Interaction of obesity and inflammatory bowel disease

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obesity 74 endocrinologydiseases
hyperglycemia 1 endocrinologydiseases
hyperinsulinemia 1 endocrinologydiseases

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hyperglycemia 17486 to healthy controls; curiously, this same study demonstrated that hyperinsulinemia in the absence of hyperglycemia was independently associated with a higher likelihood of clinical remission in IBD patients (in tandem
hyperinsulinemia 17451 active and inactive IBD compared to healthy controls; curiously, this same study demonstrated that hyperinsulinemia in the absence of hyperglycemia was independently associated with a higher likelihood of clinical remission
obesity 55 Title: World Journal of GastroenterologyInteraction of obesity and inflammatory bowel diseaseJason W HarperTimothy L ZismanPublication date (ppub): 9/2016Publication
obesity 629 related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between
obesity 783 suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions.
obesity 1046 pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging
obesity 1239 Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review
obesity 1384 potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and
obesity 1461 discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management.Core tip: Epidemiologic studies have shown a parallel
obesity 1603 implications for management.Core tip: Epidemiologic studies have shown a parallel rise in the prevalence of obesity and immune-mediated conditions, including inflammatory bowel disease (IBD). This association may be
obesity 1876 their effect through changes in the intestinal microbiota. Several lines of evidence demonstrate that obesity is a pro-inflammatory condition that impacts the incidence, disease course and response to therapy in
obesity 2053 course and response to therapy in patients with IBD. Exploring the mechanisms of interaction between obesity and IBD advances our understanding of IBD and opens up a potential role for weight loss and weight maintenance
obesity 2908 increases over time demonstrated in both developed and developing nations[[2]]. The global cost of treating obesity and its resultant health complications may be as much as $2 trillion (US)[[3]]. Although obesity was
obesity 3005 treating obesity and its resultant health complications may be as much as $2 trillion (US)[[3]]. Although obesity was once considered uncommon in IBD, the prevalence of obesity in IBD has risen in parallel with the
obesity 3068 much as $2 trillion (US)[[3]]. Although obesity was once considered uncommon in IBD, the prevalence of obesity in IBD has risen in parallel with the general population. Several lines of evidence support a biologically
obesity 3280 biologically plausible connection between adiposity and IBD (Figure 1). Understanding the interaction between obesity and IBD with regard to disease pathogenesis, phenotypic disease expression and response to therapy has
obesity 3470 response to therapy has important implications for management.Figure 1Proposed etiologic links between obesity and inflammatory bowel disease.EPIDEMIOLOGY OF IBD AND OBESITYTemporal trends have demonstrated an increase
obesity 4277 fat/protein and decreased dietary fiber intake[[9]-[11]]. Given the rising incidence of both IBD and obesity - as well as the interplay between some of the aforementioned risk factors common to both conditions-an
obesity 4555 postulated. To date there is a relative paucity of population-level studies reporting the prevalence of obesity among individuals with IBD, but reports from various IBD cohorts in both pediatric and adult populations
obesity 5278 of increasing BMI among study participants throughout this period of time[[16]].As to whether or not obesity - as reflected by the body mass index-is an intrinsic risk factor for the development of de novo IBD,
obesity 5945 in adults, compared to an older (age 50-70 years) non-IBD control cohort, suggested a higher rate of obesity at diagnosis in the IBD patients (OR = 2.0, P = 0.01)[[18]]. More recently published data from the Nurses’
obesity 6440 Crohn’s disease in this cohort. No such relationship between BMI or anthropometric measurements of obesity was seen with incident UC in this same study[[19]]. Another cohort of women recruited in Denmark also
obesity 7163 distribution in the EPIC cohort. If there is in fact an increased risk of developing IBD intrinsic to obesity , this risk may interact with age and sex. Adding to the biologic plausibility of an etiologic link between
obesity 7334 biologic plausibility of an etiologic link between adiposity and IBD, other studies have demonstrated that obesity is associated with an increased risk of developing other autoimmune conditions such as rheumatoid arthritis
obesity 7629 IBD[[21],[22]].RELATIONSHIP BETWEEN OBESITY AND IBD OUTCOMESThere are mixed data regarding the impact of obesity on IBD-related health outcomes (Table 1). Co-morbid obesity has been linked to an earlier time to first
obesity 7689 are mixed data regarding the impact of obesity on IBD-related health outcomes (Table 1). Co-morbid obesity has been linked to an earlier time to first surgery among patients with Crohn’s disease in one retrospective
obesity 8377 need for surgery, hospitalization or medication escalation across BMI categories, after adjustment for obesity -related health conditions such as hypertension or diabetes. However, increased BMI was associated with
obesity 10272 need for surgery and corticosteroid use did not differ between groups[[27]].Table 1Clinical impact of obesity on inflammatory bowel diseaseMedical therapySurgical therapyNatural history and disease complicationsDecreased
obesity 11147 made about the potential interaction between diabetes and inflammatory bowel disease independent of obesity , given the strong and well-described association between obesity and type 2 diabetes. Individuals with
obesity 11212 inflammatory bowel disease independent of obesity, given the strong and well-described association between obesity and type 2 diabetes. Individuals with IBD (UC specifically) may be at higher risk of developing de novo
obesity 11803 marker of adiposity, and as yet, we have much less data about the interaction between other markers of obesity , such as volumetric analysis of visceral fat, and IBD outcomes. One small retrospective study of individuals
obesity 12348 aforementioned finding of less penetrating disease among obese IBD patients when solely BMI is used to define obesity [[32]]. Prospective data are lacking with regard to the potential interaction between obesity and IBD
obesity 12441 define obesity[[32]]. Prospective data are lacking with regard to the potential interaction between obesity and IBD complications that are independently associated with both conditions, such as venous thromboembolism;
obesity 12724 and, perhaps most importantly, colorectal cancer[[33]-[36]]. Also confounding the relationship between obesity and IBD outcomes is the observation that increased visceral adiposity may be associated with a higher
obesity 13315 surgery.DEFINITION OF OBESITYOne of the ongoing challenges in trying to elucidate the interaction between obesity and health outcomes has been the lack of consensus regarding a standardized definition of obesity. For
obesity 13413 between obesity and health outcomes has been the lack of consensus regarding a standardized definition of obesity . For its ease of use, the body mass index (BMI), a simple adjusted ratio of weight to height, has been
obesity 13562 (BMI), a simple adjusted ratio of weight to height, has been used as the operational definition of obesity when it exceeds 30 kg/m2. As an isolated measure, the BMI does predict broad health outcomes such as
obesity 13715 measure, the BMI does predict broad health outcomes such as all-cause mortality at higher categories of obesity (such as BMI > 35 or 40 kg/m2), but performs poorly (and may indicate lower all-cause mortality) when
obesity 14012 25 kg/m2)[[38],[39]]. Multiple studies have demonstrated that various anthropometric measurements of obesity - such as the waist-to-hip circumference ratio or volumetric analysis of abdominal fat via cross-sectional
obesity 14274 of adverse health outcomes[[40]-[42]]. A glaring deficit in the current literature regarding IBD and obesity has been the general reliance on the BMI as the sole marker of obesity, and lack of validation of the
obesity 14345 literature regarding IBD and obesity has been the general reliance on the BMI as the sole marker of obesity , and lack of validation of the standard BMI categories of overweight or obesity as clinically relevant
obesity 14425 the sole marker of obesity, and lack of validation of the standard BMI categories of overweight or obesity as clinically relevant cutoffs in IBD. As addressed in this review in later sections, it may be that
obesity 14656 is more clinically significant than overall body size. As such, incorporation of multiple domains of obesity to reflect the differences between health outcomes and body fat distribution, would help elucidate the
obesity 14782 differences between health outcomes and body fat distribution, would help elucidate the interaction of obesity and IBD by minimizing the confounding effect of individuals with elevated lean body mass who happen
obesity 15613 some intriguing points are worth reviewing.Table 2Immunologic effect of adipokinesAdipokineLevels in obesity Immunologic effectsOverall effectAdiponectinDecreasedDecreases TNF-α, IFNγ, IL-6Anti-inflammatoryInhibits
obesity 22049 health. More recent attention has been paid to the possible links between the microbiome and human obesity . The gut bacteria are capable of salvaging undigested foods to sources of calories usable by their human
obesity 22799 microbiome, leading to the selection of a more “obesogenic” bacteriologic profile; identification of obesity -attenuating bacterial species, and colonization of germ-free mice with those bacteria then leads to
obesity 23090 bacterial diversity-which is a state associated with IBD in general - also seem to be predisposed to obesity [[67],[68]]. Furthermore, specific bacteria shown to exert an anti-inflammatory effect on the gut-such
obesity 23837 ripe area for future investigation.OBESITY AND IBD PHARMACOLOGYDespite the increasing prevalence of obesity in IBD, and the seemingly logical differences in pharmacokinetics that may be expected in obese vs non-obese
obesity 23984 differences in pharmacokinetics that may be expected in obese vs non-obese individuals, the influence of obesity on drug absorption, distribution, metabolism and excretion remain poorly understood, and discussion
obesity 24126 metabolism and excretion remain poorly understood, and discussion of the pharmacokinetic effects of obesity is beyond the scope of this review.If there are inter-individual differences in drug effect that are
obesity 24247 scope of this review.If there are inter-individual differences in drug effect that are impacted by obesity , pharmacodynamic differences likely account for the majority of these, perhaps by virtue of some of
obesity 24584 IBD-specific drugs. In fact, when considered by class, there are multiple studies that suggest that obesity does influence the efficacy of specific drugs commonly used to treat IBD. The following paragraphs will
obesity 25979 therapeutic or supra-therapeutic range[[71]].To date, there have been no studies addressing whether or not obesity influences the efficacy of methotrexate in treating IBD or in other similar autoimmune conditions, but
obesity 26144 or in other similar autoimmune conditions, but there have been multiple studies that have shown that obesity and obesity-related comorbidities increase the likelihood of developing derangement in hepatic transaminases
obesity 26156 similar autoimmune conditions, but there have been multiple studies that have shown that obesity and obesity -related comorbidities increase the likelihood of developing derangement in hepatic transaminases on
obesity 26587 in individuals with psoriasis treated with long-term low dose methotrexate[[74],[75]].The effects of obesity on the response to anti-TNF therapy have also been investigated, with several studies in both the IBD
obesity 32583 anti-TNF therapy among already overweight or obese IBD patients.No data are available about the effects of obesity on the efficacy of anti-integrin therapies in IBD. The major IBD clinical trials of natalizumab and
obesity 33562 induction dosing schedule.Finally, special mention should be made concerning the glucocorticoids (GCs) and obesity . Although the pharmacologic use of glucocorticoids is often blamed for unintended weight gain, the true
obesity 33955 in terms of the indication for GC therapy, the duration and dose of therapy, and the definition of obesity (e.g., changes in body weight or anthropometric changes) as an outcome measure. Looking at multiple
obesity 35055 prednisolone-treated patients compared to patients treated with ileal-release budesonide[[104]]. Whether obesity alters the efficacy or risks of GC therapy remains largely unknown; furthermore, whether accumulation
obesity 35691 infectious complications. Post-operative mortality, however, does not appear to be significantly affected by obesity after adjustment for co-morbid diseases[[105]]. Obesity has also been shown to be a risk factor for
obesity 35976 colorectal surgery in general[[106]].Specific to the IBD population, multiple lines of evidence suggest that obesity may negatively influence surgical outcomes, specifically when obesity is defined according to volumetric
obesity 36046 lines of evidence suggest that obesity may negatively influence surgical outcomes, specifically when obesity is defined according to volumetric analysis of fat distribution, rather than solely BMI. When looking
obesity 36191 analysis of fat distribution, rather than solely BMI. When looking solely at BMI categories to define obesity , a large retrospective surgical registry demonstrated a 10% higher rate of post-operative morbidity
obesity 37235 studies described a higher rate of post-operative complications among obese Crohn’s patients when obesity was defined by volumetric analysis, and in some cases, specifically noted that BMI stratification did
obesity 38200 stresses that occur after major abdominal surgery, and given that the most common metric to define obesity (i.e., BMI) does not reliably differentiate lean body mass from fat mass, and that losses in the former
obesity 39642 response to therapy. In patients with chronic plaque psoriasis-a condition in which an association with obesity is consistently demonstrated-multiple randomized controlled trials have shown a beneficial effect of
obesity 39968 cyclosporine and biologic (e.g., anti-TNF and anti-IL 12/23) therapy[[120]-[123]].For patients with morbid obesity (e.g., BMI > 40 kg/m2), particularly in those who have significant co-morbidities such as diabetes,
obesity 40223 reductions in all-cause mortality, and is more effective than routine medical care in the treatment of obesity -related complications such as diabetes[[124]-[126]]. There is a marked paucity of data in the literature
obesity 41355 given the extremely small number of such cases reported[[131]-[134]].CONCLUSIONThe prevalence of both obesity and IBD are increasing worldwide, and several lines of evidence suggest that these conditions may be
obesity 41828 activity in patients with immune-mediated diseases, including IBD. Studies reporting the influence of obesity on IBD disease course and response to medical therapy have described a mixed but largely detrimental
obesity 41978 medical therapy have described a mixed but largely detrimental impact. Lack of a standard definition of obesity hampers interpretation of the current literature, and establishing a clinically relevant measure of
obesity 42164 clinically relevant measure of adiposity is essential to advancing our understating of the interplay between obesity and IBD. Future studies are required to establish whether weight loss, either medical or surgical, is
obesity 42604 on BMI or other measures of adiposity, but such an approach would be premature currently.In summary, obesity has emerged as yet another important piece in the intricate puzzle of autoimmune diseases, such as IBD.
obesity 42806 such as IBD. Future studies that advance our understanding of the complex interactions between IBD and obesity are required to optimize patients’ health outcomes

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