Introduction
Central obesity, dysglycaemia, dyslipidaemia and hypertension are closely related cardiometabolic abnormalities that cluster in a large proportion of the adult population worldwide. This cluster of factors substantially increases the risk of developing type 2 diabetes, as well as cardiovascular and other chronic diseases [
1,
2]. Insufficient moderate-to-vigorous physical activity (MVPA) is a recognised contributor to elevated cardiometabolic risk levels [
3] and has been targeted by lifestyle interventions in adults at high risk of type 2 diabetes. However, such interventions have had limited success, resulting in relatively modest changes in MVPA [
4].
Excessive time spent sedentary is associated with an increased cardiometabolic risk, independent of time spent in MVPA, and has been suggested as a potential target for lifestyle interventions [
5‐
9]. Sedentary behaviour represents any waking behaviour characterised by an energy expenditure of ≤1.5 metabolic equivalents (METs) while in a sitting or reclining posture [
10]. Adults, on average, spend more than 7 h of the waking day sedentary [
11], an amount that is relatively independent of the time spent in MVPA [
12]. However, there is currently insufficient evidence to establish a longitudinal association between sedentary time and cardiometabolic risk [
13]. The few longitudinal studies examining this hypothesis [
14‐
17] have mainly focused on self-reported television viewing as a marker of leisure-time sedentary behaviour [
15,
16]. Although television viewing is a potentially interesting intervention target, it is only one aspect of sedentary time and its association with cardiometabolic risk may differ from that of overall sedentary time [
7,
18].
Because individuals at high risk of diabetes experience difficulties in increasing their MVPA [
4], identifying additional behavioural targets should inform the development of future preventive interventions in these populations. Longitudinal investigations incorporating objectively quantified time spent sedentary and in MVPA, as well as television viewing time, can provide novel insights into whether, and to what extent, changing these behaviours will independently impact cardiometabolic risk. Furthermore, elucidating whether these associations are predominantly explained by a change in adiposity or by alternative physiological processes will provide insight into the mechanism underlying these associations [
19]. Central obesity is regarded as an important aetiological component in the clustering of elevated cardiovascular risk factors and may therefore act as a mediator [
20].
We aimed to estimate the independent associations between changes in objectively measured time spent sedentary, in MVPA and in self-reported television viewing over 6 years and changes in clustered and individual cardiometabolic risk factors in adults with a parental history of type 2 diabetes. We also examined whether these associations were mediated by a change in central or general adiposity.
Methods
We performed a cohort analysis of the ProActive trial, the design of which is described in detail elsewhere [
21]. In short, ProActive evaluated the efficacy of a theoretical, evidence- and family-based intervention programme that aimed to increase physical activity levels in adults who were at high risk of type 2 diabetes by virtue of having a parent with the disease. Out of 465 eligible individuals aged 30–50 years, 365 were randomly assigned to one of three interventions delivered over 1 year. There was no significant difference in accelerometry-determined physical activity between the three trial arms at 1 year [
22]. Consequently, a cohort analysis was conducted after pooling data from the three trial arms. Participants with valid accelerometry data at 1 and 7 years of follow-up (referred to below as baseline and follow-up, respectively) (
n = 202) constituted the sampling frame for this study, as this provided the optimal combination in terms of follow-up time and number of participants with complete accelerometry data. A final sample of 171 participants was included in analyses, after excluding those with missing cardiometabolic variables (
n = 23), covariates (
n = 6) or unrealistic data (television viewing time > objectively measured sedentary time;
n = 1). We also excluded 1 person who became a wheelchair user during follow-up. All participants provided written informed consent and ethical approval was obtained from the Cambridge Central Research Ethics Committee (reference number: 09/110308/3). All investigations were carried out in accordance with the principles of the Declaration of Helsinki.
Discussion
Increasing sedentary time was independently associated with increasing clustered cardiometabolic risk and triacylglycerol over 6 years in adults with a parental history of type 2 diabetes. Increased MVPA was associated with reduced waist circumference. As one of the first longitudinal studies to examine the associations between sedentary time and cardiometabolic risk in adults at high diabetes risk, we have highlighted the potential benefits of targeting a reduction in sedentary time in future interventions. In context, based on our findings for triacylglycerol levels, decreasing sedentary time by 2 h/day would be associated with an approximately 7% lower risk of cardiovascular events [
33]. This is a feasible reduction in sedentary time, as indicated by a recent lifestyle intervention [
34].
Our findings extend previous cross-sectional findings in other adult populations of the independent associations between sedentary time and clustered cardiometabolic risk [
35] and triacylglycerol levels [
6]. The association with change in HDL-cholesterol did not reach statistical significance in our study, although it was in the hypothesised direction, which is consistent with cross-sectional findings from the Health Survey for England [
7]. It is, however, in disagreement with the National Health and Nutrition Examination Survey, in which a significant cross-sectional association was found with HDL-cholesterol (albeit most strongly in men and non-Hispanic whites) [
6], as well as with the findings from Cooper et al showing a prospective association with HDL-cholesterol in English adults with newly diagnosed type 2 diabetes [
14]. Evidence that sedentary time might influence waist circumference and glucose metabolism is also mixed, in both cross-sectional [
6,
7,
23,
35‐
37] and longitudinal studies [
14,
17,
38‐
40]. Although physiological mechanisms need further clarification [
19], some of the inconsistent findings to date may, in part, be explained by differences in the populations studied (e.g. health risk status, ethnicity [
6] and age) as well as differences in the underlying confounding structures. Our non-significant findings for blood pressure are in agreement with the results from most previous studies [
6,
7,
23,
35].
Few significant independent associations were found for change in MVPA in our study. This may indicate that solely focusing on increasing MVPA, a potentially challenging lifestyle target for high-risk individuals [
4], may not be the most effective strategy for future interventions [
23]. The lack of associations may, however, be explained to some extent by the limited change in MVPA between baseline and follow-up. The relatively small sample size may also partly account for the lack of significant findings, not only for MVPA, but also for the other exposure variables. Nevertheless, even though our findings were not statistically significant, they were generally in the hypothesised directions. In addition, the strengths of the associations are consistent with those from previous studies. Healy et al, for example, showed that sedentary time was more strongly associated with triacylglycerol levels than with HDL-cholesterol levels, and with serum insulin as compared with fasting plasma glucose [
6]. Change in central obesity is a potential mediator [
20], but we found no evidence that these associations were mediated by changes in general and central adiposity. An alternative biologically plausible mechanism underpinning the detrimental effects of prolonged sitting on triacylglycerol involves reduced lipoprotein lipase activity as a result of fewer skeletal muscle contractions [
41].
Individuals at high risk of diabetes enrolled in lifestyle intervention programmes demonstrate limited success in increasing their MVPA levels [
4]. Replacing sedentary time with light-intensity activities that are part of daily living might be an important intervention target. The vast majority of the waking day is spent either sedentary or in light-intensity activity [
35], and changes in time spent sedentary and in light-intensity activity over 6 years were highly correlated (−0.47). This population thus makes most of its transfers in terms of time use between activities of light and sedentary intensity. The importance of total daily physical activity, rather than MVPA alone, on cardiometabolic risk has been shown before, specifically in high-risk adults [
23].
The significant associations between change in television viewing and clustered cardiometabolic risk, waist circumference, fasting plasma glucose and serum insulin were attenuated after adjustment for objectively measured MVPA, indicating they are not independent of MVPA. This may suggest that previous associations between television viewing time and cardiometabolic health, which adjusted for MVPA measured by self-report and were sometimes restricted to leisure-time MVPA only [
5,
8,
15,
16,
18,
42], may have been affected by residual confounding for this key variable. Future investigations of the health implications of sedentary behaviour are therefore encouraged to use objective measures of physical activity.
The differential associations for television viewing and sedentary time with cardiometabolic risk found in the current study indicate that findings for television viewing should not be generalised to overall sedentary time. Television viewing in this population represented less than a third of objectively measured sedentary time and correlations between both indicators were weak. In contrast, two previous investigations showed stronger associations between self-reported television viewing time and cardiometabolic risk compared with objectively measured sedentary time, albeit derived from cross-sectional data [
7,
36]. A study in adults aged ≥60 years [
36], who on average watched more television than younger age groups, showed stronger associations between television viewing and objectively measured sedentary time compared with younger age groups [
43]. Future large longitudinal cohort studies covering a wide age range, and also including a whole set of cardiometabolic risk indicators and appropriately accounting for confounding factors, are needed to further explore the differential role of television viewing and sedentary time in determining cardiometabolic health.
To the best of our knowledge, this is the first longitudinal study simultaneously examining the associations of total sedentary time, television viewing time and MVPA time with clustered cardiometabolic risk and a wide set of individual risk factors. All risk factors were used continuously, which optimised statistical power. It is unclear whether participants changed their sedentary time before any changes in cardiometabolic risk, which hampers inferences on the direction of causality. Change in waist circumference has been shown to predict an increase in sedentary time in a healthy, middle-aged white population [
40]. However, unlike most previous research, our change models examined within-participant effects, which are less prone to unmeasured time-independent confounders (e.g. genetic factors) because each individual acts as his/her own control. Other major strengths of this study include the objective measurement of two of the three exposures, which substantially reduced measurement error. Participants were followed for longer than 6 years. Finally, the mediation effect of general and central adiposity was also explored using the product of coefficient method [
31].
The following limitations should, however, be considered. Participants included in the current study were slightly more educated than those who were excluded, but did not differ in terms of cardiometabolic, sedentary or activity profile, BMI, sex or age. Nevertheless, the relatively small sample of white adults with a high risk for type 2 diabetes included in this study might limit the external validity of the observed associations. Future longitudinal studies in more heterogeneous populations should explore the relative importance of a change in these three behaviours for cardiometabolic health. Television viewing time was self-reported, which confers greater measurement error and is likely to have attenuated any associations, compared with objectively measured exposures. However, assuming participants’ misreporting behaviour would remain constant between baseline and follow-up, a change in television viewing should be captured with lower measurement error compared with television viewing time measured at just one time point.
Participants wore the accelerometer for 4 consecutive days, not necessarily including a weekend day. Sedentary and MVPA time might therefore not be completely reflective of participants’ habitual long-term behaviour. Despite controlling for several potential confounding variables, some findings could still be partially explained by other factors that were not measured, such as alcohol intake, employment status and type of work, or only partially measured (e.g. SES by means of age at finishing full-time education). Given the lack of dietary information, the mediating role of snacking and overall dietary quantity and quality, which are especially relevant for television viewing, could not be explored. Finally, to examine our research question, we conducted a number of significance tests, which might have increased the risk of type 1 errors. Future longitudinal research will help to confirm our findings.
In conclusion, in adults at high risk for type 2 diabetes, increasing sedentary time was independently associated with increasing clustered cardiometabolic risk and triacylglycerol levels. Replacing sedentary time by light-intensity activity, and thus increasing overall daily physical activity levels, could be an important behavioural target in these high-risk individuals. Further longitudinal observational studies are now needed to extend these findings to other populations that are heterogeneous in terms of age, ethnicity and health status, as well as intervention studies, both physiological and free-living, examining acute and longer-term effects to further investigate the direction and mechanism of causality.
Acknowledgements
The ProActive research team includes, besides the authors, K. M. Williams (study coordination, Primary Care Unit, University of Cambridge, UK), J. Grant (study support, Primary Care Unit, Cambridge, UK), A. T. Prevost (study statistician, Primary Care Unit), W. Hollingworth (study economist, University of Bristol, Bristol, UK), N. J. Wareham (principal investigator, MRC Epidemiology Unit, Cambridge, UK), D. Spiegelhalter (principal investigator, MRC Biostatistics Unit, Cambridge, UK), W. Hardeman (principal investigator, Primary Care Unit), S. Sutton (principal investigator, Primary Care Unit), and A. L. Kinmonth (principal investigator, Primary Care Unit). We thank the study participants and practice teams for their collaboration and work in helping with recruitment.