Background Obesity is associated with increased mortality, cardiovascular disease (CVD), type 2 diabetes (T2D) and associated biomarkers. A key priority is to minimise such obesity-related consequences for the substantial proportion of adults now at risk. Potential modifiable factors, such as physical activity (PA) and sedentary lifestyles could mediate or moderate the obesity - ill-health association. However, research is scant on whether benefits of activity vary by obesity status across multiple biomarkers and whether there are corresponding patterns for sedentary behaviour. To establish whether the obesity −CVD and T2D risk associations can be lessened by PA or lower sedentary behaviour we aimed to assess whether (i) obesity, PA and sedentary behaviour are independently associated with biomarkers for CVD and T2D, and (ii) PA or sedentary behaviour moderate the obesity-biomarker associations.

Methods In the 1958 British birth cohort (N = 9377) we examined associations between early adulthood obesity (33y) with subsequent biomarkers (45y) together with PA and sedentary behaviour (indicated by TV-viewing) recorded before or at 45y. The temporal sequence follows the ordering of potential interventions to reduce health burdens associated with obesity. Analyses were sex-specific, adjusted for covariates and used multiple imputation to account for missing data.

Results Obesity was associated with lower HDL-cholesterol and higher systolic (SBP), diastolic (DBP) blood pressure, glycosylated haemoglobin (HbA1c) and triglycerides in both sexes (LDL-cholesterol in women only) by 4.30% (95% CI 3.19, 5.41) for SBP to 24.7% (18.8, 30.4) for triglycerides. Men active at least weekly had 1.09% (0.28, 1.90) lower DBP than less active men; triglycerides were 2.08% (0.52, 3.64) lower per unit higher PA (on 4-point scale). TV-viewing was independently associated with several biomarkers, e.g. per unit higher TV-viewing (on 4-point scale) DBP was raised by 0.50% (0.09, 0.90) and triglycerides by 3.61% (1.58, 5.64). For both TV-viewing and PA, associations with HbA1c were greatest for the obese (p-interaction≤0.04): compared to a reference value of 5.20 HbA1c% in non-obese men viewing 0–1h/day, HbA1c% differed little for those viewing >3 h/day; however, among obese men HbA1c% was 5.36 (5.22, 5.51) and 5.65 (5.53, 5.76), for 0–1 and >3 h/day respectively. For PA in non-obese men, the reduction associated with activity at least weekly was negligible compared to a reference value of 5.20 HbA1c% for those less active; but there was a benefit among obese men, HbA1c% was 5.50 (5.40, 5.59) vs 5.66 (5.55, 5.77) respectively.

Conclusion Reduced sedentary behaviour and prevention of infrequent activity has greatest benefit among obese groups, particularly for glucose metabolism.