In this large, prospective cohort of men, we found that BMI was independently associated with the risk of diverticulitis and diverticular bleeding. Positive associations were also found between weight gain, waist circumference and waist-to-hip ratio, further implicating body fat as a risk factor for diverticular complications. The strength of the relationships between obesity and each anthropometric measurement was similar after adjustment for other potential confounders, and when restricting the analysis to men who had undergone lower endoscopy, or who met the strictest definitions of outcome.
Few studies have evaluated the relationship between obesity and the risk of diverticulitis. Several retrospective case series noted the prevalence of obesity in patients presenting with diverticulitis.15–19
In these studies, 75% or more of patients were overweight or obese using a variety of criteria. Three of these studies were limited to patients younger than 40 years of age.15, 17, 19
In a case-control study, comparisons were made between 18 unmatched controls with uncomplicated diverticulosis, and 43 patients with diverticulitis.14
Body mass index was significantly higher in patients with recurrent diverticulitis or perforated diverticulitis compared to patients with uncomplicated disease or a single episode. None of these studies directly assessed the risk of diverticulitis associated with increasing BMI, or made adjustments for potential confounders. In a prior analysis of physical activity and diverticular disease using the Health Professionals Follow-up Study, we found a weak association between increasing BMI and symptomatic diverticular disease (diverticulitis, diverticular bleeding or nonspecific pain or bowel symptoms in the setting of diverticulosis).20
In a study of 112 cases from a prospective cardiovascular prevention trial in Sweden, BMI was significantly associated with symptomatic diverticular disease in men.21
Our study extends the findings of these previous studies in several important ways. First, detailed, prospective follow-up allowed us to control for important confounders that were not assessed in other cohorts or case series. These include dietary fiber, fat and red meat, and the use of non-steroidal anti-inflammatory drugs which are putative risk factors for diverticular complications,20, 26–31
and are also associated with obesity.36–38
Second, prior studies had limited sample sizes. In comparison to the prior Health Professionals Follow-up Study, the current study utilizes 12 additional years of follow-up. The large number of cases in the current study enabled us to evaluate diverticular bleeding, diverticulitis and diverticulosis without these complications as separate endpoints. This is important because diverticular bleeding and diverticulitis are distinct entities that likely evolve through different biologic pathways.22
Non-specific bowel symptoms are difficult to ascribe to diverticulosis, and may be more common in obese individuals in general.39, 40
Third, we were able to examine the influence of weight gain and fat distribution in addition to BMI. Visceral fat has proven to be particularly important in colon cancer and other gastrointestinal disorders.7, 23, 24, 41
Finally, previous studies (except the HPFS) have included only hospitalized patients, and may not be generalizable to the larger group of patients managed in the outpatient setting.42
The biological mechanisms by which obesity increases the risk of diverticular complications are unknown, and indeed factors underlying the progression from diverticulosis to diverticular complications remain poorly understood. However, obesity is plausibly linked to several factors thought to contribute to diverticular complications.43
Adipose tissue secretes a number of cytokines known to participate in local and generalized inflammation.10
Therefore, obesity may enhance or precipitate the inflammatory process in diverticulitis. In addition, recent reports indicate that intestinal microbes differ between obese and lean individuals.12
Alterations in the intestinal microflora are also postulated to play a role in the development of diverticulitis, although the exact nature of these alterations is unknown.11, 44
Obesity may influence diverticular bleeding through pathways that affect vascular integrity.22
Lastly, obesity may contribute to the development of diverticulosis. Obesity was not associated with asymptomatic diverticulosis in our study or in previous reports.4, 45
However, the confidence intervals in our analysis were relatively wide and random misclassification due to imperfect recall of endoscopy results could have biased the results towards the null.
We found that waist-to-hip ratio was significantly associated with diverticular complications after adjustment for BMI. In addition, the relationship with BMI was attenuated when adjusted for waist-to-hip ratio. Waist-to-hip ratio may be a better indicator of visceral fat than BMI, and visceral fat is more metabolically active than subcutaneous fat.46
Thus, fat distribution and its metabolic consequences may be important in the development of diverticular complications. Alternatively, this finding may reflect the imperfect nature of BMI as a measure of adiposity, as BMI does not differentiate fat from lean body mass. Therefore, waist-to-hip ratio may detect residual variation in overall obesity that is not accounted for by BMI.
Certain limitations of our study are worth noting. Self-reported diverticular disease and body measurements introduce the possibility of misclassification bias. However, study participants were health care professionals, review of 179 medical records endorsed the validity of self-reported diverticular disease, self-reported body measurements were verified in previous studies, and sensitivity analyses for the endpoint definitions revealed similar results. Residual confounding is another possible explanation for our findings, but we controlled for diet and physical activity (which had modest associations with the study endpoints, see ) and our results did not change appreciably. In addition, obese men may be more likely to be diagnosed with diverticular disease because of more frequent medical contact. However, the lack of an association between obesity and asymptomatic diverticulosis, and the similarity in the results when the analyses were restricted to men who had undergone a lower endoscopy diminish the likelihood of detection bias. Lastly, our study was limited to men over the age of 40 years. Nonetheless, diverticulosis is rare in young individuals, and males and females appear to be affected equally.45, 47
Appendix Table 1
Relative Risks of Variables Potentially Associated with Diverticulitis and Diverticular Bleeding
In summary, our results suggest that obesity, and perhaps central obesity in particular, is associated with an increased risk of diverticulitis and diverticular bleeding. The magnitude of the increased risk and the dose-response gradient was greater for diverticular bleeding than for diverticulitis. An association between body fat and diverticular complications has important clinical implications given the increasing prevalence of these disorders,48, 49
and the considerable risk of recurrent complications.50, 51
Indeed, with few known modifiable risk factors, current preventative measures rely heavily on prophylactic colectomy.47
The link between obesity and diverticular disease may also direct future studies aimed at uncovering mechanisms of disease.