DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH ARTICLE Diabetes Metab Res Rev 2016; 32: 95–101. Published online 15 August 2015 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/dmrr.2677
Helicobacter pylori infection is associated with type 2 diabetes among a middle- and old-age Chinese population
Xu Han1, Yaru Li1, Jing Wang1, Bing Liu1, Hua Hu1, Xiulou Li2, Kun Yang2, Jing Yuan1, Ping Yao1, Sheng Wei1, Youjie Wang1, Yuan Liang1, Xiaoping Miao1, Xiaomin Zhang1, Huan Guo1, Handong Yang2, Tangchun Wu1, Meian He1* 1
Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China
2
Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China *Correspondence to: Meian He, Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, Hubei, 430030, China. E-mail: [email protected]
Abstract Background Although the association of Helicobacter pylori (H. pylori) infection with diabetes mellitus has been evaluated, findings are controversial. This study investigated the association in a Chinese population. Methods A cross-sectional study, including a total of 30 810 subjects from the Dongfeng-Tongji Cohort study, was conducted. H. pylori status was measured via 14 C urea breath test. Association analysis was performed by logistic regression, with multivariable adjustment for sex, age, body mass index, smoking, alcohol consumption, family history of diabetes, physical activity and the use of antibiotics. Results Among a middle-age and old-age Chinese population, individuals with H. pylori infection also had a higher prevalence of type 2 diabetes (21.3% versus 20.2%, p = 0.026). H. pylori infection was associated with higher risk of type 2 diabetes [odds ratio, 1.08 (95% confidence interval: 1.02–1.14); p = 0.008] after adjustment for other confounders. The association was significant among women, those who were above 65 years old, not overweight or obese, and those who did not smoke, did not consume alcohol and without family history of diabetes. However, there was no interaction between H. pylori infection and other traditional risk factors on type 2 diabetes risk. Subjects with H. pylori infection had a lower level of high-density lipoprotein cholesterol (p < 0.0001) and higher levels of blood pressure (p < 0.001), total cholesterol, HbA1c and fasting blood glucose (p < 0.0001) than those who did not. Conclusions These findings suggested that H. pylori infection was associated with the risk of type 2 diabetes in a middle-age and old-age Chinese population. Copyright © 2015 John Wiley & Sons, Ltd. Keywords
Helicobacter pylori; type 2 diabetes; interaction
Introduction Received: 26 March 2015 Revised: 11 June 2015 Accepted: 1 July 2015
Copyright © 2015 John Wiley & Sons, Ltd.
The prevalence of diabetes mellitus has increased dramatically throughout the world, and the overall prevalence of diabetes was estimated to be 11.6% in the Chinese adult population [1]. Diabetes mellitus is a multifactorial disorder resulting from genetic, environmental, lifestyle and social factors. Environmental factors account for a high proportion in the complex pathogenesis of
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diabetes mellitus [2]. Chronic infection constitutes one of the major environmental etiologic factors, and the effects of infectious agents have been studied. Helicobacter pylori (H. pylori) are gram-negative bacteria that colonize the human stomach, causing chronic gastritis, gastric malignancy and peptic ulcer disease, and have been recognized as a major public health concern all over the world [3]. The prevalence of H. pylori infection ranges from 41.35–72.3% and may fluctuate among the different population and different geographic areas [4]. H. pylori may have an influence on cardiovascular diseases and metabolic syndrome through the elevations in inflammatory cytokines levels such as C-reactive protein (CRP) and interleukin-6, which were also implicated in the pathogenesis of diabetes mellitus [5–7]. Previous studies have suggested H. pylori to be positively associated with diabetes mellitus [2,8,9]. However, other studies found no association between them [10,11]. Therefore, the relationship between H. pylori infection and the risk of diabetes mellitus still remains to be clearly defined. In this cross-sectional study including 30 810 participants from the Dongfeng-Tongji Cohort study, we assessed the association between H. pylori infection and the risk of type 2 diabetes as well as its traditional risk factors.
Materials and methods Study population The Dongfeng-Tongji Cohort study was launched in 2008 among retirees of Dongfeng Motor Corporation (DMC) in Shiyan City, Hubei province [12]. DMC was founded in 1969 and is one of the three largest auto manufacturers in China. After follow-up for the first time in 2013, we recruited a total of 38 295 retirees, and 34 708 retirees took physical examination and provided questionnaires. Data allowing the determination of both H. pylori and diabetes mellitus status were available for 30 810 of the participants after excluding those with missing data. The sociodemographic characteristics were similar between participants included in the present study and those excluded. The study has been approved by the Medical Ethics Committee of the School of Public Health, Tongji Medical College, and Dongfeng General Hospital, DMC. All participants provided written informed consent.
status and lifestyle was included in the questionnaires. The general health examination was performed at the same time. Standing height, body weight, waist circumference and hip circumference were measured with participants in light indoor clothing and without shoes. Body mass index (BMI) was calculated as weight in kilogrammes divided by height in metres squared. All subjects were examined in the morning after overnight fasting, and 15 mL of fasting blood was drawn with three vacuum (ethylenediamine tetraacetic acid) anticoagulation tubes for plasma and coagulation tube for serum. Blood glucose level was determined through Glucose Oxidase method by Abbott Aroset analyzer. Triglyceride, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were measured by the hospital’s laboratory with ARCHITECT Ci8200 automatic analyzer (ABBOTT Laboratories. Abbott Park, Illinois, USA) using the Abbott Diagnostics reagents according to the instructions of the manufacturer. Whole blood samples obtained from the participants were immediately assayed for HbA1c level with high-performance liquid chromatography (D-10 System; Bio-Rad Laboratories, Hercules, CA, USA). Helicobacter pylori status was measured via 14C urea breath test, a non-invasive test that was considered to be ‘gold standard’ technique for the detection of H. pylori infection [13]. Results were expressed as disintegrations per minute (dpm). Subjects with dpm ≥ 100 were considered to be infected with H. pylori; otherwise, they were defined not.
Assessment of covariates According to the respondents’ self-reported smoking status, participants were classified as ex-smokers, current smokers and nonsmokers. Based on the self-reported alcohol consumption status, participants were grouped as exalcohol, current alcohol and non-alcohol consumers. As the sample size of ex-smokers (12%) and ex-alcohol consumers (6%) was too small, we combined them into nonsmokers and non-alcohol consumers. Physical activity was presented as metabolic equivalent (MET) hours. MET hours per week were calculated on the basis of the following formula: MET coefficient of activity × duration (hours per time) × frequency (times per week). Other variables were dichotomized as yes or no according to the responses to questions on family history of diabetes and the use of oral hypoglycemic agent, insulin and antibiotics.
Data collection Definition of diabetes mellitus Baseline data were collected by trained interviewers via semi-structured questionnaire during face-to-face interviews. Information on sociodemographic factors, health Copyright © 2015 John Wiley & Sons, Ltd.
The diagnosis of diabetes mellitus was based on American Diabetes Association criteria [14] as meeting any of the Diabetes Metab Res Rev 2016; 32: 95–101. DOI: 10.1002/dmrr
Association of H. pylori and Diabetes
97
following criteria in follow-up interviews or laboratory examinations: (1) self-report of a physician’s diagnosis of diabetes, (2) fasting blood glucose level of ≥7.0 mmol/L and (3) usage of diabetes medication (insulin or oral hypoglycemic agent).
Data analysis All statistical analyses were performed using SPSS 13.0 software. Categorical variables were expressed in percentages and compared by Chi-squared analysis. Continuous variables were expressed in means ± standard deviation and compared by student’s t-test or analysis of variation unless otherwise specified. We computed the multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for diabetes mellitus by the logistic regression model. In multivariable model 1, we adjusted for age (continuous), sex (male/female), BMI (continuous) plus smoking status (yes/no), alcohol consumption status (yes/no) and family history of diabetes (yes/no). In multivariable model 2, we adjusted for the same set of variables as model 1 plus MET hours (continuous). Based on model 2, model 3 further included the use of antibiotics (yes/no). A two-side pvalue of
Helicobacter pylori infection is associated with type 2 diabetes among a middle- and old-age Chinese population
Xu Han1, Yaru Li1, Jing Wang1, Bing Liu1, Hua Hu1, Xiulou Li2, Kun Yang2, Jing Yuan1, Ping Yao1, Sheng Wei1, Youjie Wang1, Yuan Liang1, Xiaoping Miao1, Xiaomin Zhang1, Huan Guo1, Handong Yang2, Tangchun Wu1, Meian He1* 1
Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China
2
Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China *Correspondence to: Meian He, Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, Hubei, 430030, China. E-mail: [email protected]
Abstract Background Although the association of Helicobacter pylori (H. pylori) infection with diabetes mellitus has been evaluated, findings are controversial. This study investigated the association in a Chinese population. Methods A cross-sectional study, including a total of 30 810 subjects from the Dongfeng-Tongji Cohort study, was conducted. H. pylori status was measured via 14 C urea breath test. Association analysis was performed by logistic regression, with multivariable adjustment for sex, age, body mass index, smoking, alcohol consumption, family history of diabetes, physical activity and the use of antibiotics. Results Among a middle-age and old-age Chinese population, individuals with H. pylori infection also had a higher prevalence of type 2 diabetes (21.3% versus 20.2%, p = 0.026). H. pylori infection was associated with higher risk of type 2 diabetes [odds ratio, 1.08 (95% confidence interval: 1.02–1.14); p = 0.008] after adjustment for other confounders. The association was significant among women, those who were above 65 years old, not overweight or obese, and those who did not smoke, did not consume alcohol and without family history of diabetes. However, there was no interaction between H. pylori infection and other traditional risk factors on type 2 diabetes risk. Subjects with H. pylori infection had a lower level of high-density lipoprotein cholesterol (p < 0.0001) and higher levels of blood pressure (p < 0.001), total cholesterol, HbA1c and fasting blood glucose (p < 0.0001) than those who did not. Conclusions These findings suggested that H. pylori infection was associated with the risk of type 2 diabetes in a middle-age and old-age Chinese population. Copyright © 2015 John Wiley & Sons, Ltd. Keywords
Helicobacter pylori; type 2 diabetes; interaction
Introduction Received: 26 March 2015 Revised: 11 June 2015 Accepted: 1 July 2015
Copyright © 2015 John Wiley & Sons, Ltd.
The prevalence of diabetes mellitus has increased dramatically throughout the world, and the overall prevalence of diabetes was estimated to be 11.6% in the Chinese adult population [1]. Diabetes mellitus is a multifactorial disorder resulting from genetic, environmental, lifestyle and social factors. Environmental factors account for a high proportion in the complex pathogenesis of
X. Han et al.
96
diabetes mellitus [2]. Chronic infection constitutes one of the major environmental etiologic factors, and the effects of infectious agents have been studied. Helicobacter pylori (H. pylori) are gram-negative bacteria that colonize the human stomach, causing chronic gastritis, gastric malignancy and peptic ulcer disease, and have been recognized as a major public health concern all over the world [3]. The prevalence of H. pylori infection ranges from 41.35–72.3% and may fluctuate among the different population and different geographic areas [4]. H. pylori may have an influence on cardiovascular diseases and metabolic syndrome through the elevations in inflammatory cytokines levels such as C-reactive protein (CRP) and interleukin-6, which were also implicated in the pathogenesis of diabetes mellitus [5–7]. Previous studies have suggested H. pylori to be positively associated with diabetes mellitus [2,8,9]. However, other studies found no association between them [10,11]. Therefore, the relationship between H. pylori infection and the risk of diabetes mellitus still remains to be clearly defined. In this cross-sectional study including 30 810 participants from the Dongfeng-Tongji Cohort study, we assessed the association between H. pylori infection and the risk of type 2 diabetes as well as its traditional risk factors.
Materials and methods Study population The Dongfeng-Tongji Cohort study was launched in 2008 among retirees of Dongfeng Motor Corporation (DMC) in Shiyan City, Hubei province [12]. DMC was founded in 1969 and is one of the three largest auto manufacturers in China. After follow-up for the first time in 2013, we recruited a total of 38 295 retirees, and 34 708 retirees took physical examination and provided questionnaires. Data allowing the determination of both H. pylori and diabetes mellitus status were available for 30 810 of the participants after excluding those with missing data. The sociodemographic characteristics were similar between participants included in the present study and those excluded. The study has been approved by the Medical Ethics Committee of the School of Public Health, Tongji Medical College, and Dongfeng General Hospital, DMC. All participants provided written informed consent.
status and lifestyle was included in the questionnaires. The general health examination was performed at the same time. Standing height, body weight, waist circumference and hip circumference were measured with participants in light indoor clothing and without shoes. Body mass index (BMI) was calculated as weight in kilogrammes divided by height in metres squared. All subjects were examined in the morning after overnight fasting, and 15 mL of fasting blood was drawn with three vacuum (ethylenediamine tetraacetic acid) anticoagulation tubes for plasma and coagulation tube for serum. Blood glucose level was determined through Glucose Oxidase method by Abbott Aroset analyzer. Triglyceride, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were measured by the hospital’s laboratory with ARCHITECT Ci8200 automatic analyzer (ABBOTT Laboratories. Abbott Park, Illinois, USA) using the Abbott Diagnostics reagents according to the instructions of the manufacturer. Whole blood samples obtained from the participants were immediately assayed for HbA1c level with high-performance liquid chromatography (D-10 System; Bio-Rad Laboratories, Hercules, CA, USA). Helicobacter pylori status was measured via 14C urea breath test, a non-invasive test that was considered to be ‘gold standard’ technique for the detection of H. pylori infection [13]. Results were expressed as disintegrations per minute (dpm). Subjects with dpm ≥ 100 were considered to be infected with H. pylori; otherwise, they were defined not.
Assessment of covariates According to the respondents’ self-reported smoking status, participants were classified as ex-smokers, current smokers and nonsmokers. Based on the self-reported alcohol consumption status, participants were grouped as exalcohol, current alcohol and non-alcohol consumers. As the sample size of ex-smokers (12%) and ex-alcohol consumers (6%) was too small, we combined them into nonsmokers and non-alcohol consumers. Physical activity was presented as metabolic equivalent (MET) hours. MET hours per week were calculated on the basis of the following formula: MET coefficient of activity × duration (hours per time) × frequency (times per week). Other variables were dichotomized as yes or no according to the responses to questions on family history of diabetes and the use of oral hypoglycemic agent, insulin and antibiotics.
Data collection Definition of diabetes mellitus Baseline data were collected by trained interviewers via semi-structured questionnaire during face-to-face interviews. Information on sociodemographic factors, health Copyright © 2015 John Wiley & Sons, Ltd.
The diagnosis of diabetes mellitus was based on American Diabetes Association criteria [14] as meeting any of the Diabetes Metab Res Rev 2016; 32: 95–101. DOI: 10.1002/dmrr
Association of H. pylori and Diabetes
97
following criteria in follow-up interviews or laboratory examinations: (1) self-report of a physician’s diagnosis of diabetes, (2) fasting blood glucose level of ≥7.0 mmol/L and (3) usage of diabetes medication (insulin or oral hypoglycemic agent).
Data analysis All statistical analyses were performed using SPSS 13.0 software. Categorical variables were expressed in percentages and compared by Chi-squared analysis. Continuous variables were expressed in means ± standard deviation and compared by student’s t-test or analysis of variation unless otherwise specified. We computed the multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for diabetes mellitus by the logistic regression model. In multivariable model 1, we adjusted for age (continuous), sex (male/female), BMI (continuous) plus smoking status (yes/no), alcohol consumption status (yes/no) and family history of diabetes (yes/no). In multivariable model 2, we adjusted for the same set of variables as model 1 plus MET hours (continuous). Based on model 2, model 3 further included the use of antibiotics (yes/no). A two-side pvalue of
