Relationship between sleep duration and the metabolic syndrome: Korean National Health and Nutrition Survey 2001

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1 (2008) 32, & 2008 Macmillan Publishers Limited All rights reserved /08 $ ORIGINAL ARTICLE Relationship between sleep duration and the metabolic syndrome: Korean National Health and Nutrition Survey 2001 KM Choi 1, JS Lee 2, HS Park 3, SH Baik 1, DS Choi 1 and SM Kim 4 1 Department of Internal Medicine, Division of Endocrinology and Metabolism, Department, College of Medicine, Korea University, Seoul, South Korea; 2 Division of Biostatistics, Graduate School of Public Health Department, College of Medicine, Korea University, Seoul, South Korea; 3 Department of Family Medicine, University of Ulsan College of Medicine, Seoul, South Korea and 4 Department of Family Medicine, College of Medicine, Korea University, Seoul, South Korea Objectives: Previous studies have revealed that both short and long sleep durations are linked to obesity, hyperglycemia and hypertension. We evaluate the relationship between sleep duration and the metabolic syndrome using representative national survey data from the Korean population. Methods: We analyzed data from the 2001 Korean National Health and Nutrition Survey. The average amount of sleep per night was categorized as: p5, 6, 7, 8 and X9 h. Those reporting 7 h per night served as a reference group. In this cross-sectional study, the data of 4222 participants were finally analyzed. Results: A majority of the components of the metabolic syndrome demonstrated U-shaped patterns based on sleep duration. Although the prevalences of abdominal obesity and hypertension were highest in subjects who slept p5 h per night, those of hyperglycemia and high triglyceridemia were highest in subjects who slept X9 h per night. Prevalence of the metabolic syndrome also exhibited U-shape pattern based on sleep duration. More components of the metabolic syndrome were highly associated with sleep duration in subjects under the age of 60 compared to those over the age of 60. Subjects who slept p5h per night demonstrated the highest risk for the metabolic syndrome (OR 1.74, 95% CI , Po0.001). Subjects who slept X9 h per night exhibited increased risk for the metabolic syndrome even after adjustment of other risk variables (OR 1.69, 95% CI , P ¼ 0.006). Conclusions: Both short and long sleep durations are related to increased risk of the metabolic syndrome and its components in the Korean population, although adjustment for risk factors attenuates their relationship. Subjects reporting sleep duration of 7 h demonstrated the lowest prevalence of the metabolic syndrome. (2008) 32, ; doi: /ijo ; published online 13 May 2008 Keywords: metabolic syndrome; sleep duration; hypertension; Korean National Health and Nutrition Survey Introduction Sleep loss due to self-imposed bedtime restriction has become a common phenomenon in modern society. 1 Previous studies have indicated that short sleep duration is associated with elevated body mass index (BMI). 2,3 In a recent prospective study, Hasler et al. 4 determined a longitudinal relationship between short sleep duration and future weight gain. Additionally, evidences from laboratory and Correspondence: Dr SM Kim, Department of Family Medicine, Graduate School of Public Health Department, College of Medicine, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul , Korea. ksmpdh@korea.ac.kr Received 18 September 2007; revised 23 March 2008; accepted 24 March 2008; published online 13 May 2008 epidemiological studies have indicated that insufficient sleep may result in decreased glucose tolerance and increased risk for type 2 diabetes. 5,6 Decreased insulin sensitivity has been observed with different lengths of sleep deprivation. 7 Furthermore, a recent epidemiological study demonstrated an increased risk of hypertension incidence with short sleep duration, even after controlling for obesity and diabetes. 8 Sleep deprivation studies have shown significant increases in blood pressure and sympathetic nervous system activity in both normotensive and hypertensive subjects. 9,10 Altogether, the data suggest that sleep duration may be an important risk factor for the metabolic syndrome. Although scanty previous reports showed an association between sleep duration and several components of the metabolic syndrome, 11 to our knowledge, there are no previous reports on a direct relationship between sleep duration and the

2 1092 metabolic syndrome. Furthermore, most previous studies on sleep duration and components of the metabolic syndrome have been based on a Caucasian population. In the present study, we have examined the relationship between sleep duration and the metabolic syndrome using representative data from the Korean population. Subjects and methods Study subjects The Korean National Health and Nutrition Survey (KNHNS) was performed by the Korean Ministry of Health and Welfare. The 2001 KNHNS was a cross-sectional and nationally representative survey, the details of which have been previously published. 12,13 A stratified multistage probability sampling design was used, with selections made from sampling units based on geographical area, sex, and age based on household registries. There were primary sampling units, each of which contained approximately 60 households. Two hundred sampling frames ( households) from primary sampling units were randomly selected throughout South Korea. The survey was completed by 9770 of individuals who participated in the Health Examination Study, resulting in a participation rate of 77.3%. After exclusion of participants under 20 years of age (n ¼ 3169), we utilized data collected from 6601 subjects over 20 years of age for this study. The diagnostic criteria of the metabolic syndrome in children were different from those used for adults, and previous studies showed extreme heterogeneity for the sets of variables and cutoff values. Therefore, we excluded subjects under 20 years of age in the present study. Among the 6601 participants, those without fasting time data (n ¼ 236), those who did not fast for a long enough period of time (n ¼ 1253), and those without sleep duration data (n ¼ 342) were excluded. Then, we further excluded subjects who were taking medications to treat the metabolic syndrome (n ¼ 548), resulting in a total final sample size of 4222 subjects (1822 men, 2400 women) for analysis. Excluded subjects were more likely to have higher age (48.1±0.5 for excluded vs 44.1±0.4 for included), have higher waist circumference (82.5±0.3 cm for excluded vs 80.3±0.2 cm for included), have higher BMI (23.8±0.1 for excluded vs 23.3±0.1 for included), have higher systolic (126.2±0.7 mm Hg for excluded vs 120.9±0.5 mm Hg for included) and diastolic blood pressure (78.6±0.4 mm Hg for excluded vs 76.6±0.3 mm Hg for included). However, gender distribution was similar (men 44.3% for excluded vs 43.2% for included). Each respondent was assigned a weight, based on geographic and demographic characteristics, to allow findings to be extrapolated for the entire Korean population. Nurses were trained to carry out anthropometric measurements, serum collection, blood pressure measurements and questionnaires management. The questionnaires included items concerning the demographic, socioeconomic, dietary and medical history details of each respondent. Self-reported alcohol intake, smoking and physical exercise were estimated from the questionnaire. Alcohol consumption was categorized based on the usual frequency and intake of alcoholic beverages. The categories are as follows: none, X1 cup once a week, X5 cups in men or X4 cups in women 1 2 times a week and X5 cups in men or X4 cups in women three times a week or more. 14 This quantity-frequency method is based on the guideline of WHO (World Health Organization) and modification of the Korean Ministry of Health and Welfare. 15 In the survey, individuals were classified as nonsmokers, ex-smokers or current smokers. Physical exercise was defined according to estimated energy consumption per week. Categories included: none, o7.5, and 415 kcal kg 1 per week. 14 Using the definition by the Korean government, small towns and villages with a population of p were designated as rural areas. 16 A family history of hypertension or diabetes was considered positive if at least one of the parents or one sibling had diabetes or hypertension. Anthrophometric and laboratory measurement Body weight and height were measured with subjects wearing light clothing and no shoes. BMI was calculated as weight (in kg) divided by height (in m 2 ). Waist circumference was measured from the narrowest point between the lower borders of the rib cage and the iliac crest. Blood pressure was measured in a sitting position after a 10-min rest period. Two systolic and diastolic blood pressure readings were recorded with a 5-min interval and averaged for analysis. Fasting blood sample was taken in the morning following at least an 8-h fast. Blood samples were centrifuged, refrigerated at the examination site and transferred in ice boxes to a central laboratory in Seoul on the same day samples were taken. Plasma glucose, total cholesterol, triglyceride and high-density lipoprotein (HDL)-cholesterol were measured using an auto-analyzer (Hitachi 747 autoanalyzer, Tokyo, Japan). Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation for subjects with serum triglyceride levels p400 mg per 100 ml. 17 Definition of the metabolic syndrome We defined subjects as having the metabolic syndrome who had three or more of the following criteria as defined by the National Cholesterol Education Program: 18,19 (1) central obesity; (2) hypertriglyceridemia with fasting plasma triglycerides X1.69 mmol l 1 (150 mg per 100 ml); (3) low HDL cholesterol with fasting HDL cholesterol o1.04 mmol l 1 (40 mg per 100 ml) in men and o1.29 mmol l 1 (50 mg per 100 ml) in women; (4) hypertension with systolic or diastolic blood pressurex130/85 mm Hg and (5) hyperglycemia with fasting plasma glucose X5.6 mmol l 1 (100 mg per 100 ml). To define central obesity, we used the Asia-Pacific criteria for

3 obesity based on waist circumference as defined by WHO. 20 Specifically, the waist circumference threshold for central obesity is X90 cm in men and X80 cm in women. Statistical analysis All statistical analyses were performed using SUDAAN release 8.0 (Research Triangle Institute, Research Triangle Park, NC, USA) to reflect the characteristics of the study s multistage sampling design. The age-adjusted prevalence of each component or cluster of the metabolic syndrome components were calculated using a direct adjustment method, presented as % and 95% confidence interval (CI). The 2001 National Census data from the Korea National Statistical Office was used to define the standard population. Survey weights were used to calculate standard errors in prevalence rates. Crude and adjusted ORs for the metabolic syndrome were obtained using multiple logistic regression analysis and adjusting for age, gender, family history of hypertension or diabetes, residential area, education level, monthly income, alcohol, smoking and exercise according to each model. Results Table 1 summarizes the characteristics of study population according to self-reported sleep duration. Cardiovascular risk variables such as waist circumference, blood pressure and fasting lipid profiles exhibited a trend of U-shape pattern. The post-hoc analysis showed that in most of the cardiovascular disease (CVD) risk factors the main significant difference is between people who slept o5 h and those who slept 7 h. Subjects reporting 7 h of sleep per night demonstrated the least propensity for these risk variables, although they had the highest family history of hypertension or diabetes. In Table 2, prevalences and 95% CIs of the metabolic syndrome components classified by sleep duration are shown. Subjects reporting sleep duration of 7 h exhibited the lowest prevalence of any components of the metabolic syndrome except low HDL cholesterol. Although the prevalences of abdominal obesity and hypertension were highest in subjects who slept p5 h per night, those of hyperglycemia and high triglyceridemia were highest in subjects who slept X9 h per night. The prevalence of the metabolic syndrome also exhibited U-shape pattern based on sleep duration. Subjects reporting sleep duration of 7 h demonstrated the lowest prevalence of the metabolic syndrome. Table 3 shows the prevalence of the metabolic syndrome components classified by sleep duration in younger and elderly subjects. The parameters that significantly differ by sleep duration for younger subjects did not appreciably differ for older subjects. The parameters that approached being significantly different by sleep duration for older subjects did not appreciably differ for younger subjects. More components of the metabolic syndrome were highly associated with sleep duration in subjects under the age of 60 compared to those over the age of 60. We calculated ORs and 95% CIs using multiple logistic regression analyses for the metabolic syndrome classified according to sleep duration (Table 4). With those reporting sleep duration of 7 h serving as the reference group, both short and long sleep durations were linked to an increased risk for the metabolic syndrome in an unadjusted model. Subjects who slept p5 h per night were at the greatest risk for the metabolic syndrome (OR 1.74, 95% CI , Po0.001). Even after adjustment for age, gender, BMI, family 1093 Table 1 Clinical and biochemical characteristics classified by sleep duration Sleep duration (hour per day) P z p X9 Age (years) 51.3±0.9 abcd 45.0±0.6 aef 41.8±0.5 be 42.5±0.6 cf 43.5±1.2 d o0.001 Waist circumference (cm) 81.4±0.4 a 80.5± ±0.3 a 80.4± ± Body mass index 23.6± ± ± ± ± Systolic BP (mm Hg) 124.6±1.1 abc 121.5±0.7 ad 118.6±0.8 bdef 120.8±0.7 ce 122.0±1.2 f o0.001 Diastolic BP (mm Hg) 77.6±0.7 a 77.2±0.4 b 75.4±0.4 abc 77.0±0.5 c 76.3± FBG (mmol l 1 ) 5.35± ± ± ± ± Total cholesterol (mmol l 1 ) 4.96± ± ± ± ± HDL cholesterol (mmol l 1 ) 1.19± ± ± ± ± LDL cholesterol (mmol l 1 ) 3.05±0.04 abc 2.95±0.03 a 2.91±0.03 b 2.93±0.03 c 2.95± Triglyceride (mmol l 1 ) 1.52± ± ± ± ± Monthly income a, n (%) o0.001 p (16.1) 316 (28.9) 260 (23.0) 271 (23.9) 96 (8.0) (10.4) 446 (25.0) 536 (30.4) 454 (26.7) 126 (7.5) (11.2) 203 (25.0) 248 (33.1) 170 (24.4) 45 (5.4) X (10.1) 119 (29.0) 131 (33.8) 86 (21.6) 17 (5.6) Abbreviations: BP, blood pressure; FBG, fasting blood glucose; HDL, high-density lipoprotein; LDL, low-density lipoprotein. Demographic characteristics are presented as the mean±s.d. or as numbers and percentages, as appropriate. z P-values were calculated using ANOVA test or w 2 -test. a,b,c,d,e,f Significant difference based on linear contrasts multiple comparisons. Units are Korean won per month.

4 1094 Table 2 Prevalence (95% confidence interval) of the metabolic syndrome components classified by sleep duration p5h 6h 7h 8h X9h P a Elevated blood glucose 32.4 ( ) 34.1 ( ) 30.9 ( ) 35.7 ( ) 35.9 ( ) Abdominal obesity 41.4 ( ) 31.5 ( ) 29.2 ( ) 32.1 ( ) 34.5 ( ) Elevated blood pressure 42.7 ( ) 33.2 ( ) 25.9 ( ) 32.4 ( ) 33.3 ( ) o0.001 High triglyceride 29.4 ( ) 31.9 ( ) 27.8 ( ) 32.5 ( ) 34.3 ( ) Low HDL cholesterol 54.2 ( ) 50.4 ( ) 50.2 ( ) 46.8 ( ) 53.9 ( ) Number of components of the metabolic syndrome ( ) 18.5 ( ) 20.5 ( ) 19.1 ( ) 17.4 ( ) X ( ) 81.5 ( ) 79.5 ( ) 80.9 ( ) 82.6 ( ) X ( ) 52.9 ( ) 48.6 ( ) 53.3 ( ) 57.5 ( ) o0.001 X ( ) 27.7 ( ) 23.2 ( ) 27.7 ( ) 31.8 ( ) o0.001 X ( ) 11.3 ( ) 8.5 ( ) 9.8 ( ) 9.9 ( ) ( ) 2.7 ( ) 1.2 ( ) 2.5 ( ) 3.1 ( ) Abbreviation: HDL, high-density lipoprotein. a P-values were calculated using w 2 -test. Table 3 Prevalence (95% confidence interval) of the metabolic syndrome components classified by sleep duration in younger and elderly subjects p5h 6h 7h 8h X9h P a Age o60 Elevated blood glucose 32.7 ( ) 33.1 ( ) 31.5 ( ) 35.1 ( ) 33.6 ( ) Abdominal obesity 37.9 ( ) 27.4 ( ) 27.2 ( ) 30.4 ( ) 32.3 ( ) Elevated blood pressure 34.5 ( ) 27.1 ( ) 21.8 ( ) 27.6 ( ) 23.5 ( ) High triglyceride 26.4 ( ) 29.6 ( ) 25.0 ( ) 31.2 ( ) 33.4 ( ) Low HDL cholesterol 49.9 ( ) 48.5 ( ) 49.5 ( ) 46.2 ( ) 49.5 ( ) Number of components of the metabolic syndrome ( ) 21.0 ( ) 22.1 ( ) 20.7 ( ) 20.5 ( ) X ( ) 79.0 ( ) 77.9 ( ) 79.3 ( ) 79.5 ( ) X ( ) 48.1 ( ) 46.2 ( ) 51.0 ( ) 52.8 ( ) X ( ) 23.4 ( ) 20.9 ( ) 24.8 ( ) 25.7 ( ) X ( ) 9.0 ( ) 6.6 ( ) 8.2 ( ) 6.8 ( ) Age X60 Elevated blood glucose 31.6 ( ) 38.8 ( ) 26.0 ( ) 39.8 ( ) 45.1 ( ) Abdominal obesity 48.9 ( ) 50.2 ( ) 44.6 ( ) 43.0 ( ) 43.2 ( ) Elevated blood pressure 60.0 ( ) 61.0 ( ) 56.9 ( ) 62.5 ( ) 71.5 ( ) High triglyceride 35.7 ( ) 41.9 ( ) 49.4 ( ) 40.5 ( ) 37.7 ( ) Low HDL cholesterol 63.6 ( ) 59.0 ( ) 55.3 ( ) 50.4 ( ) 70.6 ( ) Number of components of the metabolic syndrome ( ) 7.4 ( ) 7.9 ( ) 9.3 ( ) 4.9 ( ) X ( ) 92.6 ( ) 92.1 ( ) 90.7 ( ) 95.1 ( ) X ( ) 74.4 ( ) 66.5 ( ) 67.2 ( ) 75.7 ( ) X ( ) 46.7 ( ) 40.4 ( ) 46.0 ( ) 55.6 ( ) X ( ) 21.3 ( ) 22.8 ( ) 19.7 ( ) 21.7 ( ) Abbreviation: HDL, high-density lipoprotein. a P-values were calculated using w 2 -test. history of hypertension or diabetes, alcohol, smoking, exercise and other risk factors, the relationship between sleep duration and the metabolic syndrome persisted particularly in group reporting 49 h of sleep a night (OR 1.69, 95% CI , P ¼ 0.006). Discussion In the present study, we found a U-shaped association between sleep duration and the metabolic syndrome in the Korean population. In recent years, self-reported sleep duration of Americans has decreased by h over the past 40 years, with many Americans sleeping only 5 6 h per night. 21 According to the 2001 National Sleep Foundation Survey, approximately 31% of Americans sleep 6 or fewer hours per day. 22 In concert with declining sleep duration, there has been an increase in the prevalence of obesity. Short sleep duration has recently drawn attention as a possible cause of obesity. Several epidemiological studies have observed an association between sleep duration and obesity. 2,3,23,24 Taheri et al. 25 and Patel et al. 26 observed a U-shaped relationship between sleep duration and BMI. Furthermore, in a recent longitudinal study, short sleep duration was associated with a

5 Table 4 Odds ratio (95% confidence interval) of the metabolic syndrome based on sleep duration Unadjusted Model 1 a Model 2 b Model 3 c p5 h 1.74 ( ) 1.23 ( ) 1.15 ( ) 1.17 ( ) 6 h 1.27 ( ) 1.13 ( ) 1.11 ( ) 1.07 ( ) 7h h 1.27 ( ) 1.28 ( ) 1.26 ( ) 1.32 ( ) X9 h 1.55 ( ) 1.47 ( ) 1.46 ( ) 1.69 ( ) Subjects were considered to have the metabolic syndrome if they had more than three components according to the definition of National Cholesterol Education Program. a Model 1, adjusted for age, gender and family history of hypertension or diabetes. b Model 2, adjusted for the variables in model 1 plus residential area, education level, monthly income, alcohol, smoking and exercise. c Model 3, adjusted for the variables in model 2 plus BMI. modest increase in future weight gain and incident obesity. 27 In the present study, we confirmed this U-shaped relationship using central obesity criteria based on waist circumference. Participants who slept p5 h per night had the highest prevalence of central obesity. As a mechanism, Taheri et al. 25 demonstrated that short sleep duration was associated with reduced leptin and elevated ghrelin levels, which are known to control appetite and body weight. In a randomized crossover clinical trial, sleep deprivation was linked to reductions in the anorexic hormone leptin, elevations in the orexigenic factor ghrelin and increased hunger and appetite. 28 In long sleepers, reduced energy expenditure due to increased time in bed may affect their obesity, as a study has shown that long sleeper exercise less. 29 Ayas et al. 5 reported that both short and long self-reported sleep durations were associated with an increased risk for developing diabetes. Interestingly, the relative risk of diabetes was attenuated in short sleepers, and disappeared after controlling for BMI. However, in long sleepers, a significant positive association between sleep duration and diabetes persisted even after controlling for BMI. Consistent with previous reports, 5,6 we found U-shaped pattern for hyperglycemia based on sleep duration in the present study. Previous studies have demonstrated that subjects in the sleep-deprived state have impaired glucose tolerance, higher evening cortisol levels, increased sympathetic nervous system activity and a reduction in leptin secretion compared to those in the recovery state. 30 Although mechanisms underlying the association between long sleep duration and diabetes are unclear, chronic subclinical inflammation associated with visceral obesity may trigger long sleep duration and hyperglycemia due to the sleep-inducing 31 and metabolic 32 effects of pro-inflammatory cytokines, including interleukin-1 and tumor necrosis factor-a. Blood pressure gradually falls with the onset of sleep, and promptly rises after awakening. 33 After nights where sleep was restricted to h, significant increases in blood pressure and sympathetic nervous activity were reported. 10 Habitually short sleep durations may lead to the development and persistence of hypertension through longer exposure to daytime stress and elevated sympathetic system activity. 8 Recently, Gangwisch et al. 8 found an association between short sleep duration and the incidence of hypertension in middle-aged subjects and found no relationship in elderly subjects. Another study confirmed this result in the elderly. 34 In the present study, we observed that subjects who slept p5 h per night exhibited the highest prevalence of hypertension, with U-shaped pattern for hypertension based on sleep duration. This association was found only in younger subjects, which is consistent with previous studies. Metabolic syndrome represents a cluster of several metabolic risk factors that are linked to an increase in CVD. the metabolic syndrome results in an approximate twofold increase in the relative risk for cardiovascular events compared to subjects without the syndrome. 35 Recently, short and long self-reported sleep duration was reported to be associated with a modestly increased risk of coronary events in women. 29 In a prospective study, sleeping o6h or 47 h a night was associated with increased mortality following adjustment for other risk factors. 26 Our results may provide a mechanism linking sleep duration and mortality via mediation of the metabolic syndrome. In the present study, subjects reporting 7 h of sleep per night showed the lowest prevalence for the metabolic syndrome, which is compatible with the previous report s finding that mortality risk was lowest among women reporting sleep duration of 7 h. 26 The results of our study showed U-shaped pattern of prevalence for the metabolic syndrome based on sleep duration in an unadjusted model. We found the attenuation in the relationship between short sleep duration and the metabolic syndrome after adjustment of other variables. The demographic variable indicative of low socio-economic status (SES) may account for this. The relationship between poor health outcomes and low SES has been hypothesized to be due in part to short sleep duration among this group. 36 The present study showed that the association of the metabolic syndrome components and sleep duration were different between younger and elderly subjects. It is compatible with previous studies that reported no relationship between sleep duration and obesity in elderly adults. 24,27 We performed both weighted and unweighted analyses in the present study and found no appreciable differences in the results between the two. We chose to show the weighted results, because those reflect the characteristics of the study s multistage sampling design. There are some limitations in our study. First, self-reported sleep duration was used in our analyses rather than actual measurement of sleep duration. However, good correlations have been reported in previous studies between self-reported sleep duration and values obtained through actigraphic monitoring. 37 Due to the nature of the present study, which used national epidemiological survey data, it would be impractical to measure sleep duration. Second, the crosssectional design precludes defining causal relationships. 1095

6 1096 Third, different components of the metabolic syndrome are risk factors for each other. Nevertheless, this study had its own advantages using KNHNS data, as it ensured reliable countrywide sampling and utilized a survey that was both large-scale and nationally representative. Furthermore, the present study analyzed the relationship between sleep duration and the metabolic syndrome after adjustment of various potential risk factors for the metabolic syndrome. Conclusion These national survey data indicate that both short and long sleep durations are associated with an increased risk for the metabolic syndrome and its components in the Korean population, although adjustment for risk factors attenuates their relationship. Sleep duration might be a potential risk factor for the metabolic syndrome. Acknowledgements We thank the members of the Korea Institute for Health and Social Affairs who conducted the national survey. 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