New diverticulosis data challenge long-held beliefs

Not only is there no link between low-fiber diets and diverticulosis, but the incidence of diverticulitis is not nearly as common as was previously believed.

Those are the conclusions of two new studies in the December issue of Clinical Gastroenterology and Hepatology, both of which challenge long-held beliefs about the causes of these conditions.

In the first study, Dr. Anne F. Peery of the University of North Carolina at Chapel Hill, and her colleagues looked at 539 patients with colonic diverticula and 1,569 controls, all culled from the Vitamin D and Calcium Polyp Prevention Study, a double-blind, placebo-controlled trial of vitamin D and/or calcium for the prevention of colonic adenomas (doi:10.1016/j.cgh.2013.06.033).

Patients with a self-reported history of diverticulosis or diverticulitis were excluded, as were cases with a history of colon resection, inflammatory bowel disease, or familial history of colon cancer. Most cases (88%) had descending or sigmoid colon diverticula, and these patients were significantly older and more likely to be male than were the controls.

According to Dr. Peery and colleagues, there was no difference between cases and controls in terms of mean dietary fiber intake (14.8 g per day versus 15.3 g per day, P = .2) and reported supplemental fiber intake (5% versus 5%, P = .7).

Nor was there any significant link when investigators compared the highest quartile of fiber intake (mean, 25 g/day) to the lowest (mean, 8 g/day) (odds ratio = 0.96; 95% confidence interval, 0.71-1.30).

Finally, the investigators found no associations between dietary fiber intake by subtype (for instance, beans, grains, fruits, and vegetables) and diverticulosis.

"Forty years ago, Dr. Neil Painter popularized the hypothesis that inadequate dietary fiber intake and constipation were the cause of sigmoid diverticulosis," wrote Dr. Peery. However, "Although the fiber hypothesis is conceptually attractive and widely accepted, it has not been rigorously examined."

And while Dr. Peery’s data were based on a food frequency questionnaire – which could be subject to measurement bias – she added that "the mean total fiber intake in the highest quartile was 25 g, versus 8 g in the lowest.

"This wide range makes it unlikely that homogeneity of intake accounts for the null association of fiber with the presence of diverticula," she wrote.

A second study by Dr. Kamyar Shahedi of the University of California Los Angeles/Veteran’s Affairs Center for Outcomes Research and Education, also sought evidence for the commonly held belief that up to 25% of patients with diverticulosis will develop diverticulitis.

Dr. Shahedi and colleagues performed a retrospective survival analysis of 2,222 patients from the Veteran’s Affairs Greater Los Angeles Healthcare System with colonic diverticulosis and a median follow-up of 6.75 years (doi:10.1016/j.cgh.2013.06.020). Patients were excluded if they had any ICD-9 code for diverticulitis or documentation of diverticulitis in the medical record notes at any point before the index date of diverticulosis.

When the researchers looked only at imaging-confirmed or surgical specimen–confirmed cases, just 23 patients (1%) developed acute diverticulitis during the study period, Dr. Shahedi found. This jumped to 95 patients (4.3%) when clinical diagnoses were also used, for an incidence of 6 cases per 1,000 patient years.

Looking at predictors for progression, the authors found that only age was related to the development of diverticulitis, with every year of age at diverticulosis detection conferring a 2.4% lower hazard of developing diverticulitis.

According to the authors, the "widely cited figures" that up to a quarter of patients with diverticulosis will develop acute diverticulitis is based on data collected before the time of routine colon screening. "Therefore, the true denominator of individuals harboring diverticulosis was not accounted for in these calculations," they concluded.

And while their retrospective study does leave room for the possibility that cases were missed, "Future series or patient registries may better standardize the definition of diverticulitis in a prospective cohort," wrote the investigators.

In the meantime, prevalence data such as these "may help to reframe discussions with patients regarding their probability of developing clinically significant diverticulitis."

However, even as these two findings change the way providers counsel patients about the cause and impact of diverticula, a third study, also in December’s issue of Clinical Gastroenterology and Hepatology, adds another wrinkle: Patients who do develop diverticulitis are at increased risk for a diagnosis of irritable bowel syndrome later on.

Dr. Erica Cohen of the VA Greater Los Angeles Healthcare System, and colleagues looked at 1,105 chart-confirmed cases of diverticulitis, identified retrospectively from the same dataset used by Dr. Shahedi (doi:10.1016/j.cgh.2013.03.007).

All cases were matched with controls seen on the same day, the mean follow-up period was 6.3 years, and patients with pre-existing IBS or functional bowel diagnoses were excluded from the study.

The primary outcome was a new IBS diagnosis after the index diverticulitis attack (for cases) or enrollment date (for controls). Ultimately, Dr. Cohen found 24 cases of newly diagnosed IBS during the study period: 20 among diverticulitis cases, and 4 among controls. That translated to a hazard ratio of 4.7 among cases compared with controls, even after adjustment for age, sex, ethnicity, race, inpatient versus outpatient status, and comorbidity score (95% CI, 1.6 –14.0; P = .006).

Dr. Cohen offered several possible explanations for the association between diverticulitis and new diagnosis of IBS.

"Inflammation may alter gastrointestinal reflexes, amplify visceral sensitivity, render the bowel more susceptible to negative effects of microbiota, and alter motility in IBS," she said.

"Another putative mechanism of chronic diverticular disease involves shifts in intestinal microbiota leading to chronic inflammation, similar to theoretical models of IBS," Dr. Cohen said.

"Future research should identify demographic and clinical predictors of post-diverticulitis irritable bowel syndrome and evaluate its incidence in prospective studies to better determine whether the link is causal or merely associative," she concluded.

Finally, a fourth study could help researchers reduce the risk of the painful inflammatory condition: Among diverticulosis patients, higher levels of serum vitamin D were associated significantly with a lower risk of diverticulitis.

In her analysis, also published in the December issue of Clinical Gastroenterology and Hepatology, Dr. Lillias H. Maguire and colleagues identified 9,116 diverticulosis patients and 922 diverticulitis patients from the Partners Healthcare Research Patient Data Registry (doi:10.1016/j.cgh.2013.07.035). All patients had at least one prediagnostic serum vitamin D level on record between 1993 and 2012.

Dr. Maguire of Massachusetts General Hospital, Boston, found that patients with uncomplicated diverticulosis had mean levels of 29.1 ng/mL, versus 25.3 ng/mL among the diverticulitis patients (P less than .0001).

A sensitivity analysis that compared the mean prediagnostic values between cases and controls who had more than one reported vitamin D level yielded similarly significant results: The mean vitamin D level of uncomplicated diverticulosis was 33.0 ng/mL, compared with 28.1 ng/mL for acute diverticulitis patients (P less than .0001), 28.8 ng/mL for complicated diverticulitis patients (P = .002), 23.9 ng/mL for surgical diverticulitis cases (P less than .0001), and 25.5 ng/mL for recurrent diverticulitis patients (P less than .0001).

Indeed, "Compared with patients with acute diverticulitis without other sequelae, patients in the subgroups who developed abscess, required surgery, or had recurrent attacks were observed to have lower prediagnostic levels of vitamin D."

These differences between diverticulitis subgroups did not reach significance except in the cohort of patients who required surgery, who had the lowest levels of all.

"Taken together with prior studies showing an inverse association of 25(OH)D and risk of colonic cancer and inflammatory bowel disease, these results highlight the potential importance of vitamin D in the maintenance of colonic health," the investigators wrote.

"Additional studies in cohorts with more detailed information on potential confounders of this association are warranted," they added.

Dr. Peery, whose study looked at fiber intake among diverticulosis patients, and her collaborators reported having no disclosures, and stated that they received funding from the National Institutes of Health.

Dr. Shahedi, who assessed the incidence of diverticulitis, disclosed that three coinvestigators are employees of Shire Pharmaceuticals, which sponsored their study. Other investigators disclosed ties to Amgen and Ironwood Pharmaceuticals.

Dr. Cohen’s coinvestigators, who studied the prevalence of IBS following diverticulitis, disclosed ties to Ironwood Pharmaceuticals, Prometheus, Takeda Pharmaceuticals, Amgen, Ritter Pharmaceuticals, and Shire. Two investigators were employees of Shire, which funded the research.

Finally, the coinvestigators of Dr. Maguire, who looked at vitamin D levels, reported ties to Shire, Bayer Health, Pfizer, Millennium Pharmaceuticals, and Pozen. They were funded by grants from the American College of Gastroenterology as well as the National Institutes of Health.

Not only is there no link between low-fiber diets and diverticulosis, but the incidence of diverticulitis is not nearly as common as was previously believed.

Those are the conclusions of two new studies in the December issue of Clinical Gastroenterology and Hepatology, both of which challenge long-held beliefs about the causes of these conditions.

In the first study, Dr. Anne F. Peery of the University of North Carolina at Chapel Hill, and her colleagues looked at 539 patients with colonic diverticula and 1,569 controls, all culled from the Vitamin D and Calcium Polyp Prevention Study, a double-blind, placebo-controlled trial of vitamin D and/or calcium for the prevention of colonic adenomas (doi:10.1016/j.cgh.2013.06.033).

Patients with a self-reported history of diverticulosis or diverticulitis were excluded, as were cases with a history of colon resection, inflammatory bowel disease, or familial history of colon cancer. Most cases (88%) had descending or sigmoid colon diverticula, and these patients were significantly older and more likely to be male than were the controls.

According to Dr. Peery and colleagues, there was no difference between cases and controls in terms of mean dietary fiber intake (14.8 g per day versus 15.3 g per day, P = .2) and reported supplemental fiber intake (5% versus 5%, P = .7).

Nor was there any significant link when investigators compared the highest quartile of fiber intake (mean, 25 g/day) to the lowest (mean, 8 g/day) (odds ratio = 0.96; 95% confidence interval, 0.71-1.30).

Finally, the investigators found no associations between dietary fiber intake by subtype (for instance, beans, grains, fruits, and vegetables) and diverticulosis.

"Forty years ago, Dr. Neil Painter popularized the hypothesis that inadequate dietary fiber intake and constipation were the cause of sigmoid diverticulosis," wrote Dr. Peery. However, "Although the fiber hypothesis is conceptually attractive and widely accepted, it has not been rigorously examined."

And while Dr. Peery’s data were based on a food frequency questionnaire – which could be subject to measurement bias – she added that "the mean total fiber intake in the highest quartile was 25 g, versus 8 g in the lowest.

"This wide range makes it unlikely that homogeneity of intake accounts for the null association of fiber with the presence of diverticula," she wrote.

A second study by Dr. Kamyar Shahedi of the University of California Los Angeles/Veteran’s Affairs Center for Outcomes Research and Education, also sought evidence for the commonly held belief that up to 25% of patients with diverticulosis will develop diverticulitis.

Dr. Shahedi and colleagues performed a retrospective survival analysis of 2,222 patients from the Veteran’s Affairs Greater Los Angeles Healthcare System with colonic diverticulosis and a median follow-up of 6.75 years (doi:10.1016/j.cgh.2013.06.020). Patients were excluded if they had any ICD-9 code for diverticulitis or documentation of diverticulitis in the medical record notes at any point before the index date of diverticulosis.

When the researchers looked only at imaging-confirmed or surgical specimen–confirmed cases, just 23 patients (1%) developed acute diverticulitis during the study period, Dr. Shahedi found. This jumped to 95 patients (4.3%) when clinical diagnoses were also used, for an incidence of 6 cases per 1,000 patient years.

Looking at predictors for progression, the authors found that only age was related to the development of diverticulitis, with every year of age at diverticulosis detection conferring a 2.4% lower hazard of developing diverticulitis.

According to the authors, the "widely cited figures" that up to a quarter of patients with diverticulosis will develop acute diverticulitis is based on data collected before the time of routine colon screening. "Therefore, the true denominator of individuals harboring diverticulosis was not accounted for in these calculations," they concluded.

And while their retrospective study does leave room for the possibility that cases were missed, "Future series or patient registries may better standardize the definition of diverticulitis in a prospective cohort," wrote the investigators.

In the meantime, prevalence data such as these "may help to reframe discussions with patients regarding their probability of developing clinically significant diverticulitis."

However, even as these two findings change the way providers counsel patients about the cause and impact of diverticula, a third study, also in December’s issue of Clinical Gastroenterology and Hepatology, adds another wrinkle: Patients who do develop diverticulitis are at increased risk for a diagnosis of irritable bowel syndrome later on.

Dr. Erica Cohen of the VA Greater Los Angeles Healthcare System, and colleagues looked at 1,105 chart-confirmed cases of diverticulitis, identified retrospectively from the same dataset used by Dr. Shahedi (doi:10.1016/j.cgh.2013.03.007).

All cases were matched with controls seen on the same day, the mean follow-up period was 6.3 years, and patients with pre-existing IBS or functional bowel diagnoses were excluded from the study.

The primary outcome was a new IBS diagnosis after the index diverticulitis attack (for cases) or enrollment date (for controls). Ultimately, Dr. Cohen found 24 cases of newly diagnosed IBS during the study period: 20 among diverticulitis cases, and 4 among controls. That translated to a hazard ratio of 4.7 among cases compared with controls, even after adjustment for age, sex, ethnicity, race, inpatient versus outpatient status, and comorbidity score (95% CI, 1.6 –14.0; P = .006).

Dr. Cohen offered several possible explanations for the association between diverticulitis and new diagnosis of IBS.

"Inflammation may alter gastrointestinal reflexes, amplify visceral sensitivity, render the bowel more susceptible to negative effects of microbiota, and alter motility in IBS," she said.

"Another putative mechanism of chronic diverticular disease involves shifts in intestinal microbiota leading to chronic inflammation, similar to theoretical models of IBS," Dr. Cohen said.

"Future research should identify demographic and clinical predictors of post-diverticulitis irritable bowel syndrome and evaluate its incidence in prospective studies to better determine whether the link is causal or merely associative," she concluded.

Finally, a fourth study could help researchers reduce the risk of the painful inflammatory condition: Among diverticulosis patients, higher levels of serum vitamin D were associated significantly with a lower risk of diverticulitis.

In her analysis, also published in the December issue of Clinical Gastroenterology and Hepatology, Dr. Lillias H. Maguire and colleagues identified 9,116 diverticulosis patients and 922 diverticulitis patients from the Partners Healthcare Research Patient Data Registry (doi:10.1016/j.cgh.2013.07.035). All patients had at least one prediagnostic serum vitamin D level on record between 1993 and 2012.

Dr. Maguire of Massachusetts General Hospital, Boston, found that patients with uncomplicated diverticulosis had mean levels of 29.1 ng/mL, versus 25.3 ng/mL among the diverticulitis patients (P less than .0001).

A sensitivity analysis that compared the mean prediagnostic values between cases and controls who had more than one reported vitamin D level yielded similarly significant results: The mean vitamin D level of uncomplicated diverticulosis was 33.0 ng/mL, compared with 28.1 ng/mL for acute diverticulitis patients (P less than .0001), 28.8 ng/mL for complicated diverticulitis patients (P = .002), 23.9 ng/mL for surgical diverticulitis cases (P less than .0001), and 25.5 ng/mL for recurrent diverticulitis patients (P less than .0001).

Indeed, "Compared with patients with acute diverticulitis without other sequelae, patients in the subgroups who developed abscess, required surgery, or had recurrent attacks were observed to have lower prediagnostic levels of vitamin D."

These differences between diverticulitis subgroups did not reach significance except in the cohort of patients who required surgery, who had the lowest levels of all.

"Taken together with prior studies showing an inverse association of 25(OH)D and risk of colonic cancer and inflammatory bowel disease, these results highlight the potential importance of vitamin D in the maintenance of colonic health," the investigators wrote.

"Additional studies in cohorts with more detailed information on potential confounders of this association are warranted," they added.

Dr. Peery, whose study looked at fiber intake among diverticulosis patients, and her collaborators reported having no disclosures, and stated that they received funding from the National Institutes of Health.

Dr. Shahedi, who assessed the incidence of diverticulitis, disclosed that three coinvestigators are employees of Shire Pharmaceuticals, which sponsored their study. Other investigators disclosed ties to Amgen and Ironwood Pharmaceuticals.

Dr. Cohen’s coinvestigators, who studied the prevalence of IBS following diverticulitis, disclosed ties to Ironwood Pharmaceuticals, Prometheus, Takeda Pharmaceuticals, Amgen, Ritter Pharmaceuticals, and Shire. Two investigators were employees of Shire, which funded the research.

Finally, the coinvestigators of Dr. Maguire, who looked at vitamin D levels, reported ties to Shire, Bayer Health, Pfizer, Millennium Pharmaceuticals, and Pozen. They were funded by grants from the American College of Gastroenterology as well as the National Institutes of Health.

Not only is there no link between low-fiber diets and diverticulosis, but the incidence of diverticulitis is not nearly as common as was previously believed.

Those are the conclusions of two new studies in the December issue of Clinical Gastroenterology and Hepatology, both of which challenge long-held beliefs about the causes of these conditions.

In the first study, Dr. Anne F. Peery of the University of North Carolina at Chapel Hill, and her colleagues looked at 539 patients with colonic diverticula and 1,569 controls, all culled from the Vitamin D and Calcium Polyp Prevention Study, a double-blind, placebo-controlled trial of vitamin D and/or calcium for the prevention of colonic adenomas (doi:10.1016/j.cgh.2013.06.033).

Patients with a self-reported history of diverticulosis or diverticulitis were excluded, as were cases with a history of colon resection, inflammatory bowel disease, or familial history of colon cancer. Most cases (88%) had descending or sigmoid colon diverticula, and these patients were significantly older and more likely to be male than were the controls.

According to Dr. Peery and colleagues, there was no difference between cases and controls in terms of mean dietary fiber intake (14.8 g per day versus 15.3 g per day, P = .2) and reported supplemental fiber intake (5% versus 5%, P = .7).

Nor was there any significant link when investigators compared the highest quartile of fiber intake (mean, 25 g/day) to the lowest (mean, 8 g/day) (odds ratio = 0.96; 95% confidence interval, 0.71-1.30).

Finally, the investigators found no associations between dietary fiber intake by subtype (for instance, beans, grains, fruits, and vegetables) and diverticulosis.

"Forty years ago, Dr. Neil Painter popularized the hypothesis that inadequate dietary fiber intake and constipation were the cause of sigmoid diverticulosis," wrote Dr. Peery. However, "Although the fiber hypothesis is conceptually attractive and widely accepted, it has not been rigorously examined."

And while Dr. Peery’s data were based on a food frequency questionnaire – which could be subject to measurement bias – she added that "the mean total fiber intake in the highest quartile was 25 g, versus 8 g in the lowest.

"This wide range makes it unlikely that homogeneity of intake accounts for the null association of fiber with the presence of diverticula," she wrote.

A second study by Dr. Kamyar Shahedi of the University of California Los Angeles/Veteran’s Affairs Center for Outcomes Research and Education, also sought evidence for the commonly held belief that up to 25% of patients with diverticulosis will develop diverticulitis.

Dr. Shahedi and colleagues performed a retrospective survival analysis of 2,222 patients from the Veteran’s Affairs Greater Los Angeles Healthcare System with colonic diverticulosis and a median follow-up of 6.75 years (doi:10.1016/j.cgh.2013.06.020). Patients were excluded if they had any ICD-9 code for diverticulitis or documentation of diverticulitis in the medical record notes at any point before the index date of diverticulosis.

When the researchers looked only at imaging-confirmed or surgical specimen–confirmed cases, just 23 patients (1%) developed acute diverticulitis during the study period, Dr. Shahedi found. This jumped to 95 patients (4.3%) when clinical diagnoses were also used, for an incidence of 6 cases per 1,000 patient years.

Looking at predictors for progression, the authors found that only age was related to the development of diverticulitis, with every year of age at diverticulosis detection conferring a 2.4% lower hazard of developing diverticulitis.

According to the authors, the "widely cited figures" that up to a quarter of patients with diverticulosis will develop acute diverticulitis is based on data collected before the time of routine colon screening. "Therefore, the true denominator of individuals harboring diverticulosis was not accounted for in these calculations," they concluded.

And while their retrospective study does leave room for the possibility that cases were missed, "Future series or patient registries may better standardize the definition of diverticulitis in a prospective cohort," wrote the investigators.

In the meantime, prevalence data such as these "may help to reframe discussions with patients regarding their probability of developing clinically significant diverticulitis."

However, even as these two findings change the way providers counsel patients about the cause and impact of diverticula, a third study, also in December’s issue of Clinical Gastroenterology and Hepatology, adds another wrinkle: Patients who do develop diverticulitis are at increased risk for a diagnosis of irritable bowel syndrome later on.

Dr. Erica Cohen of the VA Greater Los Angeles Healthcare System, and colleagues looked at 1,105 chart-confirmed cases of diverticulitis, identified retrospectively from the same dataset used by Dr. Shahedi (doi:10.1016/j.cgh.2013.03.007).

All cases were matched with controls seen on the same day, the mean follow-up period was 6.3 years, and patients with pre-existing IBS or functional bowel diagnoses were excluded from the study.

The primary outcome was a new IBS diagnosis after the index diverticulitis attack (for cases) or enrollment date (for controls). Ultimately, Dr. Cohen found 24 cases of newly diagnosed IBS during the study period: 20 among diverticulitis cases, and 4 among controls. That translated to a hazard ratio of 4.7 among cases compared with controls, even after adjustment for age, sex, ethnicity, race, inpatient versus outpatient status, and comorbidity score (95% CI, 1.6 –14.0; P = .006).

Dr. Cohen offered several possible explanations for the association between diverticulitis and new diagnosis of IBS.

"Inflammation may alter gastrointestinal reflexes, amplify visceral sensitivity, render the bowel more susceptible to negative effects of microbiota, and alter motility in IBS," she said.

"Another putative mechanism of chronic diverticular disease involves shifts in intestinal microbiota leading to chronic inflammation, similar to theoretical models of IBS," Dr. Cohen said.

"Future research should identify demographic and clinical predictors of post-diverticulitis irritable bowel syndrome and evaluate its incidence in prospective studies to better determine whether the link is causal or merely associative," she concluded.

Finally, a fourth study could help researchers reduce the risk of the painful inflammatory condition: Among diverticulosis patients, higher levels of serum vitamin D were associated significantly with a lower risk of diverticulitis.

In her analysis, also published in the December issue of Clinical Gastroenterology and Hepatology, Dr. Lillias H. Maguire and colleagues identified 9,116 diverticulosis patients and 922 diverticulitis patients from the Partners Healthcare Research Patient Data Registry (doi:10.1016/j.cgh.2013.07.035). All patients had at least one prediagnostic serum vitamin D level on record between 1993 and 2012.

Dr. Maguire of Massachusetts General Hospital, Boston, found that patients with uncomplicated diverticulosis had mean levels of 29.1 ng/mL, versus 25.3 ng/mL among the diverticulitis patients (P less than .0001).

A sensitivity analysis that compared the mean prediagnostic values between cases and controls who had more than one reported vitamin D level yielded similarly significant results: The mean vitamin D level of uncomplicated diverticulosis was 33.0 ng/mL, compared with 28.1 ng/mL for acute diverticulitis patients (P less than .0001), 28.8 ng/mL for complicated diverticulitis patients (P = .002), 23.9 ng/mL for surgical diverticulitis cases (P less than .0001), and 25.5 ng/mL for recurrent diverticulitis patients (P less than .0001).

Indeed, "Compared with patients with acute diverticulitis without other sequelae, patients in the subgroups who developed abscess, required surgery, or had recurrent attacks were observed to have lower prediagnostic levels of vitamin D."

These differences between diverticulitis subgroups did not reach significance except in the cohort of patients who required surgery, who had the lowest levels of all.

"Taken together with prior studies showing an inverse association of 25(OH)D and risk of colonic cancer and inflammatory bowel disease, these results highlight the potential importance of vitamin D in the maintenance of colonic health," the investigators wrote.

"Additional studies in cohorts with more detailed information on potential confounders of this association are warranted," they added.

Dr. Peery, whose study looked at fiber intake among diverticulosis patients, and her collaborators reported having no disclosures, and stated that they received funding from the National Institutes of Health.

Dr. Shahedi, who assessed the incidence of diverticulitis, disclosed that three coinvestigators are employees of Shire Pharmaceuticals, which sponsored their study. Other investigators disclosed ties to Amgen and Ironwood Pharmaceuticals.

Dr. Cohen’s coinvestigators, who studied the prevalence of IBS following diverticulitis, disclosed ties to Ironwood Pharmaceuticals, Prometheus, Takeda Pharmaceuticals, Amgen, Ritter Pharmaceuticals, and Shire. Two investigators were employees of Shire, which funded the research.

Finally, the coinvestigators of Dr. Maguire, who looked at vitamin D levels, reported ties to Shire, Bayer Health, Pfizer, Millennium Pharmaceuticals, and Pozen. They were funded by grants from the American College of Gastroenterology as well as the National Institutes of Health.