Associations of different body fat components with cardiometabolic and cancer risks

Background: Excess total or central adiposity is associated with intermediate disease markers and increased risks of cardiometabolic disease (CMD) and cancer. However, there is limited evidence on the relevance of visceral and ectopic adiposity, which are more metabolically active and potentially oncogenic. Methods: UK Biobank (UKB) recruited 502,359 participants during 2006-10, among whom 64,025 attended the imaging sub-study subsequently. The correlations between anthropometric and imaging (magnetic resonance imaging [MRI], dual x-ray absorptiometry [DXA]) derived adiposity traits were examined in published studies and UKB. The analyses then examined the associations in UKB of total, central, visceral and ectopic adiposity with levels of 14 disease markers, using linear regression, and with risks of CMD and cancer, using Cox regression. For the entire UKB, adiposity traits were estimated using “imputed category medians” (within BMI deciles at baseline) and analysed continuously to assess risks. Results: Anthropometric measures correlated strongly with imaging-derived total, central and visceral adiposity, but weakly with ectopic adiposity. All adiposity traits per SD increase were associated with disease markers, except oestradiol, with MRI-derived visceral adiposity (i.e. VAT-MRI) exhibiting the greatest associations with most markers and with T2D risk (adjusted HR=2.50 [95% confidence intervals: 2.07-3.00]) compared with BMI (1.79 [1.57-2.04]), waist circumference (WC) (2.11 [1.80-2.48]) and liver adiposity (1.83 [1.58-2.12]). For ischemic heart disease, colorectal, and breast cancer in postmenopausal women, the HRs were modest but differed little across adiposity traits. In analyses of the entire UKB, liver adiposity showed a greater association with endometrial cancer risk (12.88 [10.05-16.51]) than BMI (1.90 [1.78-2.02]), WC (1.99 [1.85-2.14]) and VAT-MRI (2.32 [2.13-2.53]), with similar, albeit less extreme, patterns of associations with risks of colorectal, oesophageal adenocarcinoma, liver, breast, and all cancers combined. Adiposity showed inverse associations with prostate cancer and oesophageal squamous cell carcinoma risks, with no differences between adiposity traits. Conclusions: All body fat components were associated with risks of CMD and cancer and their associated markers, with visceral adiposity having greater associations with certain markers and T2D risk than other adiposity traits, and liver adiposity having the greatest association with most cancers.