The results of the updated HEXA-G (2004–2013) analysis on sleep duration and metabolic syndrome and its components confirm and further expand on the previously published HEXA study (2004–2008) [13], displaying findings not shown in prior studies. In the previous HEXA study [13], after adjusting for covariates, 10 h sleep or greater was associated with MetS in women only (OR: 1.53, 95% CI: 1.32–1.78 for women; OR: 1.19, 95% CI: 0.98–1.46 for men); while, less than 6 h sleep was not associated with MetS in both men and women (OR: 1.09, 95% CI: 0.99–1.19; OR: 1.04, 95% CI: 0.97–1.11 respectively). However, in the current study, with expanded sample size and power, a positive association was observed between 10 h sleep or greater and MetS in both men and women (OR: 1.28, 95% CI: 1.08–1.50; OR: 1.40, 95% CI: 1.24–1.58 respectively) as well as in less than 6 h sleep among men (OR: 1.12, 95% CI: 1.05–1.19). In the supplemental analysis, a similar J-shape trend existed but with a significant positive association between 10 h sleep or greater and MetS only in women; between 5 h sleep and MetS only in men. Gender interaction in the association between sleep duration and metabolic syndrome was statistically significant in our study which complements the gender difference reported in a study looking at the association between sleep duration and mortality [20]. While the exact mechanisms are unclear, one explanation may be that women experiencing menopausal transition face erratic fluctuations and eventual decline in estrogens as well as ovarian oestradiol which may lead to frequent sleep disruptions [21, 22], a common characteristic of long sleep duration [23]. Another study posits that women may have shorter circadian period contributing to higher prevalence of insomnia and/or perception of less restorative sleep [24]. Additionally, a study examining the association between inflammatory markers and sleep duration observed higher levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in women who slept less than 5 h or more than 9 h, while no significant marker variation was observed in men [25]. Notably, a recent meta-analysis stated that women may be more vulnerable to the effects of sleep disturbance and displayed greater increases of CRP and IL-6 compared with men. The review also reported that long sleep duration, but not short duration was associated with increases in CRP and IL-6 [26].

Few studies have reported gender-stratified sleep association with MetS. A meta-analysis of 12 cross-sectional and 3 cohort studies from North America, Europe, and Asia, has found that both less than 5 h and greater than 8 h sleep duration were associated with MetS but reported no gender differences between the association [27]. Additionally, a study in Korea reported that both short (less than or equal to 5 h) and long (greater than or equal to 9 h) sleep are related to increased risk of MetS, however, with gender adjusted [28]. Other studies broadly categorized hours of sleep into “short” and “long” and did not report the association between hour-specific sleep duration and MetS. For example, one cross-sectional study conducted in China categorized sleep duration into 2- h intervals and found that both short (less than 6 h) and long (greater than 9 h) sleep was associated with MetS in males only [29]. Similarly, a prospective study conducted in Korea has also used 2-h sleep intervals and reported that only short (less than 6 h) sleep was associated with MetS in a mixed gender population [30]. Furthermore, while a recent meta-analysis reported that a dose-response relationship exists between short sleep and MetS, it did not support the notion that long sleep is associated with MetS [31]. The opposite was observed in a study conducted in Korea in which greater than or equal to 9 h was associated with MetS but not with sleep less than or equal to 5 h [32].

Although the biological mechanism of sleep duration and MetS remains unclear, several potential endocrinologic, immunologic, and metabolic processes have been reported. Sleeping less than 7 h may cause reciprocal changes in circulating levels of leptin and ghrelin [33] which would increase appetite, caloric intake, reduce energy expenditure [34] facilitating an increase in waist circumference as well as overall obesity development. It may also cause impaired glycemic control (lowering glucose tolerance and thyrotropin concentration levels) increasing risk for hypertension and diabetes [35]. Other endocrinologic effects include increased cortisol levels which may elevate fasting glucose levels [36]. Additionally, clinical studies have shown that sleep deprivation results in increased levels of high-sensitivity CRP and IL-6 during, markers that have also been associated with constituents of MetS [37].

Likewise, number of studies report detrimental health effects of long sleep [27, 38] and suggest sleeping in moderation (approximately 7 h) rather than in abundance for optimum health [39]. Potential effects of long sleep include: increased sleep fragmentation with lower sleep quality [23], greater fatigue [40], limited photoperiod and greater physiological deprivation (i.e. exercise) [23]. All of these conditions are studied to be associated with insulin resistance, dyslipidemia and hormonal imbalance [41] which may lead to premature death [23, 39].

While the current study displays a correlation between sleep duration and MetS, there are a couple factors to consider. First, the current study is cross-sectional and therefore, causality between sleep duration and MetS cannot be construed. However, we’ve examined the association of baseline sleep duration with MetS incidence through an incidence analysis among the HEXA-G subjects who have completed the follow-up survey from 2012 to 2015 (54,504 subjects of which 18,522 men and 35,982 women). We found in both men and women who sleep more than 10 h, there was a marginal increased risk of MetS compared to those sleeping 6 to < 8 h (Hazard Ratio (HR): 1.18, 95% CI: 0.88–1.59 in men; HR: 1.19, 95% CI: 0.97–1.46 in women). Although not statistically significant, a prospective cohort study design with the total HEXA-G sample’s sleep duration and risk of MetS are warranted to support these exploratory findings. Second, sleep duration was assessed through self-report questionnaire instead of objective measures via the use of an actigraph or polysomnography. Therefore, it is important to note that ‘sleep duration’ may be reflective of ‘time in bed’, actual time spent asleep, or even how much sleep one believes was attained [42]. Nevertheless, studies have reported that self-report sleep has a moderate correlation (Pearson’s p = 0.31–0.47) to objectively assessed time spent asleep [43, 44] and hence, remains as a useful tool in large epidemiological studies. Third, total sleep time measured may include both nighttime sleep as well as naptime. Daytime napping behavior has been associated with lower sleep efficiency, shorter sleep duration, and consequently cardiovascular risk factors [45]. Hence, it would be informative to make the distinction between naptime and nighttime to separately assess their impact on health. Fourth, no comprehensive data on sleep quality/disturbances was available for analysis. Studies have reported associations between sleep disturbances and cardiovascular and metabolic disorders [38], which point to the importance of including sleep quality/disturbance to assess the effect of sleep on overall health. Fifth, the covariates such as smoking, alcohol drinking, and physical activity were included in the final model as categorical variables. Given that smoking, alcohol drinking, and physical activity are studied to be dose-dependent to health outcomes, there may be residual confounding effect that is not accounted for. Additionally, our study included menopausal status as a binary variable and does not include information on women experiencing menopausal transition, which has been studied to be a contributing factor to sleep patterns in women [22].

Despite these limitations, the current study is the largest study providing dose-response association between sleep duration and metabolic syndrome and its components. Using the HEXA-G database allowing for greater internal validity as well as additional robust subgroup analyses: the sample became more homogenous and the number of women and men have almost doubled from the previous study which gave more power to detect the associations between sleep and MetS that were unnoticed before. Furthermore, with the addition of extended HEXA study years from 2009 to 2013, hour-specific dose-response association was analyzed which highlighted the gender differences in association between sleep and MetS.