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• W4282032081 abstract "I read with great interest the recent study by Chan and colleagues entitled “Obesity is Associated With Increased of Crohn’s disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Studies.”1Chan S.S.M. et al.Clin Gastroenterol Hepatol. 2022; 20: 1048-1058Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The study was a meta-analysis of prospective cohort studies that demonstrated that in adult populations obesity associates with later onset Crohn’s disease (CD), but not ulcerative colitis (UC). As the authors point out it relates mainly to middle-aged and female subjects who are not typical of most patients with CD, although they are a growing proportion. Our own work suggests that the association of high body mass index (BMI) and obesity with risk of CD is only half the story and that low BMI also associates with increased risk in younger men and women. There is a need for a structured review of this area to incorporate the wider universe of patients with inflammatory bowel disease including studies that may not be able to control as rigorously for all known confounders as in the previously mentioned meta-analysis. In our large prospective study of nearly 400,000 Danish male conscripts recruited at age 19 and followed for 13 million person-years, we demonstrated that the association between BMI and future risk of CD (n = 1523) was U-shaped with minimal risk occurring at BMI of around 22, rising with BMIs below and above this.2Mendall M. et al.Sci Rep. 2019; 9: 6360Crossref PubMed Scopus (8) Google Scholar The U-shaped association of BMI at age 19 with CD persisted through more than 40 years of follow-up suggesting that BMI on entering adult-life associates with a long-standing risk for developing CD unlikely to be explained by preclinical disease. This association was not observed with UC. We argued that these associations could not be explained by smoking behavior, because smoking behavior does not influence BMI until people are older and the effect of smoking on BMI would have to be implausibly large to explain the effects observed. A similar U-shaped association was seen in the Danish National Birth Cohort3Mendall M. et al.PLoS One. 2018; 13e0190600Crossref PubMed Scopus (19) Google Scholar where smoking could be controlled for, and in our original case-control series based on BMI at diagnosis. The Danish male conscripts contrast with the population studied in the recent meta-analysis in being solely male, covering a wider range of ages at diagnosis, and being recruited in an earlier period when obesity was less prevalent. Nevertheless there is the suggestion from the NHSII study that a similar U-shaped association with BMI at age 18 may exist.4Khalili H. et al.Inflamm Bowel Dis. 2015; 21: 361-368Crossref PubMed Scopus (0) Google Scholar In NHSII the underweight category was defined as BMI <20 and associated with a nonsignificantly increased risk of CD, which may have been apparent if the conventional definition of underweight, BMI <18.5, had been used. Supporting evidence for the U-shaped association between BMI and disease risk in general comes from the prospective British General Practice Research Database.5Baskaran K. et al.Lancet Diabetes Endocrinol. 2018; 6: 944-953Abstract Full Text Full Text PDF PubMed Scopus (359) Google Scholar In this large study covering a wide age range in which ever smokers were excluded, a U-shaped association was observed between BMI and mortality from most diseases and cancers including non-liver GI-related deaths. Furthermore, extending the window from measurement to start of follow-up did not affect these associations. Low BMI many years before CD onset could have several explanations. It is unlikely to be caused by residual confounding from smoking, nor by preclinical disease for the reasons alluded to previously. Low BMI could associate with differences in physiologic and immune function that promote risk of CD. For example, low BMI associates with low muscle mass low testosterone, which associates with low muscle mass, has been implicated in the pathogenesis of CD.6Khalili H. et al.Inflamm Bowel Dis. 2015; 21: 1378-1385Crossref PubMed Scopus (86) Google Scholar The role of skeletal muscle in modulating immune function is being increasingly appreciated,7Nelke C. et al.EBioMedicine. 2019; 49: 381-388Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar as is the role that sarcopenia may play in modulating disease activity in patients with CD. As well as further exploration of the association of low BMI and high BMI with risk of CD, work on the association of skeletal muscle mass and function on risk of developing inflammatory bowel disease, and its interaction with body fat mass is also warranted. Such information is not widely available in many large cohort studies, but is available in some.8Frots M.E. et al.J Am Med Dir Assoc. 2014; 15: 448PubMed Google Scholar Obesity is Associated With Increased Risk of Crohn’s disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort StudiesClinical Gastroenterology and HepatologyVol. 20Issue 5PreviewIt is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn’s disease (CD) and ulcerative colitis (UC). Full-Text PDF Open AccessReplyClinical Gastroenterology and HepatologyPreviewWe thank Dr Mendall for the interest regarding our study “Obesity is associated with increased risk of Crohn’s disease, but not ulcerative colitis: A pooled analysis of 5 prospective cohort studies,”1 and drawing our attention to studies reporting an association between low body mass index (BMI) and risk of Crohn’s disease (CD). In the work by Mendall and colleagues, men in early adulthood (age 18–21 years) and women (age 27–34 years) with a low baseline BMI (<18.5 kg/m2) were associated with an increased risk of developing CD in later life. Full-Text PDF" @default.
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• W4282032081 title "Obesity and Risk of Crohn’s Disease Half the Story" @default.
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