Abstract
BACKGROUND: To examine whether general and abdominal adiposity was a risk factor for the new-onset of inflammatory bowel disease (IBD) and the potential mediating effect of metabolic and inflammation status. METHODS: A total of 492,998 individuals free of IBD recruited from 2006 to 2010 in the UK Biobank were included in our study, with ongoing follow-up linking to the health-related outcome. Multivariable Cox regression models were used to evaluate the associations between general adiposity (body mass index) and abdominal adiposity (waist circumference) and the subsequent risk of IBD and its subtype. We also investigated the potential mediating effects of metabolic and inflammation status by carrying out exploratory mediation analyses. RESULTS: During a median follow-up of 12.5 years, we documented 2954 incident IBD cases (915 Crohn's disease [CD] and 2039 ulcerative colitis). After adjustment for important confounders, body mass index (hazard ratio [HR] highest quintile [Q5] vs. lowest quintile [Q1] = 1.18, 95% confidence interval [CI] 1.04-1.32; P-trend = 0.006) and waist circumference (HR (Q5 vs. Q1) = 1.30, 95% CI 1.14-1.49; P-trend <0.001) showed a positive association with the risk of IBD. The associations were partially mediated by metabolic status (24%; 15%), C-reactive protein (36%; 19%) and inflammation score (82%; 46%). CONCLUSIONS: Adiposity bore a risk factor for incident IBD, whereas unhealthy metabolism, especially inflammation, seemed to be an important intermediate condition between the association. Our findings provide evidence for possible mechanisms relating adiposity to IBD from an epidemiological perspective, and experimental studies are needed for further demonstration.