How obesity affects IBD management and patient outcomes: Q&A with Amanda M. Johnson, M.D.

Feb. 05, 2021

In this Q and A, Amanda M. Johnson, M.D., discusses the prevalence of obesity in patients with inflammatory bowel disease (IBD), obesity's potential role in the pathogenesis of IBD and current thinking about management of patients with IBD who are obese. Dr. Johnson is a gastroenterologist specializing in IBD at Mayo Clinic's campus in Rochester, Minnesota, who co-authored a review article on this topic in Gastroenterology and Hepatology in 2020.

What is the prevalence of obesity in patients diagnosed with IBD, and why is this an important topic to explore?

I think it is important to recognize that obesity is very prevalent within the IBD population. When we think about patients with IBD, there is a tendency to envision a population of patients who are underweight and malnourished. However, this is simply not the case.

We performed a study of all patients who received a diagnosis of IBD within Olmsted County from 1970 through 2010. Within that population, we found that the prevalence of obesity increased twofold to threefold when we compare those diagnosed from 1970 to 1980 with those diagnosed from 2000 to 2010. The reality is that the current prevalence of obesity among patients with IBD now parallels that of the general population. An estimated 15% to 40% of patients diagnosed with IBD are obese, with a body mass index (BMI) of 30 or higher. And when we add individuals who are overweight, those with a BMI of 25 to 30, that category includes nearly 60% of patients with IBD.

What is known about the impact of obesity on the natural history and outcomes of IBD?

While the ever-increasing prevalence of obesity within the IBD population is well documented in several studies, what remains unclear is the impact this may have on the clinical course of the IBD itself. Data pertaining to the impact of obesity on future IBD-specific outcomes is not only sparse, but conflicting. Some suggest that obesity may increase the risk of complications such as hospitalization, intestinal resections or corticosteroid use; however, there are also studies documenting that the risk of such complications is lower or even the same in patients who are obese when compared with individuals who are normal weight. With these mixed findings, it remains difficult to know what, if any, impact obesity may have on the clinical course of disease.

Does obesity impact IBD treatment or cause differences in clinical response?

There is data to suggest that obesity may indeed impact the pharmacokinetics of our available biologic therapies, namely absorption, volume of distribution and drug clearance. The two most common means by which IBD therapies are administered are subcutaneously or intravenously. Additionally, some of these drugs are weight-based, while others are fixed doses.

Understanding that obesity may alter the pharmacokinetics of these drugs raises questions about whether the administration of weight-based intravenous therapies such as infliximab may perform better in patients with IBD who are obese. While there are some data to support this hypothesis, there are also contrasting data to suggest that the type of drug delivery does not impact obtainment of adequate drug levels and that there must be something intrinsic to obesity that is playing a role in the reduced response to therapy.

This hypothesis largely stems from the idea that obesity itself is considered a chronic low-grade inflammatory state. Adipose tissue is not biologically inert, but rather is responsible for producing a myriad of cytokines, including TNF-alpha, one of the main inflammatory cytokines implicated in the pathogenesis of active IBD. Therefore, it's possible that the higher volumes of adipose tissue present in patients who are obese create a larger burden of inflammatory cytokines to target, as compared with those found in patients who are not obese.

In the end, while there is some data to suggest that obesity alters the pharmacokinetics of our currently available medications, it remains a bit unclear to what degree it may impact response to therapy.

Do patients who are obese have differences in hospitalization or surgery outcomes?

Researchers have identified obesity as a risk factor for perioperative morbidity, with surgical site infections leading the list of associated complications. Patients who are obese also appear to be at increased risk of impaired wound healing, thromboembolic complications, lengthier hospital stays and increased need for short-term rehabilitation.

We know that obesity also makes surgery for IBD more challenging, particularly those requiring pelvic exposure, so these patients are at increased risk of short-term perioperative complications. These challenges include longer operative times and the need to convert laparoscopic procedures to open procedures. Stoma creation and pouch construction in patients who are obese are more difficult to perform and also appear to increase the risk of postoperative complications.

Performance of pouch construction in three-stage operations has helped reduce the risk of surgical complications in patients who are obese. Moreover, pursuing an ileal pouch-anal anastomosis in three stages also provides patients who are obese with the opportunity to achieve weight loss prior to pouch construction and restoration of continuity. In patients who underwent surgery in high-volume centers, longer term outcomes such as pouch function appear to be similar in patients who are obese and in patients who are not.

What limitations are present in studies published to date, and what additional research is needed to further clarify clinicians' understanding of this important topic?

It is clear that obesity is highly prevalent in the IBD population, but unfortunately there are large gaps in our understanding of the impact this has on the natural history and treatment outcomes. Not only is data pertaining to this area sparse, but it is plagued with several limitations. One of these limitations is the use of BMI, particularly at variable time points, as a surrogate measure of obesity.

One of the main hypotheses about the role of obesity in patients with IBD focuses on the differences between metabolic and biochemical properties associated with visceral adipose tissue (VAT) versus subcutaneous adipose tissue (SAT). This distinction may be important, and there are a few studies suggesting that VAT, rather than BMI, might carry prognostic value in predicting measures such as postoperative outcomes and disease recurrence in patients with Crohn's disease.

We also need studies addressing potential confounding factors such as smoking status, corticosteroid use or disease activity, which may impact weight status at a singular point in time.

To truly advance our understanding, future studies should incorporate prospective disease evaluation, improved control of confounding factors and assessment of obesity using measures that reflect VAT. Ideally, this research will make use of cross-sectional imaging studies such as computerized tomography, magnetic resonance imaging or dual-energy X-ray absorptiometry, all of which have been used in VAT assessment.

For more information

Johnson AM, et al. Impact of obesity on the management of inflammatory bowel disease. Gastroenterology and Hepatology. 2020;16:350.