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Adults With Obesity See Increased Risk for Crohn's Disease

— Growing obesity burden may contribute to rise in Crohn's incidence, researcher suggests

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A computer rendering of a colonoscopy of a large intestine with Crohn’s disease.

Obesity in adulthood was associated with a 34% increased risk for developing Crohn's disease, while no such link was seen with ulcerative colitis, a pooled analysis of large prospective studies found.

Compared to adults with a normal body mass index (BMI) at baseline, those with a BMI of 30 or above had a higher risk of older-onset Crohn's disease, with a pooled adjusted hazard ratio (aHR) of 1.34 (95% CI 1.05-1.71), reported Simon Chan, MD, of the Norfolk and Norwich University Hospital NHS Trust in England, and colleagues.

Across the entire study population, each 5 BMI increase was associated with a 16% higher risk for developing Crohn's disease (aHR 1.16, 95% CI 1.05-1.22), reaching 22% for every 5 BMI increase among 18- to 20-year-olds (aHR 1.22, 95% CI 1.05-1.40), according to the findings in .

Meanwhile, the researchers found no relationship between the risk of ulcerative colitis for people with a BMI of 30 or higher (aHR 0.88, 95% CI 0.72-1.08).

"Our data implies that the growing burden of obesity may be contributing to the increasing incidence of Crohn's disease worldwide," Chan told ֱ.

"Previous epidemiology studies had not established a consistent link between obesity and risk of CD [Crohn's disease] and UC [ulcerative colitis]," he continued. "This was likely to be due to significant limitations of past studies, including retrospective design, smaller sample size, and inability to control for confounding from other important life-style exposures and lack of detailed measures of obesity."

In 2005, the prevalence of obesity in Western Europe and the U.S. was 15% to 29%, increasing to 20% to 36% by 2016. Assuming a causal relationship, the authors noted, would yield an attributable risk of Crohn's disease ranging from 5% to 11%.

"Future work will consider examining the precise mechanisms through which obesity may influence the etiopathogenesis of CD," said Chan.

"Our observation that BMI in early adulthood is associated with increased risk of later-onset CD is supported by a that reported obesity in childhood (age 8-13 years) is associated with CD before the age of 30 years," Chan's group noted.

"Obesity, and in particular mesenteric fat, is associated with a proinflammatory state that contributes to the metabolic syndrome and is associated with other 'western diseases' including diabetes and coronary artery diseases," Stephen B. Hanauer, MD, of Northwestern University in Chicago, told ֱ. "Increased intestinal permeability is another potential contributor and may more directly impact on development of CD."

Hanauer, who was not involved with this study, cautioned that the findings "remain associative rather than causative" and will require further scrutiny in other age groups, "including young adults who have the greatest predilection as well as phenotypic attributes of 'obesity-associated' CD."

"Further dietary contributions, impact on microbiome, and other potential confounders require additional investigations to provide clearer insights into potential causation," he said.

examining associations between obesity and inflammatory bowel disease (IBD) have shown inconsistent findings. Therefore, the group aimed to further assess the question in the largest study to date, using a pooled analysis of five prospective cohorts included in Dietary and Environmental Factors IN-IBD (DEFINe-IBD), an international consortium of cohort studies in the U.S. and Europe.

In all, 601,009 participants from nine countries were included, with an average follow-up of 16 years. Participants ranged in age from 18 to 98, though most were in middle-age, and 71% were women. Overall, 1,047 participants had ulcerative colitis and 563 had Crohn's disease.

Measurements were taken for waist-to-hip ratios and BMI at baseline, in addition to lifestyle factors. Individuals with a low BMI (<18.5), incident Crohn's disease, and those diagnosed with IBD within 2 years of follow-up were excluded. People with the highest BMIs were more likely to smoke and exercise less compared to those with normal or average BMIs.

Hazard ratios were adjusted for smoking status, sex, physical activity, dietary fiber (Crohn's) or fat (ulcerative colitis), as well as total fat, fiber, or energy intake. BMI was used as a co-variable to assess secondary exposures.

Limitations of the study included the use of exposure assessment questionnaires that were given to various participants to calculate BMI over multiple durations (spanning 1986 to 1997), which could have changed over time. Also, measurements were only taken at a single timepoint. The researchers further noted the limited number of cases of Crohn's disease in those ages 18 to under 40.

Finally, since participants were mostly middle-age Westerners, Chan and co-authors acknowledged that the findings may not extend to non-Westerners or younger IBD patients. They also noted that life exposures and environmental factors attributing to the findings were also not fixed and remain subjective.

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    Zaina Hamza is a staff writer for ֱ, covering Gastroenterology and Infectious disease. She is based in Chicago.

Disclosures

Research grant funding was provided by the Crohn's and Colitis Foundation, and other funding for the studies came from various government agencies and other organizations in the U.S. and Europe.

Chan disclosed travel grants from Abbvie and Takeda. Co-authors declared relationships with Takeda, AbbVie, Pfizer, Janssen, Ferring, the Swedish Inflammatory Bowel Disease Register, Boehringer Ingelheim, and Bayer Pharma AG.

Primary Source

Clinical Gastroenterology and Hepatology

Chan SSM, et al "Obesity is associated with increased risk of Crohn's disease, but not ulcerative colitis: A pooled analysis of five prospective cohort studies" Clin Gastroenterol Hepatol 2021; DOI: 10.1016/j.cgh.2021.06.049.