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Obesity Increases the Risks of Diverticulitis and Diverticular Bleeding

  • Lisa L. Strate
    Correspondence
    Address requests for reprints to: Lisa L. Strate, MD, MPH, Harborview Medical Center, 325 Ninth Avenue, Box 359773, Seattle, Washington 98104. fax: (206) 744-8698
    Affiliations
    University of Washington School of Medicine, Seattle, Washington

    Division of Gastroenterology, Department of Medicine, Harborview Medical Center, Seattle, Washington
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  • Yan L. Liu
    Affiliations
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
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  • Walid H. Aldoori
    Affiliations
    Wyeth Consumer Healthcare, Inc, Mississauga, Ontario, Canada
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  • Sapna Syngal
    Affiliations
    Harvard Medical School, Boston, Massachusetts

    Division of Population Sciences, Dana Farber Cancer Institute, Boston, Massachusetts

    Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
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  • Edward L. Giovannucci
    Affiliations
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts

    Harvard Medical School, Boston, Massachusetts

    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts

    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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Published:September 26, 2008DOI:https://doi.org/10.1053/j.gastro.2008.09.025

      Background & Aims

      Studies of obesity and diverticular complications are limited. We assessed the relationship between body mass index (BMI), waist circumference, and waist-to-hip ratio and diverticulitis and diverticular bleeding.

      Methods

      A prospective cohort study of 47,228 male health professionals (40–75 years old) who were free of diverticular disease in 1986 (baseline) was performed. Men reporting newly diagnosed diverticular disease on biennial follow-up questionnaires were sent supplemental questionnaires. Weight was recorded every 2 years, and data on waist and hip circumferences were collected in 1987.

      Results

      We documented 801 incident cases of diverticulitis and 383 incident cases of diverticular bleeding during 18 years of follow-up. After adjustment for other risk factors, men with a BMI ≥30 kg/m2 had a relative risk (RR) of 1.78 (95% confidence interval [CI], 1.08–2.94) for diverticulitis and 3.19 (95% CI, 1.45–7.00) for diverticular bleeding compared with men with a BMI of <21 kg/m2. Men in the highest quintile of waist circumference, compared with those in the lowest, had a multivariable RR of 1.56 (95% CI, 1.18–2.07) for diverticulitis and 1.96 (95% CI, 1.30–2.97) for diverticular bleeding. Waist-to-hip ratio was also associated with the risk of diverticular complications when the highest and lowest quintiles were compared, with a multivariable RR of 1.62 (95% CI, 1.23–2.14) for diverticulitis and 1.91 (95% CI, 1.26–2.90) for diverticular bleeding. Adjustment for BMI did not change the associations seen for waist-to-hip ratio.

      Conclusions

      In this large prospective cohort, BMI, waist circumference, and waist-to-hip ratio significantly increased the risks of diverticulitis and diverticular bleeding.

      Abbreviations used in this paper:

      BMI (body mass index), CI (confidence interval), RR (relative risk)
      Diverticular disease is a common gastrointestinal indication for hospital admission and outpatient clinic visits.
      • Sandler R.S.
      • Everhart J.E.
      • Donowitz M.
      • et al.
      The burden of selected digestive diseases in the United States.
      • Shaheen N.J.
      • Hansen R.A.
      • Morgan D.R.
      • et al.
      The burden of gastrointestinal and liver diseases, 2006.
      It is estimated that 65% of adults will develop diverticulosis by 80 years of age, and 10%–30% of individuals with diverticulosis will experience complications including diverticulitis and diverticular bleeding.
      • Welch C.E.
      • Allen A.W.
      • Donaldson G.A.
      An appraisal of resection of the colon for diverticulitis of the sigmoid.
      • Horner J.L.
      Natural history of diverticulosis of the colon.
      Dietary fiber deficiency is regarded as a major risk factor for the development of diverticular disease. Indeed, the prevalence of diverticulosis rose dramatically following the introduction of refined cereal grains.
      • Painter N.S.
      Diverticular disease of the colon—a disease of the century.
      However, other dietary and lifestyle changes potentially related to diverticular disease parallel the adoption of a low-fiber diet, including obesity.
      Obesity is increasingly recognized as a risk factor for disease.
      Overweight, obesity, and health risk National Task Force on the Prevention and Treatment of Obesity.
      A number of digestive diseases have been associated with obesity, including cirrhosis, gallstone disease, gastroesophageal reflux disease, and cancers of the colon, esophagus, and pancreas.
      • El-Serag H.B.
      Obesity and disease of the esophagus and colon.
      • Ioannou G.N.
      • Weiss N.S.
      • Kowdley K.V.
      • et al.
      Is obesity a risk factor for cirrhosis-related death or hospitalization? A population-based cohort study.
      • Michaud D.S.
      • Giovannucci E.
      • Willett W.C.
      • et al.
      Physical activity, obesity, height, and the risk of pancreatic cancer.
      Some of the obesity-related mechanisms believed to play a role in these disorders may also influence diverticular complications, most notably the link between obesity and chronic inflammation.
      • Shoelson S.E.
      • Herrero L.
      • Naaz A.
      Obesity, inflammation, and insulin resistance.
      In addition, recently discovered differences in the intestinal flora of obese individuals may be relevant to diverticular disease.
      • Korzenik J.R.
      Case closed? Diverticulitis: epidemiology and fiber.
      • Ley R.E.
      • Turnbaugh P.J.
      • Klein S.
      • et al.
      Microbial ecology: human gut microbes associated with obesity.
      Several retrospective case series and a small case-control study have noted a preponderance of obesity in patients with diverticulitis, particularly patients younger than 40 years of age,
      • Dobbins C.
      • Defontgalland D.
      • Duthie G.
      • et al.
      The relationship of obesity to the complications of diverticular disease.
      • Konvolinka C.W.
      Acute diverticulitis under age forty.
      • Mader T.J.
      Acute diverticulitis in young adults.
      • Schauer P.R.
      • Ramos R.
      • Ghiatas A.A.
      • et al.
      Virulent diverticular disease in young obese men.
      • Schweitzer J.
      • Casillas R.A.
      • Collins J.C.
      Acute diverticulitis in the young adult is not “virulent”.
      • Zaidi E.
      • Daly B.
      CT and clinical features of acute diverticulitis in an urban U.S. population: rising frequency in young, obese adults.
      but could not directly examine the association with obesity. Two prospective cohort studies, a prior analysis of the first 6 years of the Health Professionals Follow-up Study and a Swedish male cohort, found positive associations between body mass index (BMI) and symptomatic diverticular disease (diverticulitis, diverticular bleeding, or nonspecific pain or bowel symptoms in the setting of diverticulosis).
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Prospective study of physical activity and the risk of symptomatic diverticular disease in men.
      • Rosemar A.
      • Angeras U.
      • Rosengren A.
      Body mass index and diverticular disease: a 28-year follow-up study in men.
      However, these studies were underpowered to examine diverticulitis, diverticular bleeding, and nonspecific symptoms as distinct clinical outcomes, although the pathophysiology of these complications and thus the effects of obesity are presumably quite different.
      • Meyers M.A.
      • Alonso D.R.
      • Gray G.F.
      • et al.
      Pathogenesis of bleeding colonic diverticulosis.
      In addition, in the Swedish study, important potential confounders including diet were not evaluated.
      • Rosemar A.
      • Angeras U.
      • Rosengren A.
      Body mass index and diverticular disease: a 28-year follow-up study in men.
      Previous studies have not considered other measures of central obesity that are particularly important in other gastrointestinal diseases.
      • El-Serag H.B.
      Obesity and disease of the esophagus and colon.
      • Corley D.A.
      • Kubo A.
      • Levin T.R.
      • et al.
      Abdominal obesity and body mass index as risk factors for Barrett's esophagus.
      • Giovannucci E.
      • Michaud D.
      The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas.
      We prospectively examined the associations between BMI, waist circumference, and waist-to-hip ratio and the risk of diverticulitis and diverticular bleeding using 18 years of follow-up data from a prospective cohort of male health professionals.

      Materials and Methods

       Study Population

      The study cohort consisted of 51,529 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists who have been prospectively followed up as part of the Health Professionals Follow-up Study. At baseline in 1986, participants were between the ages of 40 and 75 years and returned detailed questionnaires concerning diet, lifestyle, and medical history. Medical information has been updated biennially and dietary information every 4 years via self-administered questionnaires. The study was approved by the institutional review boards of the Harvard School of Public Health and Brigham and Women's Hospital.
      We excluded from the analysis men who reported at baseline a diagnosis of diverticulosis, diverticulitis or diverticular bleeding, cancer (except nonmelanoma skin cancer), or inflammatory bowel disease. In addition, men with average daily intakes outside the range of 800–4300 kcal and men who failed to return the food frequency questionnaire were excluded. The remaining baseline population included 47,228 men who were followed up from 1986 to 2004.

       Assessment of Diverticulitis and Diverticular Bleeding

      The primary study end points were incident diverticulitis and diverticular bleeding. Biennial follow-up questionnaires inquired about newly diagnosed diverticulosis or diverticulitis beginning in 1990. Participants reporting diverticular disease were sent a 5-question supplemental questionnaire addressing the following: (1) date of diagnosis, (2) procedures performed to confirm the diagnosis, (3) symptoms or tests leading to the detection of diverticular disease, (4) diet modification before the diagnosis, and (5) treatment received. Trained abstractors double entered the data, including information contained in free text.
      Individuals who reported a new diagnosis of diverticular disease were classified as having diverticulitis if they reported abdominal pain attributed to diverticular disease and one of the following: (1) complications of fistula, abscess, perforation, or obstruction; (2) treated with antibiotics, hospitalization, or surgery; (3) categorized as severe or acute, or presented with fever, required medication, or were evaluated with computed tomography. Diverticular bleeding was defined as rectal bleeding attributed to diverticular disease and one of the following: (1) requiring hospitalization, intravenous fluids, blood transfusions, angiography, nuclear medicine scanning, or surgery; (2) described as profuse bleeding; or (3) without other potential gastrointestinal, rectal, or anal sources in men whose bleeding was not evaluated as part of a routine endoscopy or barium enema examination. The first 2 criteria for each end point definition were used in sensitivity analyses for the end point definitions.
      To address the accuracy of self-report, 179 available medical records from men reporting diverticular disease on the 1990 and 1992 main study questionnaires were reviewed. Diverticular disease was confirmed in 97%. The overall concordance between the diagnosis in the medical record and the self-reported diagnosis based on our outcome definitions was 85%. In the remaining cases, 50% had a diagnosis of diverticulitis or diverticular bleeding on chart review but were classified as having uncomplicated disease based on self-report. The breakdown of self-reported diagnoses and the concordance with chart review was as follows: 91 cases of uncomplicated diverticulosis (51%) with 86% concordance, 77 cases of diverticulitis (43%) with 84% concordance, and 11 cases of diverticular bleeding (6%) with 73% concordance.

       Assessment of Anthropometric Measures

      BMI was calculated as weight (kg) per height (m) squared. Body weight was updated biennially, and height was reported at baseline. In addition, participants reported their weight at age 21 years on the baseline questionnaire. Waist and hip measurements were self-ascertained in 1987 and 1996. Illustrated instructions guided measurements of the waist at the level of the umbilicus and of the hips at the largest circumference while standing in close-fitting clothing. In a prior validation study, the correlation coefficients between the average of 2 technician measurements and self-reported measurements were 0.97 for weight, 0.95 for waist circumference, and 0.88 for hip circumference.
      • Rimm E.B.
      • Stampfer M.J.
      • Colditz G.A.
      • et al.
      Validity of self-reported waist and hip circumferences in men and women.

       Assessment of Other Potential Risk Factors

      Consumption of fiber, fat and red meat, physical activity, and use of nonsteroidal anti-inflammatory drugs and acetaminophen were also entertained as potential confounders. These have been shown to be risk factors for diverticular complications in this cohort and/or in other studies.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Prospective study of physical activity and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      A prospective study of diet and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rockett H.R.
      • et al.
      A prospective study of dietary fiber types and symptomatic diverticular disease in men.
      • Laine L.
      • Smith R.
      • Min K.
      • et al.
      Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs.
      • Manousos O.
      • Day N.E.
      • Tzonou A.
      • et al.
      Diet and other factors in the aetiology of diverticulosis: an epidemiological study in Greece.
      • Morris C.R.
      • Harvey I.M.
      • Stebbings W.S.
      • et al.
      Anti-inflammatory drugs, analgesics and the risk of perforated colonic diverticular disease.
      Nutritional information was assessed every 4 years from a food frequency questionnaire. Physical activity was assessed on biennial questionnaires and expressed in metabolic equivalent hours per week. Current regular use of nonsteroidal anti-inflammatory analgesics, including aspirin, and acetaminophen was assessed every 2 years. The validity and reproducibility of the dietary questionnaires and physical activity assessment have been shown previously.
      • Chasan-Taber S.
      • Rimm E.B.
      • Stampfer M.J.
      • et al.
      Reproducibility and validity of a self-administered physical activity questionnaire for male health professionals.
      • Rimm E.B.
      • Giovannucci E.L.
      • Stampfer M.J.
      • et al.
      Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals.

       Statistical Analysis

      We calculated person-years of follow-up from the date of return of the baseline questionnaire in 1986 to the date of the first diagnosis of diverticulosis or diverticular complications, the date of death, or December 31, 2004, whichever came first. Men who reported a new diagnosis of gastrointestinal cancer, diverticulosis, diverticulitis, diverticular bleeding, or inflammatory bowel disease were censored at the date of diagnosis. Information about potential risk factors, including body weight and size, was obtained before the diagnosis of diverticular disease.
      We divided BMI into 6 categories that encompass commonly used criteria for overweight and obesity.
      Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report National Institutes of Health.
      BMI at age 21 years was grouped in quintiles ranging from <21 kg/m2 to ≥25 kg/m2 due to the smaller number of men with large values of BMI at this age. Six categories of weight change since age 21 years were created (<5, 5–14.9, 15–24.9, 25–34.9, 35–44.9, and >45 lb). Quintiles were used to categorize waist circumference and waist-to-hip ratio. Variables were created for missing values of waist circumference and waist-to-hip ratio.
      Relative risks (RR) and corresponding 95% confidence intervals (CIs) were calculated for each end point using Cox proportional hazards models stratified by age in 1-year intervals and study period in 2-year intervals.
      • Cox D.R.
      Regression models and life tables.
      Men in the highest categories of each anthropometric measurement were compared with men in the lowest category. Multivariable RRs were calculated by simultaneously adjusting for other known or potential risk factors for diverticular disease, including total dietary fat (quintiles) and total dietary fiber (quintiles), consumption of red meat (quintiles), total caloric intake (quintiles), physical activity (quintiles), and current use of nonsteroidal anti-inflammatory medications (yes/no) and acetaminophen (yes/no).
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Prospective study of physical activity and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      A prospective study of diet and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rockett H.R.
      • et al.
      A prospective study of dietary fiber types and symptomatic diverticular disease in men.
      • Laine L.
      • Smith R.
      • Min K.
      • et al.
      Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs.
      • Manousos O.
      • Day N.E.
      • Tzonou A.
      • et al.
      Diet and other factors in the aetiology of diverticulosis: an epidemiological study in Greece.
      • Morris C.R.
      • Harvey I.M.
      • Stebbings W.S.
      • et al.
      Anti-inflammatory drugs, analgesics and the risk of perforated colonic diverticular disease.
      In addition, in the multivariable analyses of waist circumference, we adjusted for height in inches (<66, 66–67.9, 68–69.9, 70–71.9, and ≥72) to control for variation in waist due to body size.
      In the analyses, the most recent information available for each variable was used. We updated BMI, physical activity, and medication use biennially. Dietary covariates were updated every 4 years. Waist and hip measurements from 1987 were used in the analysis. For example, if a patient reported a study end point in 1989, data from the 1988 questionnaire would be used for BMI, physical activity, and medications and from the 1986 questionnaire for diet.
      We performed several secondary analyses. We restricted the main analyses to participants who had undergone a flexible sigmoidoscopy or colonoscopy to assess the possibility of detection bias. We also performed a sensitivity analysis for each end point by restricting the analysis to men meeting either of the first 2 end point criteria. For diverticulitis, these included abscess, fistula, perforation, obstruction, hospitalization, surgery, or antibiotics; for diverticular bleeding, these included profuse bleeding or bleeding requiring hospitalization, intravenous fluids, blood transfusions, angiography, nuclear medicine scanning, or surgery. Lastly, we investigated the relationship between body weight and asymptomatic diverticulosis. These analyses were limited to men who had undergone lower endoscopy due to the potential for detection bias with asymptomatic disease.
      Tests for linear trend were performed by treating the median value of each of the measurement categories as a continuous variable. We tested the proportional hazards assumption for each anthropometric variable by creating interaction terms between the participant's age and study period and the measurements. There were no significant violations (all P values >.05). All analyses were 2 sided, and a P value of less than .05 was considered statistically significant. We used SAS software version 9.1 (SAS Institute, Inc, Cary, NC) for the analyses.

      Results

      During 730,446 person-years of follow-up, we identified 801 incident cases of diverticulitis and 383 incident cases of diverticular bleeding. At baseline, 3.7% of men had a BMI <21 kg/m2, 29.8% a BMI between 23 and 25 kg/m2, and 8.1% a BMI of at least 30 kg/m2. The associations between baseline characteristics and BMI, waist circumference, and waist-to-hip ratio were similar (Table 1). Men with elevated BMI, waist circumference, and/or waist-to-hip ratio were on average more likely to be sedentary, to use analgesics, and to consume fat and red meat. Age did not differ across BMI categories, but men with a small waist circumference and/or low waist-to-hip ratio were generally younger than those with larger measurements.
      Table 1Baseline Characteristics According to BMI, Waist Circumference, and Waist-to-Hip Ratio
      BMI (kg/m2)
      6 categories of BMI; <21, 21–22.9, 25–27.4, 27.5–29.9, ≥30.
      Waist circumference (quintiles)
      Q1, <34.25 inches; Q3, 36.25–37.75 inches; Q5, ≥40.25 inches.
      Waist-to-hip ratio (quintiles)
      Q1, <0.89; Q3, 0.93–0.95; Q5, >0.98.
      <2123–25≥30Q1Q3Q5Q1Q3Q5
      No. of individuals172814,0833814618551835902626658495993
      Age (y), mean (SD)54 (10.7)54 (9.9)54 (8.9)51 (9.6)54 (9.7)56 (9.5)51 (9.1)54 (9.6)57 (9.6)
      Smoking, current (%)149.59.48.88.510.17.98.810.6
      NSAID use (%)273237283336303435
      Physical activity, mean (MET, h/wk)292916312317312419
      Daily intake, mean
      calories (kcal/day)203619782014200120092026199820042021
      Alcohol (g/day)101210111212101213
      Fat, total (g/day)
      Total fat and fiber were adjusted for total energy intake (kcal).
      687076687175707273
      Fiber, total (g/day)
      Total fat and fiber were adjusted for total energy intake (kcal).
      222220232120222120
      Red meat (servings/day)3.84.05.03.84.44.94.04.34.7
      NOTE. All variables except age are age standardized.
      NSAID, nonsteroidal anti-inflammatory drug; MET, metabolic equivalent.
      a 6 categories of BMI; <21, 21–22.9, 25–27.4, 27.5–29.9, ≥30.
      b Q1, <34.25 inches; Q3, 36.25–37.75 inches; Q5, ≥40.25 inches.
      c Q1, <0.89; Q3, 0.93–0.95; Q5, >0.98.
      d Total fat and fiber were adjusted for total energy intake (kcal).
      We observed a positive association between BMI and the risk of both incident diverticulitis and diverticular bleeding (Table 2). In the adjusted analysis, men with a BMI ≥30 kg/m2 had a 78% increased risk of diverticulitis when compared with men with a BMI of <21 kg/m2. The effect of BMI was even stronger for diverticular bleeding. Men with a BMI ≥30 kg/m2 were more than 3 times as likely to develop bleeding relative to those with a BMI of <21 kg/m2. In a 10-year period, 14.7 cases of diverticulitis and 8.2 cases of diverticular bleeding would be expected to occur per 1000 obese men (BMI ≥30 kg/m2) compared with 6.6 cases of diverticulitis and 2.6 cases of diverticular bleeding in 1000 lean men (BMI of <21 kg/m2). The multivariable RRs were similar after limiting the analysis of BMI to men who had undergone lower endoscopies (RR, 1.70; 95% CI, 0.89–3.25; P for trend = .02 for diverticulitis; and RR, 2.7; 95% CI, 1.09–7.16; P for trend = .001 for bleeding). The magnitude of the associations between BMI and diverticular outcomes was strengthened when the analyses were limited to men meeting the strictest outcome criteria (multivariable RR, 2.08; 95% CI, 0.81–5.34; P for trend = .07 for diverticulitis [n = 235]; and multivariable RR, 4.87; 95% CI, 0.62–38.4; P for trend = .17 for bleeding [n = 70]). We did not find a significant association between BMI and asymptomatic diverticulosis (n = 1721) in a highest versus lowest category comparison (multivariable RR, 1.16; 95% CI, 0.79–1.69; P for trend = .80).
      Table 2BMI and the RR of Diverticulitis and Diverticular Bleeding
      BMI (kg/m2)P value for trend
      <2121–22.923–24.925–27.427.5–29.9≥30
      Diverticulitis
       Incident cases (n)1883189256138117
       Person-years27,07794,855190,528229,361109,13579,491
       Age-adjusted RR
      Age-adjusted RRs adjusted for age in 1-year intervals and study period in 2-year intervals.
      1.001.301.461.601.762.02<.001
       95% CI0.78–2.170.90–2.370.99–2.591.08–2.891.23–3.33
       Multivariable RR
      Multivariable RRs adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, and current use of nonsteroidal anti-inflammatory drugs and acetaminophen.
      1.001.291.401.481.581.78.004
       95% CI0.77–2.140.86–2.280.92–2.390.97–2.591.08–2.94
      Diverticular bleeding
       Incident cases (n)739841355365
       Person-years27,07794,855190,528229,361109,13579,491
       Age-adjusted RR
      Age-adjusted RRs adjusted for age in 1-year intervals and study period in 2-year intervals.
      1.001.681.832.452.043.46<.001
       95% CI0.75–3.770.84–3.961.15–5.260.92–4.491.58–7.57
       Multivariable RR
      Multivariable RRs adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, and current use of nonsteroidal anti-inflammatory drugs and acetaminophen.
      1.001.681.832.381.913.19<.001
       95% CI0.75–3.760.85–3.971.11–5.090.87–4.231.45–7.00
      a Age-adjusted RRs adjusted for age in 1-year intervals and study period in 2-year intervals.
      b Multivariable RRs adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, and current use of nonsteroidal anti-inflammatory drugs and acetaminophen.
      To assess the relationship between body weight in early adulthood and diverticular complications, we analyzed BMI at age 21 years. BMI at age 21 years was not significantly associated with diverticulitis or diverticular bleeding in the multivariable analyses. The effect of current BMI on the risk of both diverticular outcomes remained unchanged after adjustment for BMI at age 21 years.
      We also explored the relationship between weight gain and incident diverticular complications and again found positive associations. After controlling for weight at age 21 years in addition to other known or potential risk factors, men who gained more than 45 lb since age 21 years had an RR of 1.66 (95% CI, 1.28–2.16; P for trend = .003) for diverticulitis and 2.44 (95% CI, 1.62–3.66; P for trend < .0001) for diverticular bleeding when compared with men who gained less than 5 lb.

       Waist Circumference

      Waist circumference was positively associated with diverticulitis and diverticular bleeding (Table 3). The multivariable RRs for men in the highest quintile of waist circumference compared with the lowest were 1.56 (95% CI, 1.18–2.07; P for trend = .002) for diverticulitis and 1.96 (95% CI, 1.30–2.97; P for trend < .001) for diverticular bleeding. These relationships were essentially unchanged when restricting the analyses to men who had undergone a lower endoscopy (multivariable RR, 1.58; 95% CI, 1.10–2.27; P for trend = .004 for diverticulitis; and multivariable RR, 2.04; 95% CI, 1.14–3.64; P for trend = .003 for bleeding) and were attenuated in men who met the strictest outcome definitions (multivariable RR, 1.40; 95% CI, 0.85–2.31; P for trend = .20 for diverticulitis; and multivariable RR, 1.28; 95% CI, 0.51–3.19; P for trend = .40 for bleeding). Waist circumference was not significantly associated with asymptomatic diverticulosis (multivariable RR, 1.17; 95% CI, 0.96–1.44; P for trend = .42 in a highest vs lowest quintile comparison).
      Table 3Waist Circumference and the RR of Diverticulitis and Diverticular Bleeding
      Waist circumference (quintles)
      Q1, ≤34.25 inches; Q2, 34.5–36 inches; Q3, 36.25–37.75 inches; Q4, 38–40 inches; Q5, ≥40.25 inches.
      P value for trend
      Q1Q2Q3Q4Q5
      Diverticulitis
       Incident cases (n)8611593125137
       Person-years99,564102,19181,158107,47687,986
       Age-adjusted RR
      Age-adjusted RR adjusted for age in 1-year intervals and study period in 2-year intervals.
      1.001.271.291.291.72<.001
       95% CI0.96–1.680.96–1.730.98–1.691.31–2.26
       Multivariable RR
      Multivariable RR adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, current use of nonsteroidal anti-inflammatory drugs and acetaminophen, and height.
      1.001.221.221.201.56.002
       95% CI0.92–1.620.91–1.640.91–1.591.18–2.07
      Diverticular bleeding
       Incident cases (n)3636486275
       Person-years99,564102,19181,158107,47687,986
       Age-adjusted RR
      Age-adjusted RR adjusted for age in 1-year intervals and study period in 2-year intervals.
      1.000.901.451.372.01<.001
       95% CI0.57–1.430.94–2.240.91–2.071.35–3.00
       Multivariable RR
      Multivariable RR adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, current use of nonsteroidal anti-inflammatory drugs and acetaminophen, and height.
      1.000.911.441.361.96<.001
       95% CI0.57–1.440.93–2.230.90–2.081.30–2.97
      a Q1, ≤34.25 inches; Q2, 34.5–36 inches; Q3, 36.25–37.75 inches; Q4, 38–40 inches; Q5, ≥40.25 inches.
      b Age-adjusted RR adjusted for age in 1-year intervals and study period in 2-year intervals.
      c Multivariable RR adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, current use of nonsteroidal anti-inflammatory drugs and acetaminophen, and height.

       Waist-to-Hip Ratio

      Waist-to-hip ratio was similarly associated with an increased risk of incident diverticular complications (Table 4). The multivariable RRs for men in the highest quintile of waist-to-hip ratio compared with those in the lowest were 1.62 (95% CI, 1.23–2.14; P for trend = .001) for diverticulitis and 1.91 (95% CI, 1.26–2.90; P for trend = .001) for diverticular bleeding. The associations between waist-to-hip ratio and diverticular outcomes remained largely unchanged after adjusting for BMI (multivariable RR, 1.50; 95% CI, 1.13–2.00; P for trend = .003 for diverticulitis; and multivariable RR, 1.66; 95% CI, 1.08–2.54; P for trend = .004 for diverticular bleeding). However, the relationship with BMI was attenuated when adjusted for waist-to-hip ratio (multivariable RR, 1.61; 95% CI, 0.97–2.67; P for trend = .22 for diverticulitis; and multivariable RR, 2.73; 95% CI, 1.24–6.05; P for trend = .09 for bleeding). Restricting the analysis to men who had undergone lower endoscopy or who met the strictest definitions of outcome had little impact on the associations between waist-to-hip ratio and diverticular outcomes; multivariable RRs for diverticulitis were 1.48 (95% CI, 1.04–2.12; P for trend = .02) and 1.87 (95% CI, 1.12–3.09; P for trend = .01), respectively, and for diverticular bleeding were 1.90 (95% CI, 1.09–3.33; P for trend = .01) and 2.53 (95% CI, 0.83–7.78; P for trend = .05), respectively. In a highest to lowest quintile comparison, waist-to-hip ratio was not associated with asymptomatic diverticulosis (multivariable RR, 1.05; 95% CI, 0.84–1.31; P for trend = .66).
      Table 4Waist-to-Hip Ratio and the RR of Diverticulitis and Diverticular Bleeding
      Waist-to-hip ratio (quintiles)
      Q1, <0.89; Q2, 0.89–0.92; Q3, 0.93–0.95; Q4, 0.96–0.98; Q5, >0.98.
      P value for trend
      12345
      Diverticulitis
       Incident cases (n)84109107121135
       Person-years101,529103,13591,46892,24188,660
       Age-adjusted RR
      Age-adjusted RR adjusted for age in 1-year intervals and study period in 2-year intervals.
      1.001.261.391.541.81<.001
       95% CI0.95–1.681.04–1.851.16–2.041.37–2.38
       Multivariable RR
      Multivariable RR adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, and current use of nonsteroidal anti-inflammatory drugs and acetaminophen.
      1.001.221.301.411.62<.001
       95% CI0.92–1.630.97–1.731.06–1.871.23–2.14
      Diverticular bleeding
       Incident cases (n)3340505677
       Person-years101,529103,13591,46892,24188,660
       Age-adjusted RR
      Age-adjusted RR adjusted for age in 1-year intervals and study period in 2-year intervals.
      1.001.081.471.572.20<.001
       95% CI0.68–1.710.94–2.281.01–2.411.45–3.32
       Multivariable RR
      Multivariable RR adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, and current use of nonsteroidal anti-inflammatory drugs and acetaminophen.
      1.001.051.371.431.91<.001
       95% CI0.66–1.670.88–2.130.92–2.201.26–2.90
      a Q1, <0.89; Q2, 0.89–0.92; Q3, 0.93–0.95; Q4, 0.96–0.98; Q5, >0.98.
      b Age-adjusted RR adjusted for age in 1-year intervals and study period in 2-year intervals.
      c Multivariable RR adjusted for age in 1-year intervals, study period in 2-year intervals, dietary intake of calories, fat, fiber, and red meat, physical activity, and current use of nonsteroidal anti-inflammatory drugs and acetaminophen.

      Discussion

      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 relationship 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.
      • Konvolinka C.W.
      Acute diverticulitis under age forty.
      • Mader T.J.
      Acute diverticulitis in young adults.
      • Schauer P.R.
      • Ramos R.
      • Ghiatas A.A.
      • et al.
      Virulent diverticular disease in young obese men.
      • Schweitzer J.
      • Casillas R.A.
      • Collins J.C.
      Acute diverticulitis in the young adult is not “virulent”.
      • Zaidi E.
      • Daly B.
      CT and clinical features of acute diverticulitis in an urban U.S. population: rising frequency in young, obese adults.
      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.
      • Konvolinka C.W.
      Acute diverticulitis under age forty.
      • Schauer P.R.
      • Ramos R.
      • Ghiatas A.A.
      • et al.
      Virulent diverticular disease in young obese men.
      • Zaidi E.
      • Daly B.
      CT and clinical features of acute diverticulitis in an urban U.S. population: rising frequency in young, obese adults.
      In a case-control study, comparisons were made between 18 unmatched controls with uncomplicated diverticulosis and 43 patients with diverticulitis.
      • Dobbins C.
      • Defontgalland D.
      • Duthie G.
      • et al.
      The relationship of obesity to the complications of diverticular disease.
      BMI was significantly higher in patients with recurrent diverticulitis or perforated diverticulitis compared with 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).
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Prospective study of physical activity and the risk of symptomatic diverticular disease in men.
      In a study of 112 cases from a prospective cardiovascular prevention trial in Sweden, BMI was significantly associated with symptomatic diverticular disease in men.
      • Rosemar A.
      • Angeras U.
      • Rosengren A.
      Body mass index and diverticular disease: a 28-year follow-up study in men.
      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 nonsteroidal anti-inflammatory drugs, which are putative risk factors for diverticular complications
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Prospective study of physical activity and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      A prospective study of diet and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rimm E.B.
      • et al.
      Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men.
      • Aldoori W.H.
      • Giovannucci E.L.
      • Rockett H.R.
      • et al.
      A prospective study of dietary fiber types and symptomatic diverticular disease in men.
      • Laine L.
      • Smith R.
      • Min K.
      • et al.
      Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs.
      • Manousos O.
      • Day N.E.
      • Tzonou A.
      • et al.
      Diet and other factors in the aetiology of diverticulosis: an epidemiological study in Greece.
      • Morris C.R.
      • Harvey I.M.
      • Stebbings W.S.
      • et al.
      Anti-inflammatory drugs, analgesics and the risk of perforated colonic diverticular disease.
      and are also associated with obesity.
      Counterweight Project Team
      The impact of obesity on drug prescribing in primary care.
      • Davis J.N.
      • Hodges V.A.
      • Gillham M.B.
      Normal-weight adults consume more fiber and fruit than their age- and height-matched overweight/obese counterparts.
      • Duvigneaud N.
      • Wijndaele K.
      • Matton L.
      • et al.
      Dietary factors associated with obesity indicators and level of sports participation in Flemish adults: a cross-sectional study.
      Second, prior studies had limited sample sizes. In comparison with the prior Health Professionals Follow-up Study, the current study uses 12 additional years of follow-up. The large number of cases in the current study enabled us to evaluate diverticulitis, diverticular bleeding, and diverticulosis without these complications as separate end points. This is important because diverticular bleeding and diverticulitis are distinct entities that likely evolve through different biologic pathways.
      • Meyers M.A.
      • Alonso D.R.
      • Gray G.F.
      • et al.
      Pathogenesis of bleeding colonic diverticulosis.
      Nonspecific bowel symptoms are difficult to ascribe to diverticulosis and may be more common in obese individuals in general.
      • Delgado-Aros S.
      • Locke III, G.R.
      • Camilleri M.
      • et al.
      Obesity is associated with increased risk of gastrointestinal symptoms: a population-based study.
      • Levy R.L.
      • Linde J.A.
      • Feld K.A.
      • et al.
      The association of gastrointestinal symptoms with weight, diet, and exercise in weight-loss program participants.
      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.
      • El-Serag H.B.
      Obesity and disease of the esophagus and colon.
      • Corley D.A.
      • Kubo A.
      • Levin T.R.
      • et al.
      Abdominal obesity and body mass index as risk factors for Barrett's esophagus.
      • Giovannucci E.
      • Michaud D.
      The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas.
      • Pischon T.
      • Lahmann P.H.
      • Boeing H.
      • et al.
      Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC).
      Finally, previous studies (except the Health Professionals Follow-up Study) have included only hospitalized patients and may not be generalizable to the larger group of patients managed in the outpatient setting.
      • Schechter S.
      • Mulvey J.
      • Eisenstat T.E.
      Management of uncomplicated acute diverticulitis: results of a survey.
      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 believed to contribute to diverticular complications.
      • Morris C.R.
      • Harvey I.M.
      • Stebbings W.S.
      • et al.
      Epidemiology of perforated colonic diverticular disease.
      Adipose tissue secretes a number of cytokines known to participate in local and generalized inflammation.
      • Shoelson S.E.
      • Herrero L.
      • Naaz A.
      Obesity, inflammation, and insulin resistance.
      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.
      • Ley R.E.
      • Turnbaugh P.J.
      • Klein S.
      • et al.
      Microbial ecology: human gut microbes associated with obesity.
      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.
      • Korzenik J.R.
      Case closed? Diverticulitis: epidemiology and fiber.
      • Floch M.H.
      • White J.A.
      Management of diverticular disease is changing.
      Obesity may influence diverticular bleeding through pathways that affect vascular integrity.
      • Meyers M.A.
      • Alonso D.R.
      • Gray G.F.
      • et al.
      Pathogenesis of bleeding colonic diverticulosis.
      Lastly, obesity may contribute to the development of diverticulosis. Obesity was not associated with asymptomatic diverticulosis in our study or in previous reports.
      • Horner J.L.
      Natural history of diverticulosis of the colon.
      • Hughes L.E.
      Postmortem survey of diverticular disease of the colon II. The muscular abnormality of the sigmoid colon.
      However, the CIs in our analysis were relatively wide and random misclassification due to imperfect recall of endoscopy results could have biased the results toward 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.
      • Pi-Sunyer F.X.
      The obesity epidemic: pathophysiology and consequences of obesity.
      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, because 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 end point 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 end points [Supplementary Table 1; see supplemental material online at www.gastrojournal.org]) 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 older than 40 years. Nonetheless, diverticulosis is rare in young individuals, and men and women appear to be affected equally.
      • Hughes L.E.
      Postmortem survey of diverticular disease of the colon II. The muscular abnormality of the sigmoid colon.
      • Stollman N.H.
      • Raskin J.B.
      Diagnosis and management of diverticular disease of the colon in adults Ad Hoc Practice Parameters Committee of the American College of Gastroenterology.
      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
      • Kang J.Y.
      • Hoare J.
      • Tinto A.
      • et al.
      Diverticular disease of the colon—on the rise: a study of hospital admissions in England between 1989/1990 and 1999/2000.
      • Ogden C.L.
      • Carroll M.D.
      • Curtin L.R.
      • et al.
      Prevalence of overweight and obesity in the United States, 1999–2004.
      and the considerable risk of recurrent complications.
      • Anaya D.A.
      • Flum D.R.
      Risk of emergency colectomy and colostomy in patients with diverticular disease.
      • Longstreth G.F.
      Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study.
      Indeed, with few known modifiable risk factors, current preventative measures rely heavily on prophylactic colectomy.
      • Stollman N.H.
      • Raskin J.B.
      Diagnosis and management of diverticular disease of the colon in adults Ad Hoc Practice Parameters Committee of the American College of Gastroenterology.
      The link between obesity and diverticular disease may also direct future studies aimed at uncovering mechanisms of disease.

      Supplementary data

      Supplementary Table 1RRs of Variables Potentially Associated With Diverticulitis and Diverticular Bleeding
      VariableDiverticulitisDiverticular bleeding
      BMI (kg/m2)
       <211 (reference)1 (reference)
       21–22.91.29 (077–2.14)1.68 (0.75–3.76)
       23–24.91.40 (0.86–2.28)1.83 (0.85–3.97)
       25–27.41.48 (0.92–2.39)2.38 (1.11–5.09)
       27.5–29.91.58 (0.97–2.59)1.91 (0.87–4.23)
       ≥301.78 (1.08–2.94)3.19 (1.45–7.00)
      Total fat intake (quintiles)
       Q11 (reference)1 (reference)
       Q21.00 (0.78–1.29)0.88 (0.64–1.21)
       Q31.25 (0.98–1.60)1.00 (0.73–1.38)
       Q41.20 (0.93–1.55)0.68 (0.48–0.98)
       Q51.14 (0.88–1.48)0.67 (0.47–0.97)
      Total fiber intake (quintiles)
       Q11 (reference)1 (reference)
       Q20.91 (0.74–1.11)1.04 (0.78–1.40)
       Q30.83 (0.67–1.03)0.64 (0.46–0.90)
       Q40.83 (0.66–1.03)0.73 (0.52–1.01)
       Q50.64 (0.49–0.83)0.61 (0.42–0.87)
      Red meat intake (quintiles)
       Q11 (reference)1 (reference)
       Q21.37 (1.02–1.84)1.18 (0.81–1.71)
       Q31.48 (1.17–1.89)0.95 (0.68–1.32)
       Q41.40 (1.08–1.81)0.88 (0.62–1.27)
       Q51.40 (1.08–1.81)0.99 (0.70–1.42)
      Total energy intake (kcal)
       Q11 (reference)1 (reference)
       Q21.09 (0.88–1.35)1.45 (1.07–1.97)
       Q30.96 (0.77–1.21)1.03 (0.73–1.45)
       Q40.93 (0.74–1.17)0.84 (0.58–1.21)
       Q50.90 (0.70–1.14)1.42 (1.01–1.98)
      Physical activity (MET, h/wk)
       ≤8.21 (reference)1 (reference)
       8.3–19.00.89 (0.73–1.08)0.85 (0.65–1.12)
       19.1–33.50.79 (0.65–0.97)0.70 (0.52–0.94)
       33.6–57.30.80 (0.63–1.00)0.61 (0.43–0.87)
       ≥57.40.85 (0.65–1.12)0.71 (0.48–1.06)
      NSAID use
       No1 (reference)1 (reference)
       Yes1.31 (1.13–1.53)1.69 (1.35–2.12)
      Acetaminophen use
       No1 (reference)1 (reference)
       Yes1.20 (0.92–1.55)1.35 (0.95–1.92)
      NOTE. All values are expressed as RR (95% CI).
      MET, metabolic equivalent; NSAID, nonsteroidal anti-inflammatory drug.

      References

        • Sandler R.S.
        • Everhart J.E.
        • Donowitz M.
        • et al.
        The burden of selected digestive diseases in the United States.
        Gastroenterology. 2002; 122: 1500-1511
        • Shaheen N.J.
        • Hansen R.A.
        • Morgan D.R.
        • et al.
        The burden of gastrointestinal and liver diseases, 2006.
        Am J Gastroenterol. 2006; 101: 2128-2138
        • Welch C.E.
        • Allen A.W.
        • Donaldson G.A.
        An appraisal of resection of the colon for diverticulitis of the sigmoid.
        Ann Surg. 1953; 138: 332-343
        • Horner J.L.
        Natural history of diverticulosis of the colon.
        Am J Dig Dis. 1958; 3: 343-350
        • Painter N.S.
        Diverticular disease of the colon—a disease of the century.
        Lancet. 1969; 2: 586-588
      1. Overweight, obesity, and health risk.
        Arch Intern Med. 2000; 160: 898-904
        • El-Serag H.B.
        Obesity and disease of the esophagus and colon.
        Gastroenterol Clin North Am. 2005; 34: 63-82
        • Ioannou G.N.
        • Weiss N.S.
        • Kowdley K.V.
        • et al.
        Is obesity a risk factor for cirrhosis-related death or hospitalization?.
        Gastroenterology. 2003; 125: 1053-1059
        • Michaud D.S.
        • Giovannucci E.
        • Willett W.C.
        • et al.
        Physical activity, obesity, height, and the risk of pancreatic cancer.
        JAMA. 2001; 286: 921-929
        • Shoelson S.E.
        • Herrero L.
        • Naaz A.
        Obesity, inflammation, and insulin resistance.
        Gastroenterology. 2007; 132: 2169-2180
        • Korzenik J.R.
        Case closed?.
        J Clin Gastroenterol. 2006; 40: S112-S116
        • Ley R.E.
        • Turnbaugh P.J.
        • Klein S.
        • et al.
        Microbial ecology: human gut microbes associated with obesity.
        Nature. 2006; 444: 1022-1023
        • Dobbins C.
        • Defontgalland D.
        • Duthie G.
        • et al.
        The relationship of obesity to the complications of diverticular disease.
        Colorectal Dis. 2006; 8: 37-40
        • Konvolinka C.W.
        Acute diverticulitis under age forty.
        Am J Surg. 1994; 167: 562-565
        • Mader T.J.
        Acute diverticulitis in young adults.
        J Emerg Med. 1994; 12: 779-782
        • Schauer P.R.
        • Ramos R.
        • Ghiatas A.A.
        • et al.
        Virulent diverticular disease in young obese men.
        Am J Surg. 1992; 164 (discussion 446–448): 443-446
        • Schweitzer J.
        • Casillas R.A.
        • Collins J.C.
        Acute diverticulitis in the young adult is not “virulent”.
        Am Surg. 2002; 68: 1044-1047
        • Zaidi E.
        • Daly B.
        CT and clinical features of acute diverticulitis in an urban U.S. population: rising frequency in young, obese adults.
        AJR Am J Roentgenol. 2006; 187: 689-694
        • Aldoori W.H.
        • Giovannucci E.L.
        • Rimm E.B.
        • et al.
        Prospective study of physical activity and the risk of symptomatic diverticular disease in men.
        Gut. 1995; 36: 276-282
        • Rosemar A.
        • Angeras U.
        • Rosengren A.
        Body mass index and diverticular disease: a 28-year follow-up study in men.
        Dis Colon Rectum. 2008; 51: 450-455
        • Meyers M.A.
        • Alonso D.R.
        • Gray G.F.
        • et al.
        Pathogenesis of bleeding colonic diverticulosis.
        Gastroenterology. 1976; 71: 577-583
        • Corley D.A.
        • Kubo A.
        • Levin T.R.
        • et al.
        Abdominal obesity and body mass index as risk factors for Barrett's esophagus.
        Gastroenterology. 2007; 133 (quiz 311): 34-41
        • Giovannucci E.
        • Michaud D.
        The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas.
        Gastroenterology. 2007; 132: 2208-2225
        • Rimm E.B.
        • Stampfer M.J.
        • Colditz G.A.
        • et al.
        Validity of self-reported waist and hip circumferences in men and women.
        Epidemiology. 1990; 1: 466-473
        • Aldoori W.H.
        • Giovannucci E.L.
        • Rimm E.B.
        • et al.
        A prospective study of diet and the risk of symptomatic diverticular disease in men.
        Am J Clin Nutr. 1994; 60: 757-764
        • Aldoori W.H.
        • Giovannucci E.L.
        • Rimm E.B.
        • et al.
        Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men.
        Arch Fam Med. 1998; 7: 255-260
        • Aldoori W.H.
        • Giovannucci E.L.
        • Rockett H.R.
        • et al.
        A prospective study of dietary fiber types and symptomatic diverticular disease in men.
        J Nutr. 1998; 128: 714-719
        • Laine L.
        • Smith R.
        • Min K.
        • et al.
        Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs.
        Aliment Pharmacol Ther. 2006; 24: 751-767
        • Manousos O.
        • Day N.E.
        • Tzonou A.
        • et al.
        Diet and other factors in the aetiology of diverticulosis: an epidemiological study in Greece.
        Gut. 1985; 26: 544-549
        • Morris C.R.
        • Harvey I.M.
        • Stebbings W.S.
        • et al.
        Anti-inflammatory drugs, analgesics and the risk of perforated colonic diverticular disease.
        Br J Surg. 2003; 90: 1267-1272
        • Chasan-Taber S.
        • Rimm E.B.
        • Stampfer M.J.
        • et al.
        Reproducibility and validity of a self-administered physical activity questionnaire for male health professionals.
        Epidemiology. 1996; 7: 81-86
        • Rimm E.B.
        • Giovannucci E.L.
        • Stampfer M.J.
        • et al.
        Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals.
        Am J Epidemiol. 1992; 135 (discussion 1127–1136): 1114-1126
      2. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report.
        Obes Res. 1998; 6: 51S-209S
        • Cox D.R.
        Regression models and life tables.
        J R Stat Soc B. 1972; 34: 187-220
        • Counterweight Project Team
        The impact of obesity on drug prescribing in primary care.
        Br J Gen Pract. 2005; 55: 743-749
        • Davis J.N.
        • Hodges V.A.
        • Gillham M.B.
        Normal-weight adults consume more fiber and fruit than their age- and height-matched overweight/obese counterparts.
        J Am Diet Assoc. 2006; 106: 833-840
        • Duvigneaud N.
        • Wijndaele K.
        • Matton L.
        • et al.
        Dietary factors associated with obesity indicators and level of sports participation in Flemish adults: a cross-sectional study.
        Nutr J. 2007; 6: 26
        • Delgado-Aros S.
        • Locke III, G.R.
        • Camilleri M.
        • et al.
        Obesity is associated with increased risk of gastrointestinal symptoms: a population-based study.
        Am J Gastroenterol. 2004; 99: 1801-1806
        • Levy R.L.
        • Linde J.A.
        • Feld K.A.
        • et al.
        The association of gastrointestinal symptoms with weight, diet, and exercise in weight-loss program participants.
        Clin Gastroenterol Hepatol. 2005; 3: 992-996
        • Pischon T.
        • Lahmann P.H.
        • Boeing H.
        • et al.
        Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC).
        J Natl Cancer Inst. 2006; 98: 920-931
        • Schechter S.
        • Mulvey J.
        • Eisenstat T.E.
        Management of uncomplicated acute diverticulitis: results of a survey.
        Dis Colon Rectum. 1999; 42 (discussion 475–476): 470-475
        • Morris C.R.
        • Harvey I.M.
        • Stebbings W.S.
        • et al.
        Epidemiology of perforated colonic diverticular disease.
        Postgrad Med J. 2002; 78: 654-658
        • Floch M.H.
        • White J.A.
        Management of diverticular disease is changing.
        World J Gastroenterol. 2006; 12: 3225-3228
        • Hughes L.E.
        Postmortem survey of diverticular disease of the colon.
        Gut. 1969; 10: 344-351
        • Pi-Sunyer F.X.
        The obesity epidemic: pathophysiology and consequences of obesity.
        Obes Res. 2002; 10: 97S-104S
        • Stollman N.H.
        • Raskin J.B.
        Diagnosis and management of diverticular disease of the colon in adults.
        Am J Gastroenterol. 1999; 94: 3110-3121
        • Kang J.Y.
        • Hoare J.
        • Tinto A.
        • et al.
        Diverticular disease of the colon—on the rise: a study of hospital admissions in England between 1989/1990 and 1999/2000.
        Aliment Pharmacol Ther. 2003; 17: 1189-1195
        • Ogden C.L.
        • Carroll M.D.
        • Curtin L.R.
        • et al.
        Prevalence of overweight and obesity in the United States, 1999–2004.
        JAMA. 2006; 295: 1549-1555
        • Anaya D.A.
        • Flum D.R.
        Risk of emergency colectomy and colostomy in patients with diverticular disease.
        Arch Surg. 2005; 140: 681-685
        • Longstreth G.F.
        Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study.
        Am J Gastroenterol. 1997; 92: 419-424