Trend and Risk Factors of Diverticulosis in Japan - Semantic Scholar

RESEARCH ARTICLE

Trend and Risk Factors of Diverticulosis in Japan: Age, Gender, and Lifestyle/MetabolicRelated Factors May Cooperatively Affect on the Colorectal Diverticula Formation Nobutake Yamamichi1*, Takeshi Shimamoto1,2, Yu Takahashi1, Yoshiki Sakaguchi1, Hikaru Kakimoto1, Rie Matsuda1, Yosuke Kataoka1, Itaru Saito1, Yosuke Tsuji1, Seiichi Yakabi1, Chihiro Takeuchi1, Chihiro Minatsuki1, Keiko Niimi1, Itsuko AsadaHirayama1, Chiemi Nakayama1, Satoshi Ono1, Shinya Kodashima1, Daisuke Yamaguchi1, Mitsuhiro Fujishiro1, Yutaka Yamaji1, Ryoichi Wada2, Toru Mitsushima2, Kazuhiko Koike1 1 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan, 2 Kameda Medical Center Makuhari, CD-2, 1–3, Nakase, Mihama-ku, Chiba-city, Japan * [email protected] OPEN ACCESS Citation: Yamamichi N, Shimamoto T, Takahashi Y, Sakaguchi Y, Kakimoto H, Matsuda R, et al. (2015) Trend and Risk Factors of Diverticulosis in Japan: Age, Gender, and Lifestyle/Metabolic-Related Factors May Cooperatively Affect on the Colorectal Diverticula Formation. PLoS ONE 10(4): e0123688. doi:10.1371/journal.pone.0123688 Academic Editor: John Green, University Hospital Llandough, UNITED KINGDOM Received: October 21, 2014 Accepted: February 23, 2015 Published: April 10, 2015 Copyright: © 2015 Yamamichi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All data are within the paper. Funding: This work was partly supported by Grantin-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (Grant number: 25460381), and also partly supported by a grant from the Smoking Research Foundation of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Abstract Background Despite the marked increase of diverticulosis, its risk factors have not been adequately elucidated. We therefore aim to identify significantly associated factors with diverticulosis. We also aim to investigate the present state of diverticulosis in Japan.

Methods We reviewed the medical records from 1990 to 2010 that included the data of consecutive 62,503 asymptomatic colonoscopy examinees from the general population in Japan. Most recent 3,327 examinees were analyzed with 16 background factors.

Results Among the 62,503 subjects (47,325 men and 15,178 women; 52.1 ± 9.2 years old), diverticulosis was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0% (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than the former in all age groups and for both genders. Considering the anatomical locations of colorectal diverticula, left-sided ones have markedly increased with age but not significantly changed with times. Univariate analyses of the 3,327 subjects showed significant association of diverticulosis with four basic factors (age, sex, body mass index, blood pressure), three life style-related factor (smoking, drinking, severe weight increase in adulthood), and two blood test values (triglyceride, HbA1c). The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that age (β = 0.217-0.674, OR = 1.24-1.96), male gender (β = 0.185,

PLOS ONE | DOI:10.1371/journal.pone.0123688 April 10, 2015

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Trend and Risk Factors of Diverticulosis in Japan

Competing Interests: The authors have declared that no competing interests exist.

OR = 1.20), smoking (β = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (β = 0.153, OR = 1.17), HbA1c (β = 0.136, OR = 1.15), drinking (β = 0.109, OR = 1.11), and serum triglyceride (β = 0.098, OR = 1.10) showed significantly positive association with diverticulosis whereas body mass index and blood pressure did not.

Conclusions The large-scale data of asymptomatic colonoscopy examinees from the general population from 1990 to 2010 indicated that the prevalence of diverticulosis is still increasing in Japan. Age, male gender, smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum triglyceride showed significant positive association with diverticulosis.

Introduction The exact prevalence of diverticulosis is difficult to define, because most subjects with diverticulosis might be asymptomatic and also because the large intestine of healthy individuals is not usually examined [1]. Nevertheless, it is broadly accepted that rates of diverticulosis have obviously increased over times worldwide [1–5]. In Japan, several early studies reported the prevalence of diverticulosis based on the barium enema examination: 1.6% in 1975 [6], 7.8% in 1983 [7], 13.3% in 1987 [8], 15.7% in 1995 [9], and 23.6% in 2000 [10]. These reports indicated that prevalence of Japan had increased like Western countries [2, 3]. However, recent reports evaluating the prevalence of diverticulosis among the asymptomatic subjects from the general population are few: thence, one of the aims of this study is investigating the present state of diverticulosis in Japan, one of the typical developing countries in East Asia. Despite the marked increase of disease rate in the last several decades [1], pathogenesis and risk factors of diverticulosis have not been adequately elucidated [4]. For the basic factors, advancing age is the definite risk factor of diverticulosis validated by many previous studies [6, 7, 9, 11–13]. On the contrary, an association of gender with diverticulosis is still controversial [6, 14, 15]. Low-fiber diet has been repeatedly reported as the risk factor of diverticulosis [11, 16– 18], but a recent study achieved the opposite result [13]. As for drinking, results of some reports considered alcohol as a risk factor of diverticulosis whereas other reports did not [19–22]. Association of smoking with diverticulosis is also controversial [13, 21–23]. Recently, several studies indicated that body mass index and/or obesity may be associated with diverticulosis [24–26]. As a whole, definitively associated factors for diverticulosis have not been identified except for advancing age. Therefore, the main purpose of this study is to evaluate associations of several background factors with diverticulosis.

Methods Asymptomatic colonoscopy examinees from the general Japanese population for 21 years Of the total 313,729 asymptomatic general adults who visited our medical institute (Kameda Medical Center Makuhari, Chiba, Japan) from 1990 to 2010, we retrospectively reviewed the medical records of consecutive 62,503 subjects (47,325 men and 15,178 women) who underwent total colonoscopy as part of the medical checkup (Fig 1A).


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Fig 1. Two flow charts for the present study. (A) Flowchart to select the general asymptomatic colonoscopy examinees for an epidemiologic survey of 21 years in Japan. (B) Flowchart for the selection of study subjects to evaluate univariate and multivariate association between diverticulosis and several background factors. doi:10.1371/journal.pone.0123688.g001

Study subjects to evaluate the associated background factors of diverticulosis Of the 20,773 subjects who received medical checkup at our medical institute and approved participating in our study, 5,021 subjects underwent colonoscopy from 2008 to 2012 (Fig 1B). This study was approved by the ethics committee of the University of Tokyo, and written informed consents were obtained from all the study participants according to the Declaration of Helsinki.

Total colonoscopy and diagnosis of diverticulosis For bowel preparation for colonoscopy, each subject ingested 2 liters of polyethylene glycol electrolyte (PEG) solution. In case of inadequate preparation, the examinee additionally ingested 0.5–1 litters of PEG solution. After confirming that the bowel's output runs clear, total colonoscopy was performed by well-trained endoscopists both in the morning and afternoon. In case of failure to reach the cecum, the subject was omitted in the present analysis. During the procedure of total colonoscopy, the locations of diverticula were documented. The anatomical locations of colorectal diverticula were classified into cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum.

Categorization of blood pressure According to the guideline of the Japanese society of hypertension [27], total subjects were classified into three classes as follows; i) optimal blood pressure: systolic blood pressure (SBP) lower than 120 mmHg and diastolic blood pressure (DBP) lower than 80 mmHg, ii) hypertension: SBP equal or more than 140 mmHg or DBP equal or more than 90 mmHg, and iii) normal range blood pressure: a combination of SBP and DBP not fallen under optimal blood pressure and hypertension.

Evaluation of serum anti-Helicobacter pylori IgG, Alcohol Drinking, and Smoking Serum anti-Helicobacter pylori IgG was measured using a commercial kit (E-plate “EIKEN” Helicobacter pylori antibody, Eiken Chemical Co LTD., Tokyo, Japan) as we previously reported [28–30]. According to the manufacture’s instruction, the titer of anti-Helicobacter pylori IgG 10 U/ml was considered as Helicobacter pylori-positive. For alcohol drinking, the study subjects were scored based on the 5-grade scale: never (0/ month), seldom (1-2/month), sometimes (1-2/week), often (3-5/week), and always (6-7/week, almost every day) [28, 30]. These further classified into “rarely drinking” (never or seldom) or “usually drinking” (sometimes, often, or always) [28, 29, 31]. For smoking, the subjects were classified into three groups: “current smoker”, “past habitual smoker”, and “lifelong nonsmoker” [30]. Based on our previous study [32, 33], we used additional four questions to assess the lifestylerelated factors: 1) Has your body weight markedly increased in adulthood (more than 10 kg from age 20 years)? 2) Do you have a feeling of inadequate sleep? 3) Do you have a habit of


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frequent skipping of breakfast (more than three times a week)? 4) Do you have a habit of having dinner within two hours before going to bed?

Statistical Analyses We used JMP 10 software or SAS 9.1.3 (SAS Institute Inc. Cray, NC, USA) for statistical analyses. In the univariate analyses, categorical data were analyzed by Pearson’s chi-square test, and continuous data were analyzed by Welch’s t-test. Covariates associated with the presence of diverticulosis were carefully selected based on known confounders and clinical knowledge as follows: age (categorical data), sex (categorical data), body mass index (categorical data), blood pressure (categorical data), habit of smoking (categorical data), habit of drinking (categorical data), severe weight increase in adulthood (categorical data), feeling of inadequate sleep (categorical data), habit of frequent skipping of breakfast (categorical data), habit of having dinner within two hours before going to bed (categorical data), anti-Helicobacter pylori IgG (categorical data), serum T-chol (total cholesterol, continuous data, [mg/dl]), serum LDL-chol (lowdensity lipoprotein cholesterol, continuous data, [mg/dl]), serum triglyceride (continuous data, [mg/dl]), serum albumin (continuous data, [g/dl]), and serum HbA1c (glycated hemoglobin, continuous data, [%]). To compare the incidence trend of anatomical locations of colorectal diverticula in 1990– 2000 and that in 2001–2010, we constructed the interaction terms of diverticula’s locations with advancing age or an examination period to apply “Zero-Inflated Poisson model” [34]. To evaluate relative strengths of predictors on diverticulosis, they were calculated by fitting a logistic regression model using all the relevant variables, which were derived from the univarite analyses. In all the analyses, p values