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Although commonly used, it is unclear whether TV-viewing is an adequate indicator of sedentary lifestyle. It omits other leisure-time and occupational sedentary behaviours, although >75% of our adults used computers in leisure Mdm2 work shows few weak associations with CVD biomarkers in this population [31]. The socio-demographic and lifestyle characteristics of individuals with greater TV-viewing represent a more adverse diabetes and CVD risk profile [31], raising the possibility of residual confounding. For example, our study does not take account of familial history of cardiovascular risk. Glucose metabolism was indicated by HbA1c because it was impractical to obtain fasting samples in this nationwide, working-age population. While total- and HDL-cholesterol are little affected, Cyclopamine mw triglycerides are lower after fasting and vary by duration of fasting and time of day. Fasting and non-fasting triglycerides are positively correlated [32], and a meta-analysis found no variation in results for triglycerides by fasting status [33], suggesting that such measures are useful in large epidemiological studies. Finally, there has been sample attrition over the years of follow-up in our study. To avoid further loss of data, we used imputation for missing information on covariates. Our finding that 33?y obesity was associated with several diabetes and CVD biomarkers at 45?y, adds to an extensive literature on obesity-related health hazards [1]. Similarly, the observation that associations were largely independent of PA and sedentary behaviour agrees with previous studies [5]. Associations for 33?y obesity may not be as strong as for concurrent obesity: e.g., mean SBP was raised by 5.2 (4.5, 5.9)?mmHg for 33?y obesity compared to 6.9 (6.2, 7.5)?mmHg for 45?y obesity [34]. Hence, our estimates of obesity-related disease risk will be conservative. In considering whether PA or reduced sedentary behaviour could ameliorate the adverse biomarker profile related to obesity, our study adds to existing evidence in two important respects. First, the stronger trend of HbA1c with TV-viewing among obese than non-obese groups is a novel finding, Sotrastaurin in vivo as few studies investigate such variations for sedentary behaviour separately from lack of PA. The role of prolonged sedentary behaviour for elevated risk of diabetes was highlighted by a systematic review and meta-analysis [8], whilst, deleterious effects on glucose levels of uninterrupted compared to interrupted sitting were found in an experimental study of overweight middle-aged adults [35]. Our findings suggest that adverse effects of sedentary behaviour, indicated by longer TV-viewing, are particularly pronounced for obese men and women.