Abstract
OBJECTIVE: This study evaluated associations between several obesity indicators and the risks of Crohn's disease (CD) and ulcerative colitis (UC), the two principal clinical phenotypes of inflammatory bowel disease (IBD). METHODS: Data from 479,590 UK Biobank participants (mean age ± standard deviation: 56.5 ± 8.09 years; 54.5% female) were analyzed. Participants were classified based on waist circumference (WC). Cox proportional hazards models were used to quantify associations between multiple adiposity measures and incident CD and UC, adjusting for demographic, behavioral, and clinical covariates. RESULTS: During a median observation period of 12.5 years (maximum 15.6 years), 1,518 incident CD cases and 2,957 incident UC cases were identified. Taking into account demographic variables (age, sex, and ethnic background), lifestyle indicators (including smoking, alcohol intake, sleep, diet, physical exercise, and employment), socioeconomic status measured by the Townsend Deprivation Index(TDI), coexisting conditions (hypertension and diabetes), inflammatory status (C-reactive protein), and nonsteroidal anti-inflammatory drug consumption, waist-to-hip ratio (WHR)-defined central adiposity was found to elevate the risk of CD (hazard ratio [HR] 1.18; 95% confidence interval [CI] 1.05-1.34). However, WC-defined central obesity did not demonstrate a statistically significant link to CD risk (HR 1.11, 95% CI 0.97-1.27). In minimally adjusted models, WHR-defined central obesity was associated with an increased hazard of UC (HR 1.13; 95% CI 1.05-1.23); this association attenuated to non-significance after full covariate adjustment (HR 1.03; 95% CI 0.95-1.13). Obesity defined by BMI ≥ 30 showed no relation to CD, whereas it was associated with a lower hazard of UC (HR 0.86; 95% CI 0.78-0.95). Similarly, higher body-fat percentage (BFP: male > 25%, female > 35%) was associated with a modestly lower hazard of CD (HR 0.92; 95% CI 0.85-0.99). Excluding incident IBD events that occurred during the first 24 months of follow-up, the WHR-CD association persisted (HR 1.19; 95% CI 1.04-1.36). Additionally, individuals in the highest third of WHR-for-BMI residuals (> 66th percentile) exhibited a markedly elevated risk of CD (HR 1.26; 95% CI 1.10-1.44). CONCLUSIONS: Central obesity, assessed by WHR, independently predicts the risk of CD, with a particularly pronounced effect in females, irrespective of BMI or other metabolic confounders. Conversely, higher BMI and BFP were inversely associated with UC risk.