or college or higher. Income level was divided into low, middle-low, middle-high, and high quartiles. Income level was divided into low, middle-low, middle-high, and high quartiles. Smoking status was classified as current smoker, ex-smoker, or non-smoker. Drinking behavior was categorized as high-risk drinking (if the average amount of alcohol consumed per episode was 7 or more cups for men and 5 or more cups for women and if one drank more than twice a week), normal drinking (drinking more than once a month but without consuming high-risk amount alcohol per episode), and non-drinking (drinking less than once a month).
3. Definition of Metabolic Syndrome
Metabolic syndrome was determined based on the modified National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III) criteria [13]. Five items were considered as diagnostic criteria for metabolic syndrome: (1) waist circumference ≥90 cm in men and ≥80 cm for women (Asian cutoff points); (2) triglyceride level ≥150 mg/dL; (3) high-density lipoprotein cholesterol <40 mg/d for men and <50 mg/d for women; (4) systolic/diastolic blood pressure ≥130/85 mm Hg or use of anti-hypertensive medications; and (5) fasting blood glucose ≥100 mg/dL or use of anti-diabetic medications. The modified NCEP ATP III criteria suggest that the cut-off points of waist circumference should be applied according to ethnicity. Metabolic syndrome was diagnosed if three or more of the five metabolic syndrome components were present.
4. Statistical Analysis
The chi-square test (Rao-Scott χ2 test) was used to verify whether there was a significant difference in general characteristics and the prevalence of metabolic syndrome among the three groups based on the number of circadian rhythm-disturbing factors. To reflect demographic characteristics as much as possible, an analysis was conducted by considering the weights of 16,253 study participants. Logistic regression analysis was used to investigate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for the association between an increased number of circadian rhythm-disturbing factors and metabolic syndrome. The Cochrane-Armitage trend test was used to obtain the P-value for the trend. A P-value of <0.05 was considered statistically significant. Statistical analyses were performed using the IBM SPSS ver. 27.0 (IBM Corp., Armonk, NY, USA).
RESULTS
Table 1 provides the descriptive characteristics of the study population based on the number of circadian rhythm-disturbing factors. Among the 16,253 participants (with an average age of 48.2±15 years), 5,237 individuals were diagnosed with metabolic syndrome (29.27%). The number of participants without any disturbing factors was 2,627 (15.58%), with one disturbing factor were 6,406 (38.13%), and with more than two disturbing factors were 7,220 (46.29%). Regarding the circadian rhythm-disturbing factors, 2,209 (13.5%) reported sleeping <6 hours, 6,706 (47.4%) had irregular breakfast habits, 1,997 (17.9%) were engaged in shift work, and 8,947 (51.7%) were physically inactive.
Descriptive characteristics of study participants according to the number of circadian rhythm-disturbing factors
Table 2 presents the adjusted analysis that evaluated the association between the number of circadian rhythm-disturbing factors and metabolic syndrome. The risk for metabolic syndrome was higher in participants with one circadian rhythm-disturbing factor (aOR, 1.21; 95% CI, 1.08–1.36) and two or more factors (aOR, 1.27; 95% CI, 1.12–1.43) than in those without any circadian rhythm-disturbing factor (P-value <0.001).
OR and 95% CI for metabolic syndrome according to the number of circadian rhythm-disturbing factors
Separately, the risk of metabolic syndrome was higher in those with sleep duration of <6 hours (aOR, 1.25; 95% CI, 1.11–1.40) than in those with sleep duration of 6–8 hours. Similarly, the risk of metabolic syndrome was higher for irregular breakfast (aOR, 1.14; 95% CI, 1.03–1.25) than for regular breakfast. However, shift work showed decreased risk of metabolic syndrome compared to day work (evening worker: aOR, 0.94; 95% CI, 0.81–1.10; night worker: aOR, 0.68; 95% CI, 0.50–0.93; any other worker: aOR, 0.73; 95% CI, 0.60–0.88). Physical inactivity showed a higher risk of metabolic syndrome (aOR, 1.13; 95% CI, 1.04–1.24) compared to physical activity (Table 3).
Circadian rhythm-disturbing factors associated with the risk of metabolic syndrome
DISCUSSION
The present study revealed that all circadian rhythm-disturbing factors, except shift work, exhibited a significant correlation with the probability of developing metabolic syndrome. Additionally, as the number of factors disrupting the circadian rhythm increased, the prevalence of metabolic syndrome also increased. These results add to the previous findings that increased circadian rhythm-disturbing factors contribute to an elevated risk of metabolic disturbances. In modern society, many individuals have lifestyles that disrupt their circadian rhythms. Many studies suggest that circadian misalignment induced by mistimed light exposure, insufficient sleep, or mistimed food intake adversely affects metabolism [7]. Our study, based on data representing contemporary trends in Korea, revealed that individuals with such disrupted lifestyles are prevalent.
The primary factor that disrupts the circadian rhythm is short sleep duration, with inappropriate sleep duration being associated with various adverse metabolic changes, including obesity, type 2 diabetes, and early mortality [8]. In previous meta-analyses, cross-sectional studies have reported a U-shaped distribution between people with normal sleep time and those with short or long sleep time, showing an increased risk of metabolic syndrome. However, longitudinal studies have associated short sleep with a higher risk of metabolic syndrome, but did not find a similar association with long sleep [10]. In this study, the group with <6 hours of sleep showed a higher prevalence of metabolic syndrome than that of the group with 6–8 hours of sleep. However, the group with <8 hours of sleep did not show a similar pattern. Habitually short sleep, typically defined as <6 hours per night, disrupts the circadian rhythm, causing negative hormonal changes that affect metabolism and hinder autonomic balance. This can activate the sympathetic nervous system and induce cortisol dysregulation, leading to an increased risk of high blood pressure and contributing to insulin resistance and visceral adiposity [14]. In addition, lack of sleep promotes appetite by altering the appetite-suppressing hormone leptin and appetite-boosting hormone ghrelin, generating a preference for a calorie-rich diet and consequently increasing the risk of obesity and type 2 diabetes [13].
The second factor that disrupts the circadian rhythm is skipping breakfast. Previous studies have identified an association between skipping breakfast and obesity, indicating that skipping breakfast increases the risk of obesity [9]. In this study, the prevalence of metabolic syndrome was higher in the irregular breakfast group than in the regular breakfast group. The timing of nutrition can influence the circadian rhythm, which in turn affects the metabolic conversion between lipid and carbohydrate oxidation, as well as glucose metabolism [15,16]. Breakfast skipping leads to the development of metabolic inflexibility by increasing postprandial fat oxidation at lunchtime despite increased insulin concentrations, which could contribute to metabolic impairment [17]. Additionally, breakfast skipping results in subsequent unhealthy eating habits during lunch and dinner and an increase in the average 24-hour blood sugar level [18]. Even when consuming the same amount of energy per day, a higher percentage of energy intake during dinner has been associated with a greater risk of metabolic syndrome [17]. Moreover, eating at night lowers fat oxidation compared to that during breakfast, which leads to fat accumulation [16].
The third factor was shift work, which is an increasingly common work pattern worldwide. According to a recent meta-analysis, night shift work is significantly associated with a variety of unhealthy outcomes, including metabolic syndrome [19]. Previous meta-analyses have also suggested a significant association between night shift work and the risk of metabolic syndrome and a positive dose-response relationship with the duration of exposure [20]. In this study, unexpected results were observed among shift workers who are inevitably exposed to lifestyles that disrupt circadian rhythm, contrary to expectations. A negative correlation with the risk of metabolic syndrome was observed between night-shift work and other types of shifts, whereas no significant correlation was found in the case of evening-shift work. Several previous studies investigating the relationship between shift work and metabolic syndrome have yielded inconsistent findings [21]. Specifically, a study using KNHANES data did not confirm an association between metabolic syndrome and shift work in men [22]. The lack of a significant correlation between night shift work and metabolic syndrome in this study may be attributed to the cross-sectional research design and the use of nonpurposive data in previous studies. The data used in the current study did not include specific information about the duration of participants’ engagement in the same work pattern or the frequency of changes in their work schedules. Consequently, the impact of long-term engagement in shift work on the development of metabolic syndrome could not be fully assessed. If a person who worked at night quit or changed their work hours because of poor health, the results might have been affected. Additionally, healthy workers tend to endure challenging work environments for longer periods, which might have influenced the results. Shift workers tend to sleep and eat outside of the normal light and dark cycle, and this lifestyle is out-of-phase with the central clock, causing circadian misalignment [23]. Circadian misalignment in shift workers is associated with impaired glucose control and increased inflammatory markers. Long-term circadian misalignment exposure increases the risk of obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease, and stroke [24]. In the late evening, food intake occurs when leptin levels, which help to promote satiety, are lower than during normal eating times, leading to overeating of high-fat and calorie-dense foods and reduced insulin sensitivity [25]. Misaligned sleep may alter the composition of the gut microbiome, while misaligned eating disturbs its rhythmic expression, contributing to insulin resistance, inflammation, and adiposity [26]. Shift work, including night shifts, can cause nocturnal melatonin suppression, which might induce insulin resistance and glucose intolerance, potentially leading to obesity [27]. Circadian misalignment can also lead to the loss of cortisol rhythmicity, and long-term elevated cortisol levels can contribute to the development of components of the metabolic syndrome [28].
The fourth factor is physical activity. Physical activity acts as a synchronizing signal for circadian rhythm and can significantly impact the prevention and management of metabolic diseases in individuals [11]. Engaging in physical activity significantly affects skeletal muscle metabolism, and it is evident that skeletal muscle has a strong circadian profile [5]. There is evidence that exercise can affect the circadian rhythm, as previous studies have shown that physical activity can phase-shift melatonin, thyroid-stimulating hormone, and body temperature [29]. Proper physical activity can be a useful treatment tool for improving poor sleeping patterns, providing a significant circadian phase-shifting effect for individuals with delayed or early-phased sleep disorders, or those who work shifts [5]. In particular, physical activity during the day exposes individuals to brighter ambient light and is accompanied by an increase in body temperature, which can amplify circadian rhythm, foster circadian alignment, and contribute to maintaining a healthy circadian diet [30]. Synchronizing exercise and nutrient interventions to the molecular circadian clock might maximize the health-promoting benefits of exercise in preventing and treating metabolic diseases [5].
Nevertheless, this study has several limitations. First, it was based on cross-sectional data, making it difficult to establish a causal association between circadian rhythm-disturbing factors and metabolic syndrome. Second, circadian rhythm-disturbing factors were evaluated using a questionnaire that relied on the participants’ responses, which could introduce bias and may not have been entirely accurate. Third, the circadian rhythm-disturbing factors that had been investigated lack external validation as they have not been previously established; rather, they were merely aggregated. Previous studies on this topic have rarely validated circadian rhythm-disturbing factors. Additionally, no studies have identified the mechanisms by which two or more circadian rhythm-disturbing factors affect metabolic syndrome. Therefore, further investigations are warranted. Despite these limitations, our study was based on the most recent, nationally representative, community-derived dataset, which is larger than that of most previous studies. We also considered diverse sociodemographic factors, such as household income, marital status, educational background, and health habits. This is the first study to investigate the association between metabolic syndrome and multiple circadian rhythm disturbance factors.
In conclusion, this study revealed a significant association between the number of circadian rhythm-disturbing factors and the risk of metabolic syndrome in Korean adults. The study confirmed that the greater the number of circadian rhythm-disturbing factors, the higher the prevalence of metabolic syndrome. Lifestyles habits that do not disturb the circadian rhythm, such as getting enough sleep, having a regular breakfast, and engaging in physical activity, are potentially powerful tools that can contribute to the prevention of metabolic diseases.
Notes
CONFLICT OF INTEREST
No potential conflict of interest relevant to this article was reported.