Does long sleep duration increase risk of metabolic syndrome in Azar cohort study population?

Background: We decided to assess the correlation between metabolic syndrome (MetS) risks,sleep and napping duration in Azar cohort population according to the increasing incidence of MetS in the world and inconsistence results about sleep duration and MetS. Methods: In this cross-sectional study, MetS and sleep habits of 14916 subjects (35-70 years old) who inhabited in Shabestar city were determined by ATPIII and Pittsburg questionnaire respectively. Inclusion criteria were subjects with 35-70 years old and living in Shabestar for at least 9 months of the year. Results: According to the results, age, living place, body mass index, hypnotic drug use, sleep and napping duration and TV time were the risk factors of MetS. In this regard, long sleep duration (>9 h/24 h), napping (0.25-2 h/day), hypnotic drug use and watching TV (2 h/day)increased the risk of MetS by 1.18 (1.05-1.33), 1.16(1.07-1.26), 1.35(1.13-1.60), and 1.13(1.04-1.23) respectively. Conclusion: According to these results, it appears that proper education for improvement of sleep habit is necessary to reduce incidence of MetS and its consequences. However, there is need for more longitudinal researches and using objective method of sleep habits evaluation for more precise results.


Introduction
Metabolic syndrome (MetS) includes a set of abnormalities such as hypertension, dyslipidemia, impaired glucose tolerance and abdominal obesity. 1 According to the results of recent studies, prevalence of MetS along with obesity is increasing in the world especially in developing countries that may be due to the changes in life styles and food habit. It is estimated that about a quarter of the world population has MetS. 2 Traditionally, obesity and sedation life style are considered as the main contributors of the MetS development. 3 Nowadays, other new factors such as socioeconomic status 4 and sleep duration, 5 have been proposed as risk factors in metabolic syndrome development.
Recently , Koren and Taveras noted that sleep deprivation and long sleep duration are associated with increasing the risk of central obesity, metabolic syndrome, cardiovascular diseases and mortality. 5 While, recent systematic review and meta-analysis studies revealed that the relationship between sleep duration and MetS are inconsistence. [6][7][8] In this regard, Xi et al reported no significant relationship between long sleep duration and MetS. 7 Moreover, Iftikhar et al could not confirm a significant correlation between long sleep duration and metabolic syndrome. 6 Well designed studies with large sample size are needed to clarify the relationship between sleep duration and MetS on the basis of aforementioned studies.
Considering the increasing incidence of MetS in the world and inconsistent results about the associations between sleep duration and MetS, we decided to assess the correlations between MetS risks, sleep and napping duration in Azar cohort population.

Participants and procedures
This cross-sectional study was approved by Ethics Committee of Tabriz University of Medical Sciences. We used a part of Azar's cohort study data in this study.
All eligible individuals from 35 up to 70 years old in Shabestar region were invited to participate in the study from October 2014 to January 2017, and those who were signed the consent form are included in the Azar cohort study. Those included the inhabitants in Shabestar for at least 9 months. The participants with severe psychiatric or physical illness, body mass index (BMI) <18.5 kg/ m 2 , and pregnant women were excluded from the study. The pilot and enrolment phase recruited further 15 006 participants, giving 16 138 in total. The overall response rate of those invited was equal to 93%. We included 14 916 subjects on the basis of inclusion criteria of the present study. Demographic information of participants was collected by questionnaire including age, gender, marital status, education level, etc. Blood samples were collected after an overnight fast of 12 hours. Fasting blood sugar (FBS), serum triglyceride (TG), high density lipoprotein (HDL) were determined by enzymatic method.
Moreover, height, weight, waist circumference and blood pressure of participants were measured. The method of measurements of mentioned factors has been explained in previously published article 9 with more details. Women with waist circumference ≥88 cm and men with waist circumference of ≥102 cm were considered as abdominally obese. 10 Subjects with SBP ≥130 and DBP ≥85 or antihypertensive drug treatment in a patient with a history of hypertension is an alternate indicator considered as patients with hypertension. 11

Study area
Azar cohort study is a part of a large Persian cohort study (The Prospective Epidemiological Research Studies of the Iranian Adults) 9,12 which was launched at October 2014 and finished at January 2017. Azar cohort was established in Shabestar in East Azarbaijan province (North-west of Iran). It is conducted in 3 phases of pilot, enrollment and follow-up.
Shabestar is the capital of Shabestar city, East Azerbaijan province, Iran. At the 2011 census, its population was equal to 25 663, with 4824 families. It is located in proximity to Tabriz, the provincial capital, on the main Iranian-International railway line which connects Tehran and Tabriz to Turkey and Europe. Considering the proximity to Lake Urmia, the city experiences mild weather with wet winters, and summers are somewhat hot and dry during day time and cooler at night.

Socioeconomic status
Socioeconomic status (SES) was defined based on job categories, education levels, and the family assets by using principal component analysis (PCA). SES classified into very high, high, middle, low and very low based on quintuple of obtained scores.

Metabolic syndrome definition
We defined metabolic syndrome according to the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII) criteria. 13 Subjects with 3 or more, the following conditions were defined as having the MetS: Waist circumference ≥102 cm in men and ≥88 cm in women, TG ≥150 mg/dL (drug treatment for elevated TGs is an alternate indicator), HDL-C <40 mg/dL in men and <50 mg/dL in women. Elevated blood pressure systolic ≥130 and/or diastolic ≥85 mm Hg (antihypertensive drug treatment in a patient with a history of hypertension is an alternate indicator). Elevated fasting glucose ≥100 (drug treatment of elevated glucose is an alternate indicator).

Sleep habits
Sleep habits of population were assessed using Pittsburgh questionnaire. Sleep habits information were presented in 3 forms: 24 hours sleep duration which was a sum of nocturnal and day time sleep hours, night sleep duration showed sleep duration at night and day time napping indicated sleep duration in day. Total sleep duration and night sleep duration was classified into 3 groups: <6 hours, 6-9 hours, and >9 hours. In addition, day time napping was categorized to: subjects, who were not napped, 0.25-2 hours, and >2 hours.

Statistical analysis
Data were reported as mean, ± SD and also number (percent) where applicable. Comparisons were done using χ 2 test for the categorical variables between groups (education level, marital status, etc). We used backward logistic regression analysis for estimating adjusted odds ratios (ORs) and their corresponding 95% CI. 6-9 hours' sleep was considered as reference group in all analyses and those who not napped was considered as reference group in day time napping. Moreover, those who watched TV less than 2 hours and those who not have night shift work were determined as reference group. Data analysis was performed with SPSS Statistics for Windows version 21.0 (IBM Inc., Armonk, NY, USA) and the level of significance was set at 0.05. Table 1, among 14 916 participants, 5104 (34.22%; 95% CI: 33.44% to 34.96%) had MetS which was higher in women rather than men (41.0% vs. 25.8%). The prevalence of MetS among illiterates, those who divorced and those lived in rural area was significantly more than other groups (P < 0.001). Moreover, the prevalence of MetS in low and very low SES classification was significantly higher than other classifications (P < 0.001). Our findings indicated that MetS was more prevalent in those who

Discussion
Nowadays, prevalence of MetS parallel is increasing worldwide by increase in obesity. So, it can be considered as a silent killer. Moreover, sleep disturbance becomes a common problem in recent years. 14 On the other hand, it has been known that sleep duration plays an important role in maintaining a good health. 5 In this regard, U shaped association has been reported between sleep duration and increased risk of mortality. 15,16 The results of this cross-sectional study with large sample size showed that long sleep duration were significantly increased the risk of MetS which is consistence with Jike et al's study. They reported that sleep more than 8-9 h/day are significantly associated with cardiovascular disease and mortality. 17 The findings of another study indicated that short and long sleep duration increased the risk of metabolic syndrome. 8 In contrast to our results, previous studies reported that there is a positive correlation between short sleep duration (<6 h) and MetS components. 7,18,19 the discrepancy between our results and other studies may be due to the self-report sleep and different definitions of short or long sleep duration.
Also, we found that, day time napping increased the risk of MetS. In line with these results, Guo et al observed that day time napping over 1 hour increased the risk of type II diabetes. 20 In a cohort study on retired worker indicated that long afternoon napping can be considered as a novel risk factor of Type II diabetes. In another population based study, Lin et al reported that napping increased the risk of MetS in non-obese Chinese women. 21 Yang et al found that long duration of napping was positively associated with MetS incidence. 22 By these mechanisms, long duration of napping which increased the risk of MetS has not been fully understood. On the basis of previous studies, some mechanisms have been proposed for this association. Long duration napping reduced energy expenditure which is linked with obesity and its consequences. Moreover, it has been reported that disrupting of circadian rhythm involved in insulin resistance and diabetes mellitus. On the other hand, evening cortisol concentration elevated in the nap takers, that lead to subjects become predisposed to insulin resistance. After adjusting the confounder factors, those who watched TV more than 2 hours had 13% (OR 1.13; 1.04-1.23) more risk of MetS compared to those watched ≤2 hours. Of course, it should be noted the observed significance in narrow OR may be due to large sample size. These results are in line with previous studies which conducted on leisure time and cardiometabolic risk factors. Rosique-Esteban et al observed that long watching TV increased the risk of obesity, type II diabetes and metabolic syndrome components. 23 Results of another study indicated that less physical activity and more watching TV are significantly associated with MetS. 24 In the present study, those who used hypnotic drugs had 35% (OR: 1.35; 1.13-1.60) more risk for metabolic syndrome compared to those who did not use. This finding is supported by previous study which showed there is a positive correlation between hypnotic drug use and MetS. 25 The precise mechanism of how hypnotic drug leads to increase in the risk of MetS is not known. It has been assumed that these drugs change life style by reducing physical activity. 26 Moreover, most subjects who use hypnotic drugs have other psychiatric problems such as depression 27 which may increase the risk of MetS. 24 The results of the present study should be interpreted considering the following limitations: (1) the crosssectional design of the study, which implies that no causal inferences could be made. (2) Using subjective measurements of sleep pattern that may be a potential for misreporting. The strength of this study is the assessment of sleep habits and MetS components in large population.

Conclusion
The findings of present study showed that long sleep duration and napping in 24 hours increased the risk of MetS. Moreover, we found that watching TV more than 2 h/day is significantly associated with MetS. According to these results, it appears that proper education for improvement of sleep habit is necessary to reduce incidence of MetS and its consequences. However, for more precise results, there is need to more longitudinal researches and using objective method of sleep habits evaluation.

Ethical approval
This study was approved by Ethics Committee of Tabriz University of medical sciences (TBZMED.REC.1393.205). After a full explanation of the study was provided, and prior to commencing participation, all participants provided written informed consent.

Competing interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding
Liver and gastrointestinal diseases research center, Tabriz University of Medical Sciences.

Authors' contributions
Conception and design: MHS. Doing the field, experimental, clinical, data collection or compilation work, provided there is also a scholarly input during the process: EF. Data analysis and interpretation: EF, ZN. Preparation of draft manuscript, doing revisions or providing critique: ZN, EF, ARO. Overall and/or sectional scientific management: MHS.