Results suggest sex-specific patterns, since obesity, hypertension and high glycated hemoglobin were associated with self-reported sleep duration and insomnia symptoms (either separately or linked to short sleep duration) in women, but not in men. In addition, cardiometabolic risk factors were associated with insomnia symptoms plus short sleep duration only in women. In relation to hypertriglyceridemia, statistically significant associations with insomnia symptoms were observed among both women and men.
Observational studies have shown that the prevalence of insomnia symptoms varies from 10% to 30%,3,21,25 and similar to our findings, insomnia symptoms are more frequent among women than men.17,25,30 This difference is more evident in self-reported data than objective measures.26 Regarding sleep duration, our findings indicated that almost half of the sample reported short sleep duration. This prevalence was higher than those observed in other countries.11,21,31 However, for long sleep duration, our findings are in agreement with previous studies.22,31
- Sex-specific patterns considering short sleep duration
Some studies reported significant associations between sleep problems and cardiometabolic outcomes for women but not men. Similar to our findings, in the Whitehall cohort, short sleep duration was associated with a higher risk of hypertension only in women.28 Also, Grandner et al.40 evaluated the association between hypertension and sleep duration in a large survey population and observed that short sleep was more closely related to hypertension in women than men. A meta-analysis of the association between sleep duration and hypertension revealed that the results from cross-sectional studies suggested statistically significant associations between short sleep duration and hypertension in women but not in men.8
In relation to body weight, Westerlund et al.30 observed higher BMI values in women and men with short sleep duration compared with adequate sleep duration (6–8 hours). On the other hand, similar to our findings, short sleep duration was associated with a greater BMI among women but not among men.31 A recent meta-analysis6 showed an association between short sleep duration and the risk for obesity (lowest risk at 7-8 hours sleep/day), stressing that the associations seem to be more evident in women than men. However, conclusions were not yet possible given the few studies addressing possible gender differences.6 The same limitation was pointed out by Shan et al.,5 who found an association between short sleep duration and an increased risk for type 2 diabetes in a meta-analysis of prospective studies with adult populations. In contrast, our findings on the association between short sleep duration and high glycated hemoglobin were not statistically significant in women or men, although a greater tendency for a positive association was observed among women. Regarding plasma lipids, similar to our results, Kim et al.41 did not identify associations between short sleep duration and dyslipidemia in women or men. However, meta-analyses highlight the lack of sufficient evidence to support any conclusion on this issue.10,29
- Sex-specific patterns considering long sleep duration
Westerlund et al.30 also observed higher BMI values in women with long sleep duration. In contrast, long sleep duration was associated with lower BMI values in men. Kim et al.41 observed significant associations of long sleep duration with central obesity, low HDL, and high fasting glucose levels among women but not among men. According to our data, long sleep duration was associated with elevated triglyceride levels only among men,41 which deserves further investigations. As mentioned above, recent meta-analyses have addressed the association between sleep duration and cardiometabolic risk factors, but sex-differences approaches are scarce. A reverse J-shaped relationship was described in a recent meta-analysis, with a borderline association between long sleep duration and the risk of obesity.6 A meta-analysis of longitudinal studies that examined the association between sleep duration and diabetes showed that long sleep duration were associated with a significantly increased risk of diabetes compared with 7-8 hours of sleep/day.5
Concerning the U-shaped relationship between sleep duration and hypertension, a meta-analysis found that the results from prospective studies showed that neither short nor long sleep duration was statistically associated with the risk of incident hypertension.8 However, similar to our findings for women, analyses from cross-sectional studies showed that both short and long sleep durations were associated with prevalent hypertension in adults.8 Another meta-analysis of cohort studies showed significant associations between short sleep duration and higher risk of hypertension.3 However, the authors found no statistical evidence of any effect of long sleep duration on the risk of hypertension.3 A meta-analysis of prospective studies identified that short sleep duration was significantly associated with increased risk of obesity, whereas long sleep duration had no effects on obesity.16 A systematic review with meta-analyses examining the relationship between short sleep duration and several health outcomes identified significant results for diabetes, hypertension, cardiovascular disease and obesity.11 The results from this same research group showed that long sleep duration was significantly associated with diabetes and obesity, but not with increased risk of hypertension.12 In summary, the literature is not entirely consistent with respect to the U-shaped associations between sleep duration and metabolic outcomes. Some results from meta-analyses including longitudinal studies have showed statistically significant associations of both short and long sleep duration with diabetes and obesity,5,12 while other studies that evaluated hypertension and obesity did not identify any associations.3,16 Part of these disagreements could be attributed to methodological issues, such as the instrument used to assess sleep duration and the outcomes (subjective or objective measure), the cut-offs for sleep duration, and the duration of follow-up.3
- Sex-specific patterns considering insomnia symptoms
Sex-specific patterns concerning the association between insomnia symptoms and cardiometabolic factors are scarce. Cross-sectional analyses30 showed higher BMI values in women with insomnia symptoms, and a similar pattern but less marked among men. In contrast to our findings, insomnia was associated with a hypertriglyceridemia in women, but significant results were not found in men.29 Also, difficulty maintaining sleep was associated with an increased overall risk for cardiovascular events in women, but not men42.
Regarding data from the general population without discussion of sex-specificities, insomnia symptoms were associated with hypertension medication,44 dyslipidemia medication,44 and type 2 diabetes.7 A meta-analysis of cohort studies showed that insomnia symptoms were significantly associated with a higher risk of hypertension.3 However, among individuals with adequate sleep duration, insomnia symptoms were not associated with obesity.22
- Joint associations of insomnia and short sleep duration
A recent study found a significant association between insomnia symptoms and obesity among participants with short sleep duration, but not among those who reported adequate sleep duration.22 In the same way, short sleep duration with insomnia symptoms was associated with hypertension23 and diabetes.24 In a cross-sectional study, associations between sleep duration and BMI were not modified by insomnia symptoms.30
Our findings on the associations between self-reported sleep duration and each outcome independent of insomnia symptoms (and vice versa) also deserve attention. It has been discussed that insomnia and short sleep duration are distinct aspects of sleep that exhibit intersections. We did not find distinct results after adjusting for insomnia or sleep duration, i.e., the magnitude of the association was similar regardless of the adjustment for the other sleep variable. However, the combination of insomnia symptoms and self-reported short sleep duration appears to intensify the adverse effects of sleep problems separately from the independent associations.20-21 Therefore, in line with previous studies,23-24 we found that the magnitudes of the associations between self-reported short sleep duration plus insomnia symptoms and the outcomes were slightly increased. These findings stress the relevance of considering sleep problems as an additional risk of disease.
- Possible explanations and mechanisms
In line with our findings, Prather et al.27 showed that associations between sleep quality and biomarkers were stronger in women than in men. Poorer sleep quality was associated with 5-years increases in Interleukin 6, C-reactive protein, and fibrinogen in women but not in men. Therefore, causal pathways may be different for men and women. Therefore, causal pathways may be different for men and women. A laboratory study examining the effects of sleep deprivation on neural cardiovascular control in men and women found that sleep deprivation decreased muscle sympathetic nerve activity only in men, which in turn exerted a protective function on blood pressure.43 Concerning differences in levels of reproductive hormones, it is possible that testosterone, which is higher in men, may attenuate the effects of poor sleep on inflammation. Supporting this hypothesis, lower circulating levels of estradiol contribute to the increased levels of inflammatory activity associated with poor sleep in women around the menopausal period (~55 years).27 The association between sleep problems and greater psychological distress in women but not in men26 could also explain these differences. Greater psychological distress in women is generally attributed to a more stressful role for women in Western societies.
Although sex-specific association between sleep and cardiometabolic problems represents an important research area,5-6,32 the mechanisms underlying the different patterns are not completely elucidated because few studies have investigated sex differences related to this issue.41 Therefore, further studies on sex differences and more mechanism studies are needed to clarify this issue.
In a general way, the biological evidence supporting a putative mechanism between sleep deprivation and cardiometabolic outcomes is derived from disturbances in autonomic function, and inflammatory and hormonal profiles.33 For instance, sleep reduction affects energy balance, increases energy intake and reduces energy expenditure. Nocturnal awakening is also associated with altered leptin levels that lead to leptin resistance and result in glucose impairment. Elevated appetite could lead to weight gain and in turn, increases insulin resistance.5,32 Possible pathways for the association between long sleep duration and cardiometabolic disease are not clear. Some authors discuss the possibility that long sleepers are previously sick individuals, and for that reason, these associations should be observed in this group. Long sleep is also associated with others sleep disorders, such as obstructive sleep apnea, and poor-quality sleep (increased sleep fragmentation and more frequent awakenings), which lead to changes in inflammatory markers that have been shown to be associated with metabolic dysregulation.17,33,45 Disagreeing with the hypothesis that morbidity leads to long sleep duration, some studies stress the significant associations of long sleep duration with mortality, diabetes and other diseases, after controlling for other comorbidities.17,45-46 It should be noted that in the study of the joint associations of insomnia and sleep duration with diabetes, the adjustment for body mass index did not attenuate associations of long sleep duration without insomnia and diabetes.17 In this way, a sensitivity analysis by exclusion of the participants diagnosed with myocardial infarction, stroke, and cancer during the first 2 years of follow-up did not change the association between long sleep duration and diabetes.45 Clearly, there is a demand for further studies on long sleepers.
-- Strengths and weakness
The strengths of this study are the large multicenter sample of middle-aged Brazilians, the use of standard equipment and techniques and the rigorous quality control of interviews and all measurements. All outcomes included were evaluated by objective measures. Also, we investigated the relationship between sleep duration and the cardiometabolic risk factors, examining firstly if the shape of these possible associations was linear or nonlinear in order to determine the cut off points for sleep duration based on the patterns of our sample.
The limitations of this study include the fact that all sleep variables were self-reported. Also, the insomnia symptoms did not include information related to daytime dysfunction. Although measuring objective sleep duration is more accurate, this procedure is generally not feasible in large epidemiological samples.5,10 The current study demonstrated substantial reliability for insomnia symptoms and self-reported sleep duration questions. Also, objective sleep-duration measures seemed to be more strongly associated with hypertension than self-reported sleep duration, with no statistically significant differences.3 Second, we did not have enough information to distinguish participants who were naturally short sleepers (short sleep duration but feel rested) from the others, and there may be differences between those groups. However, the investigation of individuals who reported short sleep duration plus insomnia symptoms showed results in the same direction of those observed for short sleepers. Therefore, we supposed that most individuals who reported short sleep duration do not have high sleep quality. Third, although the cross-sectional study design did not allow us to infer causality, the literature on sleep and metabolic disorders suggests that sleep problems most likely enhance the probability of developing cardiometabolic outcomes.24 Fourth, our plasma measures were obtained based on standard procedures between 7:00 a.m. and 10:00 a.m., but the exact moment of assessment was not recorded. As we expect a diurnal variation for some biological markers, the timing of the blood test could be a potential confounder that was not considered. Fifth, we recognize the relevance of age in analysis of cardiometabolic factors. Nevertheless, our sample size (only ~4% reported long sleep duration) did not allow us to deeply study age effects – for instances, only 41 individuals with high glycated hemoglobin levels reported long sleep duration). Finally, our study sample comprises a particular population (Brazilian civil servants) and the generalization of our findings should be done with caution.