Purpose: To estimate the strength and shape of the dose–response relationship between sedentary behaviour and all-cause, cardiovascular disease (CVD) and cancer mortality, and incident type 2 diabetes (T2D), adjusted for physical activity (PA). Data Sources: Pubmed, Web of Knowledge, Medline, Embase, Cochrane Library and Google Scholar (through September-2016); reference lists. Study Selection: Prospective studies reporting associations between total daily sedentary time or TV viewing time, and ≥ one outcome of interest. Data Extraction: Two independent reviewers extracted data, study quality was assessed; corresponding authors were approached where needed. Data Synthesis: Thirty-four studies (1,331,468 unique participants; good study quality) covering 8 exposure-outcome combinations were included. For total sedentary behaviour, the PA-adjusted relationship was non-linear for all-cause mortality (RR per 1 h/day: were 1.01 (1.00–1.01) ≤ 8 h/day; 1.04 (1.03–1.05) > 8 h/day of exposure), and for CVD mortality (1.01 (0.99–1.02) ≤ 6 h/day; 1.04 (1.03–1.04) > 6 h/day). The association was linear (1.01 (1.00–1.01)) with T2D and non-significant with cancer mortality. Stronger PA-adjusted associations were found for TV viewing (h/day); non-linear for all-cause mortality (1.03 (1.01–1.04) ≤ 3.5 h/day; 1.06 (1.05–1.08) > 3.5 h/day) and for CVD mortality (1.02 (0.99–1.04) ≤ 4 h/day; 1.08 (1.05–1.12) > 4 h/day). Associations with cancer mortality (1.03 (1.02–1.04)) and T2D were linear (1.09 (1.07–1.12)). Conclusions: Independent of PA, total sitting and TV viewing time are associated with greater risk for several major chronic disease outcomes. For all-cause and CVD mortality, a threshold of 6–8 h/day of total sitting and 3–4 h/day of TV viewing was identified, above which the risk is increased.Electronic supplementary materialThe online version of this article (10.1007/s10654-018-0380-1) contains supplementary material, which is available to authorized users.

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Aims/hypothesis Inverse associations between physical activity (PA) and type 2 diabetes mellitus are well known. However, the shape of the dose-response relationship is still uncertain. This review synthesises results from longitudinal studies in general populations and uses non-linear models of the association between PA and incident type 2 diabetes. Methods A systematic literature search identified 28 prospective studies on leisure-time PA (LTPA) or total PA and risk of type 2 diabetes. PA exposures were converted into metabolic equivalent of task (MET) h/week and marginal MET (MMET) h/week, a measure only considering energy expended above resting metabolic rate. Restricted cubic splines were used to model the exposure-disease relationship.Results Our results suggest an overall non-linear relationship; using the cubic spline model we found a risk reduction of 26% (95% CI 20%, 31%) for type 2 diabetes among those who achieved 11.25 MET h/week (equivalent to 150 min/week of moderate activity) relative to inactive individuals. Achieving twice this amount of PA was associated with a risk reduction of 36% (95% CI 27%, 46%), with further reductions at higher doses (60 MET h/week, risk reduction of 53%). Results for the MMET h/week dose-response curve were similar for moderate intensity PA, but benefits were greater for higher intensity PA and smaller for lower intensity activity. Conclusions/interpretation Higher levels of LTPA were associated with substantially lower incidence of type 2 diabetes in the general population. The relationship between LTPA and type 2 diabetes was curvilinear; the greatest relative benefits are achieved at low levels of activity, but additional benefits can be realised at exposures considerably higher than those prescribed by public health recommendations.

This systematic review and meta-analysis examines data from published prospective studies of adults to gauge the dose-response association between physical activity and incident depression.