11December2018

Obesity in IBD

Marjo Campmans-Kuijpers, D-ECCO Member

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Marjo Campmans KuijpersMarjo Campmans-Kuijpers
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Although Inflammatory Bowel Disease (IBD) has been historically associated with underweight and malnutrition, rates of obesity have been rising in patients with IBD, as in the general population. Nowadays, 15%–40% of adults with IBD are obese, and an additional 20%–40% are overweight [1]. Obesity is independently associated with higher disease burden and costs of hospitalisation in patients with IBD [2].

IBD may be an independent risk factor for development of obesity driven by dysbiosis and changes in the intestinal microbial metabolism [3,4]. Recent evidence implies that changes in the intestinal immune system contribute to metabolic disease [3]. Furthermore, in patients with IBD, serum levels of adiponectin, resistin, and active ghrelin are increased, whereas serum levels of leptin are decreased [4]. In addition, drug treatment used for IBD, in particular corticosteroids and anti-tumour necrosis factor alpha (TNF) therapies, may also increase obesity [1]. Conversely, obesity is associated with changes to the gut microbiota and intestinal barrier function and predisposes to altered intestinal immunity [2,4], and metabolically active adipose tissue might contribute to a pro-inflammatory susceptibility to IBD [3].

Existing data on the impact of obesity on IBD susceptibility and disease course are, however, inconsistent. One study in IBD patients found obesity not to be significantly associated with the odds of achieving clinical remission, clinical response or mucosal healing during either induction or maintenance therapy [5]. Pharmacokinetic studies of several anti-TNF agents in patients with immune-mediated inflammatory diseases have demonstrated accelerated drug clearance with increasing body weight [6–8], and this is probably also true in IBD [9]. A recent study showed a high body mass index (BMI) to be independently associated with an increased risk of treatment failure and surgery in biologic-treated patients with Ulcerative Colitis (UC) [10]. This inconsistency in data may explained by the fact that most studies use only BMI to measure adiposity.

BMI is unable to distinguish between lean body mass and other tissues. Therefore, sarcopenia (low lean mass) is difficult to detect. Current data on sarcopenia in IBD are scarce due to retrospective study designs and inappropriate functional assessment [11]. Sarcopenia has been associated with an increased need for surgery and poor surgical outcomes in IBD, as well as with osteopenia [12–14], and it has been found to be a significant (p=0.002) predictor of need for surgery in overweight and obese subjects [2].

Furthermore, different adiposity compartments have distinct metabolic profiles [12]. In many patients with Crohn’s Disease (CD), visceral adipose tissue is increased [12] and it has been reported that increased visceral to subcutaneous fat ratio is associated with a higher postoperative inflammatory response (higher procalcitonin levels) in IBD patients undergoing colorectal resection [15]. In addition, patients with CD (but not those with UC) have a unique form of visceral adipose tissue, mesenteric fat hyperplasia (“creeping fat”), that is limited to areas of inflamed bowel [16]. This mesenteric fat increases C-reactive protein and may contribute to systemic obesity.

A recent study found that the increasing rates of obesity in patients with IBD coincide with decreases in lean muscle mass over time, while high rates of osteopenia remain stable [17]. Therefore, better assessment of body composition and studies on fat deposition in IBD patients are urgently needed to guide therapy on both sarcopenia and pro-inflammatory fat depositions.

References

  1. Singh S, Dulai PS, Zarrinpar A, Ramamoorthy S, Sandborn WJ. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017;14:110–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27899815 
  2. Nguyen NH, Ohno-Machado L, Sandborn WJ, Singh S. Obesity is independently associated with higher annual burden and costs of hospitalization in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2018 Sep 27 [Epub ahead of print]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30012429
  3. Winer DA, Luck H, Tsai S, Winer S. The intestinal immune system in obesity and insulin resistance. Cell Metab. 2016;23:413–26. Available from: http://dx.doi.org/10.1016/j.cmet.2016.01.003
  4. Karmiris K, Koutroubakis IE, Xidakis C, Polychronaki M, Voudouri T, Kouroumalis EA. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12:100–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16432373
  5. Singh S, Proudfoot J, Xu R, Sandborn WJ. Impact of obesity on short- and intermediate-term outcomes in inflammatory bowel diseases: Pooled analysis of placebo arms of infliximab clinical trials. Inflamm Bowel Dis. 2018;24:2278–84. Available from: https://academic.oup.com/ibdjournal/advance-article/doi/10.1093/ibd/izy135/4999331
  6. Wade JR, Parker G, Kosutic G, et al. Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn’s disease. J Clin Pharmacol. 2015;55:866–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25735646
  7. Passot C, Mulleman D, Bejan-Angoulvant T, et al. The underlying inflammatory chronic disease influences infliximab pharmacokinetics. MAbs. 2016;8:1407–16. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27589009 
  8. Mostafa NM, Nader AM, Noertersheuser P, Okun M, Awni WM. Impact of immunogenicity on pharmacokinetics, efficacy and safety of adalimumab in adult patients with moderate to severe chronic plaque psoriasis. J Eur Acad Dermatology Venereol. 2017;31:490–7.
  9. Singh S, Facciorusso A, Singh AG, et al. Obesity and response to anti-tumor necrosis factor-α agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis. PLoS One. 2018;13:e0195123. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29771924
  10. Kurnool S, Nguyen NH, Proudfoot J, et al. High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis. Aliment Pharmacol Ther. 2018;47:1472–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29665045
  11. Bryant RV, Trott MJ, Bartholomeusz FD, Andrews JM. Systematic review: body composition in adults with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38:213–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23763279
  12. Adams DW, Gurwara S, Silver HJ, et al. Sarcopenia is common in overweight patients with inflammatory bowel disease and may predict need for surgery. Inflamm Bowel Dis. 2017;23:1182–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28410342
  13. Bamba S, Sasaki M, Takaoka A, et al. Sarcopenia is a predictive factor for intestinal resection in admitted patients with Crohn’s disease. PLoS One. 2017;12:1–12.
  14. Pedersen M, Cromwell J, Nau P. Sarcopenia is a predictor of surgical morbidity in inflammatory bowel disease. Inflamm Bowel Dis. 2017;23:1867–72.
  15. Wei Y, Zhu F, Gong J, et al. High visceral to subcutaneous fat ratio is associated with increased postoperative inflammatory response after colorectal resection in inflammatory bowel disease. Gastroenterol Res Pract. 2018; 6270514. Available from: https://www.hindawi.com/journals/grp/2018/6270514/ 
  16. Peyrin-Biroulet L, Gonzalez F, Dubuquoy L, et al. Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn’s disease. Gut. 2012;61:78–85. 
  17. Bryant R, Schultz C, Ooi S, et al. Obesity in inflammatory bowel disease: Gains in adiposity despite high prevalence of myopenia and osteopenia. Nutrients. 2018;10:1192. Available from: http://www.mdpi.com/2072-6643/10/9/1192

Posted in Committee News, D-ECCO, Volume 13, Issue 4