Associations of body fat and inflammation with non-communicable chronic diseases and mortality: a prospective cohort study of the UK Biobank

Objective Certain leading medical organisations are considering alternatives to the Body Mass Index (BMI) as a predictor of the risk for non-communicable chronic disease (NCD) or death. Our objective was to evaluate the associations between various measures of body fat and the risk of incident NCDs or mortality, independent of inflammation. Design Population-based prospective cohort study (the UK Biobank cohort). Setting The UK. Participants Adults (aged between 40 and 69 years) were accrued between March 2006 and October 2010 and followed until December 2022. There were 500 107 participants: the median age was 58 years (IQR 50–63) at baseline, 45.6% were male and 94.7% were white. Exposures BMI, waist-to-hip ratio (WHR), body fat percentage measured by bioimpedance analysis (BIA; fat BIA ), C-reactive protein (CRP) and various other measures of body fat obtained by dual-energy X-ray absorptiometry (DXA; including visceral adipose tissue (VAT)) and magnetic resonance imaging (MRI). Outcomes All-cause death, cardiovascular disease (heart failure, hypertension, myocardial infarction, pulmonary embolism and stroke), cancers (breast, colorectal, endometrial, oesophageal, kidney, ovarian, pancreatic and prostate), diabetes, asthma, gallbladder disease, chronic back pain and osteoarthritis. Results The 5th and 95th percentiles for measures of body fat were BMI 20.5 (considered ‘healthy’) and 37.0 kg/m 2 (considered ‘unhealthy’), WHR 0.71 and 0.94 and BIA 24.8% and 47.6% in females, and BMI 22.0 (considered ‘healthy’) and 35.4 kg/m 2 (considered ‘unhealthy’), WHR 0.83 and 1.05 and BIA 15.5% and 34.7% in males. BMI was strongly correlated to fat BIA (0.85 in females and 0.80 in males) but less so with WHR (0.46 in females and 0.59 in males). All measures of body fat were positively associated with the incidence of NCDs, but only WHR remained positively associated with death after full adjustment (HR 95th percentile vs 5th percentile (95% CI): BMI 0.80 (0.76 to 0.84), WHR 1.21 (1.16 to 1.28) and BIA 0.80 (0.76 to 0.84) in females; BMI 0.89 (0.85 to 0.93), WHR 1.19 (1.14 to 1.24) and BIA 0.89 (0.85 to 0.92) in males). Simpler models that adjusted for age, sex, CRP, WHR and either BMI or fat BIA gave similar results. Associations between body fat and the incidence of NCDs after accounting for the competing risk of death were also similar. Conclusions BMI was strongly correlated with fat BIA , but WHR and visceral adipose tissue percentage were less so. All measures of body fat were associated with the incidence of NCDs, but only WHR was independently associated with mortality. These findings support the hypothesis that body fat may be protective against death and that the excess risk associated with higher WHR may be mediated by something other than body fat.

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