Distribution of Helicobacter pylori infection and abnormal body-mass index ( BMI ) in a developing country

Introduction: Helicobacter pylori is prevalent in developing nations. We determined the prevalence of H. pylori infection in relation to bodymass index (BMI) of dyspeptic patients and related comorbid conditions. Methodology: In a cross-sectional study, dyspeptic patients were enrolled and tested for H. pylori infection. “Underweight” was defined as BMI lower than 18.4; “Healthy” 18.5 to 23; “Overweight” 23.1-27.9; and “Obese” greater than 28. Results: Six hundred and ninety-eight patients were included, with a mean age of 44 ± 16 years. Males were 373/698, 53%. H. pylori was positive in 399/698, 57%. Underweight were 36 (5%); BMI-healthy 168 (24%); overweight 236 (34%) and obese 258 (37%). H. pylori infection was present in 65/273 BMI-healthy patients ; 24% compared to obese 208/273; 76% (P < 0.001). In the H. pyloripositive with a “healthy” BMI, dyslipidemia was seen in 6/65; 8% compared to obese 53/208; 25% (P = 0.005); type 2 diabetes in 8/65; 12% with a “healthy” BMI compared to obese 54/208; 26% (P = 0.022) and coronary artery disease in 4/65; 6% of BMI-healthy compared to obese 38/208; 18% patients (P = 0.018). Multivariate analysis showed that age 31-50 years (OR 1.77, 95% CI 1.13-2.77), BMI > 23.1 (OR 2.91, 95% CI infection. 2.014.20), and type 2 diabetes (OR 2.41, 95% CI 1.43-4.06) were risk factors for H. pylori Conclusions: H. pylori infection was prevalent in the 31-50-year age group. Abnormal BMI was associated with H. pylori infection.


Introduction
Helicobacter pylori (H.pylori) is a Gram-negative spiral-shaped microaerobic microorganism that is prevalent in developing Asian countries [1].It is associated with gastritis, peptic ulcer, gastric carcinoma and lymphoma [2][3][4].Extragastric manifestations of H. pylori infection are cardiovascular, hematological, immunological and dermatological [5][6][7].H. pylori has a feco-oral route of transmission and is prevalent in people living in crowded conditions and having a poor socioeconomic status [8].H. pylori infection has decreased in the developed world i.e.United States, Western Europe and in some Asian countries such as Japan, etc. H. pylori was detected in 58% of children at the age of 15 years in Pakistan [9].It tends to increase with age and in people with low socioeconomic status [9].
Obesity has increased rapidly worldwide in the past few years, particularly in developing countries.Urbanization, lifestyle changes and an unhealthy energy-dense diet, contribute to obesity in our country, where one-in-four adult is overweight [10].Obesity is a non-communicable disease that is linked to microbiome in animals and humans.Obesity is associated with impaired immune response [11,12].Recent studies of H. pylori and obesity have revealed that obese individuals have a higher prevalence of H. pylori infection [11,12].A systematic review showed that insulin resistance accompanying obesity was positively related to H. pylori infection [13].In contrast, another study looking at the association between body-mass index (BMI) and H. pylori infection, was negative [14].An inverse correlation between obesity and H. pylori has been also described [15].On the other hand, an increase of weight has been observed following eradicationof H. pylori [16].Therefore, the evidence of the role of H. pylori infection in human obesity is inconclusive and controversial [17].These contradictory reports suggest a need to study further the relationship between obesity and H. pylori infection.Obesity is a public health problem in our country.It is also associated with hypertension, dyslipidemia and cardiovascular disease.A higher prevalence is not restricted to urban population [10].In this study, we determined the prevalence of H. pylori infection in relation to BMI of dyspeptic patients and the association between comorbid conditions such as hypertension, type 2 diabetes, dyslipidemia and coronary artery disease, and H. pylori infection.

Methodology
The study was conducted among adults who attended the gastroenterology clinic for dyspeptic symptoms that included abdominal discomfort or pain, bloating and nausea, and underwent gastroscopy from January 2015 to December 2016 at a tertiary care centre.Data were collected on anthropometric measurements, complete blood count, fasting blood hemoglobin A1c, lipid profile i.e. serum cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol, and the results of the H. pylori test.The study was reviewed and approved by the ethics committee.After enrolment, medicalhistory was taken and physical examination and base-line tests were performed.Height in meters and weight in kilograms were recorded.BMI was calculated as weight in kilograms divided by the square of height in meters.Modified criteria of BMI calculation was used for South Asians [18], as they have different associations between BMI, percentage of body fat and health risks than Europeans [18]."Underweight" was defined as BMI lower than 18.4; "Healthy" 18.5 to 23; "Overweight" 23.1-27.9;and "Obese" greater than 28.The criterion used for type 2 diabetes was fasting plasma glucose (FPG) level of 7. 0 mmol/L [19].Blood pressure was recorded using an automated sphygmomanometer.Criterion used for hypertension was value greater than 140/90 mm Hg as defined by the JCN 7 (Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure) [20].Dyslipidemia was defined according to the National Cholesterol Education Program (NCEP) ATP III Guideline for serum cholesterol > 200mg/dl; triglycerides > 200mg/dl; HDL < than 40mg/dL; LDL > than 160mg/dL and VLDL cholesterol > 30mg/dL [21].Coronary artery disease included angina (stable and unstable), myocardial infarction, and sudden cardiac death [22].The inclusion criteria were adults over 18 years of age with dyspepsia for more than six months.Patients who were on antibiotics (in the last 2 months), acid reducing drugs such as histamine-2 receptor blockers and proton pump inhibitors (in the last 2 weeks) were excluded from having C-14 Urea Breath Test for H. pylori infection.Pregnant and lactating females, patients with inflammatory bowel disease, celiac disease, and those not willing to participate were excluded.Written informed consent was obtained for gastroscopy.All participants received written and verbal information about the study.Six hundred and ninety-eighty patients with a history of dyspepsia for the previous 6 months underwent either gastroscopy with biopsy and histological examination, or 13 C-urea breath test ( 13 C-UBT), or H. pylori stool antigen (HpSA) test [23][24].Patients were diagnosed as H. pylori infection-positive if any of these tests was positive.Written informed consent was obtained from all participants.

Statistical analysis
Statistical analysis was carried out with the SPSS version 16.0 software program.Results were expressed as mean ± standard deviation.Univariate analysis was carried out using the chi-square test and a multivariate analysis by regression analysis.P-value of < 0.05 was statistically significant.

Results
There were 373 (53%) male patients and 325 (47%) female.Their age ranged from 18 to 90 years with a mean age of 44 ± 16 years.The age range of males was 18-85 years and of females 18-90 years.H. pylori infection was detected in 399 (57%).The mean age and standard deviation (SD) of the two groups of patients were similar.The mean age of the BMI-healthy was 38.4 ± 18 years.There was a significant difference between the mean age of overweight and obese vs underweight (P = 0.005) and vs healthy (P < 0.001), respectively.A total of 41 (6%) were smokers and 100 (14%) consumed alcohol.Co-morbid conditions included coronary artery disease in 89 (13%), hypertension in 89 (13%), type 2 diabetes in 100 (14%) and dyslipidemia in 105 (15%).
H. pylori infection prevalence was high in up to 50 years of age and reduced in the sixth decade (Table 1 2).

Discussion
The study showed that the prevalence of H. pylori infection was lower in patients who were underweight compared to BMI-healthy or with a higher BMI.The number of underweight patients was small.In this study, H. pylori infection did not show any gender distribution (Table 1).A previous study demonstrated that males who were H. pylori infection-positive had higher LDL cholesterol levels and significantly lower HDL cholesterol levels than the H. pylori-negative [25].Our study did not show similar results.We did not have many patients who were smokers or consumed alcohol to analyze H. pylori infection in relation to these social habits.H. pylori infection in subjects defined as BMIhealthy, overweight and obese, was 16%, 29%, and 51%, respectively.Our subjects, with a mean age of 44 years, were younger than in a previous study [14].In this study, overweight and obese patients had a higher rate of H. pylori infection compared to the BMI-healthy individuals (Table 1).These findings are important, as adverse health outcomes are known to be associated with overweight and obesity.
H. pylori initiates a low-grade inflammation that induces mechanisms leading to expression of virulence peptides that resemble host antigens.The stimulated host immune responses include gastric epithelial cytokine secretion; H. pylori increases the levels of tumour necrosis factor-alpha and other cytokines that promote inflammation [26].Host immunological reaction is unable to clear H. pylori infection which persists as a chronic infection.H. pylori infection could induce insulin resistance, disturb glucose and lipid homeostasis, and metabolism of adipocytokines [27].It increases serum levels of triglycerides, cholesterol, LDL cholesterol, apolipoproteins B, and decreases apolipoprotein A and HDL cholesterol levels [28][29].Undesirable abnormalities induced by H. pylori may increase the risk of cardiovascular disease especially in diabetic patients [30].In a previous study, H. pylori infection was demonstrated in 57% of the obese group, which was higher than the 27% in the control group [25].Another study, however, did not show increased H. pylori infection among overweight/obese young individuals as reported previously [31].These patients might have been exposed to bacteria other than H.pylori that may have altered the gastrointestinal microflora constitution that contributed to obesity.There is a constant interplay between diet, gut microbiome and host health status.Gut microbiome and H. pylori are reported to be associated with obesity [32,33].H. pylori and gut microbiota have an effect on the host's metabolism.Obesity is associated with an increased susceptibility to infection by different pathogens [34].There is an impaired immune function which increases with the grade of obesity [35].Various cellular changes involving immunological cells include a low maturation of monocytes into macrophages and reduced bactericidal activity of polymorphonuclear cells in obese subjects [36][37].Obese individuals also demonstrate a decrease in natural killer cell activity [38].Type 2 diabetics are prone to chronic infections.An association between H. pylori infection and type 2 diabetes (P = 0.001) was demonstrated in our study (Table 1).
South Asian people frequently do not appearto be overweight as compared to other ethnic groups.However, they have a tendency for central obesity that leads to storing of fat around their stomach [18].Central obesity is linked to an inherited gene and higher rate of diabetes and acute coronary syndrome [18].The prevalence of overweight and obesity has increased in recent years in Pakistan [10].The obesity epidemic is taking place in developing countries and is not necessarily driven by changes of H. pylori prevalence [39].H. pylori infection is prevalent in patients with above-normal BMI in the 31-50-year age group.There is a temporal association between H. pylori and patients with above-normal BMI.However, chronic H. pylori infection effect is not the only explanation for our results.

Conclusion
There was a low H. pylori infection in adults with low BMI and ahigher prevalence in obese compared to those with a normal BMI and the overweight.H. pylori infection in obese was significantly associated with coronary artery disease, type 2 diabetes and dyslipidemia in our population.A large communitybased study is recommended in order to further understand these associations at general population level.

Table 1 .
Association of Helicobacter pylori with body-mass index.

Table 2 .
Multivariate analysis of risk factors predicting H. pylori infection.
P value < than 0.05 was significant.