Adiposity-mortality relationships in type 2 diabetes, coronary heart disease and cancer populations in the UK Biobank, and their modification by smoking

Objective
The obesity paradox, in which overweight/obesity is associated with mortality benefits, is believed to be explained by confounding and reverse causality, rather than a genuine clinical benefit of excess body weight. We aimed to gain deeper insights in the paradox through: analysing mortality relationships with several adiposity measures; assessing subgroups with type 2 diabetes, coronary heart disease (CHD) and smokers and by adjusting for several confounders.

Research design and methods
We studied the general UK Biobank population (n=502,631), along with 3 subgroups: individuals with a) type 2 diabetes (n=23,842); b) CHD (n=24,268) and c) cancer (n=45790) at baseline. A range of adiposity exposures were considered, including BMI (continuous and categorical), waist circumference, body fat percentage and waist-to-hip ratio, and the outcome was risk for all-cause mortality. We used Cox regression models adjusted for age, smoking status, deprivation, education and disease history.

Results
For BMI, the obesity paradox was observed among people with type 2 diabetes (adjusted HR: obese vs. normal BMI: 0.78, 95% CI: 0.65,0.95), but not among those with CHD (HR: 1.00: 0.86,1.17). The obesity paradox was pronounced in current smokers, absent in never smokers, and more pronounced in men than women. For other adiposity measures, there was less evidence for an obesity paradox, yet smoking status consistently modified the adiposity-mortality relationships.

Conclusions
The obesity paradox was observed in people with type 2 diabetes and is heavily modified my smoking status. The results of sub-group analyses and statistical adjustments are consistent with reverse causality and confounding.