Risk of De-novo Inflammatory Bowel Disease Among Obese Patients Treated With Bariatric Surgery or Weight Loss Medications

Gursimran S. Kochhar; Aakash Desai; Aslam Syed; Abhinav Grover; Sandra El Hachem; Heitham Abdul-Baki; Preethi Chintamaneni; Elie Aoun; Sowjanya Kanna; Dalbir S. Sandhu; Siddharth Singh; Bo Shen; Edward V. Loftus Jr; Parambir S. Dulai

Disclosures

Aliment Pharmacol Ther. 2020;51(11):1067-1075. 

In This Article

Discussion

Using a large EMR-based cohort of over 60 million lives we made several key observations which help to better inform our understanding of the risk of de-novo IBD after surgical or medical treatment for obesity.[21] First, the risk of de-novo IBD after exposure to bariatric surgery or weight loss medications is significantly lower than among patients with persistent obesity for at least 2 years who were not exposed to these interventions. Second, this reduction in risk for de-novo IBD after exposure to bariatric surgery was consistent across all surgical interventions for both de-novo UC and CD. Third, the reduction in risk for de-novo IBD after exposure to weight loss medications was predominantly seen among medications known to be more efficacious in helping to achieve weight loss, with no significant association being observed between exposure to orlistat and risk of de-novo UC or CD.[22] Finally, among the patients exposed to bariatric surgery, we observed that the risk reduction for the development of de-novo IBD was predominantly seen in individuals who were able to achieve normalisation of BMI within 1 year of the surgery. Taken together, these data might suggest that persistence of obesity and ineffective management of obesity are key determinants of developing IBD.

Our work helps to expand on prior work by better clarifying the associations between weight loss interventions and risk of de-novo IBD. The two prior studies which suggested an increased risk for de-novo IBD after bariatric surgery were notable for the fact that the patients who developed de-novo IBD after bariatric surgery were obese at the time of diagnosis. Furthermore, the study by Ungaro et al specifically noted that a remote exposure to bariatric surgery, but not a recent exposure, was associated with an increased risk for de-novo IBD.[12] These indirect observations, alongside a growing body of evidence that obesity may be linked to IBD-specific immune mechanisms and pathology, suggest instead that the obesity, lack of adequate weight loss or weight regain after bariatric surgery might have been a risk factor for de-novo IBD as opposed to the intervention itself. We confirmed this hypothesis in this study and further strengthened this through the observed reduction in risk for de-novo IBD with exposure to weight loss medications which do not alter the anatomy of an individual. The role of obesity in causing IBD has been of interest of the medical community for some time. There have been few studies and a recent meta-analysis that have revealed positive associations between obesity and risk of de-novo IBD.[23] However, only few possible mechanisms that explain these and our findings have been hypothesised. An avenue through which colonic inflammation can become dysregulated is through altered adipokine levels in obesity. Additionally, study of certain genetic mutations found in human IBD patients, and the digestion of a high fat diet has been found to potentiate colonic inflammation and cause changes in the microbiome.[24] However, this hypothesis needs to be explored further. Some authors have suggested and also explored the role of visceral adiposity as a risk factor for CD. In one such study, authors looked at the patients from POCER study and concluded that visceral adiposity was an independent risk factor for recurrence of CD after a surgery. Patients with visceral adiposity had RR of 2.1% (95% CI 1.5–3.0, P = 0.012) for endoscopic recurrence at 18 months compared with control population.[25] Authors concluded increased visceral adipose tissue was associated with alterations in gut biome which was similar to the ones seen in patients with IBD.[25] In another study, visceral adiposity independently posed a significant risk of developing penetrating disease and risk of surgery related to CD.[26] Further research is needed to understand how visceral adiposity changes with overall weight and BMI, and how different weight loss interventions influence visceral adiposity.

To the best of our knowledge, this is the single largest study reporting occurrence of de-novo IBD after exposure to bariatric surgery, and the only study evaluating the risk of de-novo IBD after exposure to weight loss medications. The strengths of the study include the large population of patients examined, the ability of Explorys to track patients as they transition between healthcare institutions, large event rate, the ability to assign temporal associations between exposures, availability of BMI and the ability to compare risk across different types of bariatric surgery and weight loss medication exposures.

Limitations of this study do exist which warrant consideration when interpreting findings. We excluded patients on 5-ASA which could resulted in exclusion of milder cases of ulcerative colitis. However, we hope that it would not have impacted our results significantly due to the relatively small number of such patients expected in the database. We could not ascertain duration of follow-up for individual patients, and therefore incidence rates and standardised incidence rates could not be calculated. A risk therefore exists that differential attrition between cohorts may influence our observations; however, confidence is taken in the consistency of observations across various subgroup analyses. The indication of exposure to weight loss medications could not be reliably confirmed to be for the purposes of weight loss, and some overlap likely exists when using medications for the management of diabetes. Another limitation of the study is that BMI is not an accurate measure of visceral obesity, however, BMI has been associated with relevant clinical outcomes such as metabolic syndrome and related morbidity.[27] Finally, as with all claims or coding-based studies, results are susceptible to errors in coding or documentation. The de-identified nature of the data also prevents us from exploring alternative predictors of de-novo IBD or adjusting for potential confounders beyond those easily ascertained with pre-specified codes.

In summary, we observed that exposure to bariatric surgery is not a risk factor for de-novo IBD. Alternatively, effective management of obesity through surgical or pharmaceutical interventions appears to be associated with a risk reduction for de-novo IBD compared with persistently obese patients. Future research is needed to understand the mechanism behind persistent or refractory obesity and development of inflammatory bowel disease as this might provide insights into disease pathogenesis and global prevention strategies.

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