Abstract
Helicobacter pylori (H pylori) infection was common worldwide and previous researches on the correlation between H pylori infection and metabolic abnormality provided inconsistent conclusions. We assessed acute H pylori infection prevalence and the relationship with metabolic abnormality in general Chinese population. Participants attending for the physical examination underwent a carbon-13 urea breath test. For individual, the following data were collected: age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, total protein, albumin, globulin (GLB), total bilirubin, direct bilirubin (DBIL), indirect bilirubin, alanine transaminase, glutamyl transpeptidase, alkaline phosphatase, cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, urea nitrogen, creatinine, uric acid, fasting plasma glucose (FPG), and homocysteine. A total of 29,154 participants were enrolled. The prevalence of acute H pylori infection was 29.79% (8684/29,154). Spearson correlation analysis showed that gender, BMI, ALB, GLB, total bilirubin, DBIL, indirect bilirubin, and FPG were closely related to H pylori infection. Multinomial logistic regressions analysis with stepwise subset selection further identified gender, BMI, ALB, GLB, DBIL, and FPG as independent risk factors for acute H pylori infection. Our results indicated that acute H pylori infection might has a significant impact on metabolic abnormalities, which should be further confirmed.
Keywords: albumin, body mass index, direct bilirubin, fasting plasma glucose, globulin, Helicobacter pylori
1. Introduction
Helicobacter pylori (H pylori) infection was a global public health problem, with higher burdens in the developing countries.[1,2] Nevertheless, epidemiological researches in China yielded inconsistent conclusion.[3] At the same time, the prevalence of H pylori infection in China might be diverse among different ethnics and different regions. For example, a meta-analysis by Bai D et al showed the pooled H pylori infection prevalence was 62.2% versus 55.3% among Tibetans and Hans, respectively.[4] Recently, a large-scale, national, family-based epidemiological study demonstrated family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces in mainland China, with an average rate of 71.21%.[5] Therefore, it is necessary to further explore the acute prevalence of Helicobacter pylori infection in specific area in China, especially in general population.
On the other hand, in the past decades, it is well established that H pylori was the most prevalent pathogenic bacteria in the stomach and could lead to a wide array of gastric disorders and gastrointestinal microecology, including chronic gastritis, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid tissue lymphoma.[6,7] Subsequently, increasing evidence suggested H pylori infection might be causally linked to a variety of extra-gastric diseases and metabolic derangements.[8,9] However, previous researches on the correlation between H pylori infection and metabolic abnormality provided conflicting results. Through the analysis of 3037 persons aged 32 to 82 years, Wawro N et al found no association between H pylori seropositivity and body mass index (BMI), metabolic diseases(type 2 diabetes, hypertension and dyslipidemia, gout or increased uric acid).[10] On the contrary, another study observed that, when compared with H pylori-positive individuals, fasting plasma glucose (5.36 ± 1.20 vs 5.25 ± 1.03, P = .043) and postprandial blood sugar (7.21 ± 2.50 vs 6.96 ± 2.29, P = .035) were significantly lower in the H pylori-negative group, respectively.[11] Moreover, only in male subjects, H pylori infection was significantly associated with the presence of metabolic syndrome (OR = 1.26, 95% CI: 1.00–1.57) and DM (OR = 1.59, 95% CI: 1.17–2.17).[12] So, it is important to further clarify the correlation between H pylori infection and metabolic abnormality.
Here, we performed a retrospective study to evaluate acute H pylori infection prevalence in general Chinese population and to determine whether H pylori infection was associated with metabolic abnormality.
2. Materials and methods
2.1. Study participants
This work was conducted with a retrospective design and the participants attending the health promotion center of Zhejiang hospital for evaluation of regular health were analyzed from January 2021 to December 2022. It was approved by the Medical Ethics Committee of Zhejiang Hospital (2023-78K).
2.2. Inclusion and exclusion criteria
The main inclusion criteria included: completing carbon-13 urea breath test (13C-UBT) and biochemical laboratory test, not using proton pump inhibitors, histamine type 2 receptor antagonists, antibiotics, bismuth, or sucralfate for up to 1 month prior to the urea breath test.
Individuals who had received H pylori eradication therapy, or antibiotics were excluded.
2.3. Diagnosis of active H pylori infection
After an overnight fast, 13C-UBT was performed using the Urea [13C] Capsule Breath Test Kit (Shenzhen Zhonghe Headway Bio-Sci & Tech Co., Ltd., China), according to the manufacturer’s instructions. The results were expressed as delta over baseline.
2.4. Covariates measurement
BMI was estimated based on a general formula in which the weight in kilo-grams was divided by the square of the height in meters (kg/m2) of a participant. Systolic, diastolic blood pressure were obtained from the right arm using a portable digital sphygmomanometer (HEM-7000-E, Omron, Kyoto, Japan).
After an overnight fast, biochemical laboratory data, including total protein, albumin, globulin (GLB), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin, alanine transaminase, glutamyl transpeptidase, alkaline phosphatase, cholesterol, triglyceride (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, urea nitrogen, creatinine, uric acid, fasting plasma glucose (FPG), and homocysteine, were determined by AU Chemistry Systems (Beckman Coulter AU5800, Beckman Coulter Ireland Inc.).
2.5. Statistical analysis
Chi-square analysis and the Mann–Whitney U test were performed to compare categorical variables and continuous variables, respectively. Correlation analysis was performed using Spearman correlation test. Then, significant variables in the correlation test (P < .05) were tested by a multinomial logistic regressions analysis with stepwise subset selection to identify independent factors for H pylori infection. All statistical analyses were completed using the SPSS 21.0 software package. P < .05 was considered statistically significant.
3. Results
3.1. Prevalence of acute H pylori infection in general Chinese population
From January 2021 to December 2022, a total of 69,970 persons attended the health promotion center of Zhejiang hospital for health examination. Among them, 29,154 participants completing 13C-UBT and biochemical laboratory test were enrolled, including 16,969 males (58.20 %) and 12,185 females (41.80 %). The prevalence of acute H pylori infection was 29.79% (8684/29,154). And, men (31.37%, 5374/16,969) were more prone to suffering from H pylori infection than women (21.16%, 3310/12,185). The characteristics classified by H pylori-positive or H pylori-negative were summarized in Table 1.
Table 1.
Comparison of clinical parameters based on H pylori infection status.
| Clinical data | H pylori (−) | H pylori (+) | P value | |
|---|---|---|---|---|
| Gender (male: female) | 11,595:8875 | 5374:3310 | <.001 | |
| Age (year) | 45.26 ± 14.36 | 46.84 ± 14.66 | <.001 | |
| BMI (kg/m2) | 23.58 ± 3.53 | 23.94 ± 3.42 | <.001 | |
| SBP (mm Hg) | 123.51 ± 16.76 | 125.40 ± 17.33 | <.001 | |
| DBP (mm Hg) | 75.32 ± 12.23 | 76.47 ± 11.00 | <.001 | |
| Lab data | Total protein(g/L) | 73.32 ± 4.49 | 73.37 ± 4.70 | .457 |
| ALB (g/L) | 44.40 ± 2.74 | 44.22 ± 2.78 | <.001 | |
| GLB (g/L) | 28.91 ± 3.54 | 29.15 ± 3.88 | <.001 | |
| TBIL(μmol/L) | 15.24 ± 5.92 | 15.15 ± 5.93 | .145 | |
| DBIL (μmol/L) | 2.7 ± 1.05 | 2.66 ± 1.07 | .001 | |
| IBIL (μmol/L) | 12.54 ± 4.99 | 12.48 ± 4.99 | .283 | |
| ALT (U/L) | 25.66 ± 21.48 | 27.00 ± 27.61 | <.001 | |
| GGT (U/L) | 31.92 ± 33.53 | 34.98 ± 40.60 | <.001 | |
| ALP(U/L) | ±65.92 | 198.77 ± 63.63 | <.001 | |
| FPG (mmol/L) | 5.34 ± 1.08 | 5.45 ± 1.24 | <.001 | |
| Urea nitrogen (mmol/L) | 5.02 ± 1.26 | 5.07 ± 1.35 | .134 | |
| Creatinine (μmol/L) | 72.76 ± 16.04 | 74.21 ± 17.79 | <.001 | |
| Uric acid (μmol/L) | 357.4 ± 89.71 | 365.66 ± 92.36 | <.001 | |
| Triglyceride (mmol/L) | 1.58 ± 1.36 | 1.68 ± 1.48 | <.001 | |
| Cholesterol (mmol/L) | 5.04 ± 1.00 | 5.08 ± 1.00 | <.001 | |
| HDL-C (mmol/L) | 1.36 ± 0.33 | 1.32 ± 0.33 | <.001 | |
| LDL-C (mmol/L) | 2.95 ± 0.83 | 2.99 ± 0.82 | <.001 | |
| Homocysteine (μmol/L) | 11.87 ± 6.15 | 12.68 ± 7.00 | <.001 | |
ALB = albumin, ALP = alkaline phosphatase, ALT = alanine transaminase, BMI = body mass index, DBIL = direct bilirubin, DBP = diastolic blood pressure, FPG = fasting plasma glucose, GGT = glutamyl transpeptidase, GLB = globulin, HDL-C = high-density lipoprotein cholesterol, IBIL = indirect bilirubin, LDL-C = low-density lipoprotein cholesterol, SBP = systolic blood pressure, TBIL = total bilirubin.
3.2. Correlation analysis between H pylori infection and clinical parameters
First, Spearson correlation analysis was employed to find the relationship between clinical parameters, including metabolic indicators, and H pylori infection. As shown in Table 2, gender, BMI, ALB, GLB, TBIL, DBIL, indirect bilirubin, and FPG were closely related to acute H pylori infection.
Table 2.
Correlation analysis between H pylori infection and clinical data.
| H pylori infection | ||
|---|---|---|
| r | P value | |
| Gender | 0.023 | <.001 |
| Age (year) | −0.003 | .615 |
| BMI (kg/m2) | −0.018 | .007 |
| SBP (mm Hg) | −0.003 | .652 |
| DBP (mm Hg) | 0.001 | .916 |
| Total protein (g/L) | 0.012 | .06 |
| ALB (g/L) | −0.014 | .036 |
| GLB (g/L) | −0.026 | <.001 |
| TBIL (μmol/L) | −0.024 | <.001 |
| DBIL (μmol/L) | −0.023 | .001 |
| IBIL (μmol/L) | −0.024 | <.001 |
| ALT (U/L) | −0.003 | .661 |
| GGT (U/L) | −0.005 | .432 |
| ALP (U/L) | −0.008 | .246 |
| FPG (mmol/L) | 0.013 | .043 |
| Urea nitrogen (mmol/L) | −0.005 | .485 |
| Creatinine (μmol/L) | −0.008 | .2 |
| Uric acid (μmol/L) | −0.008 | .232 |
| TG (mmol/L) | −0.009 | .153 |
| Cholesterol (mmol/L) | 0.002 | .738 |
| HDL (mmol/L) | <0.001 | .988 |
| LDL (mmol/L) | 0.005 | .471 |
| Homocysteine (μmol/L) | −0.005 | .744 |
ALB = albumin, ALP = alkaline phosphatase, ALT = alanine transaminase, BMI = body mass index, DBIL = direct bilirubin, DBP = diastolic blood pressure, FPG = fasting plasma glucose, GGT = glutamyl transpeptidase, GLB = globulin, HDL-C = high-density lipoprotein cholesterol, IBIL = indirect bilirubin, LDL-C = low-density lipoprotein cholesterol, SBP = systolic blood pressure, TBIL = total bilirubin.
3.3. Identifying independent risk factors for H pylori infection
Then, we used a multinomial logistic regressions analysis with stepwise subset selection to further identify potential factors for acute H pylori infection. In our model, gender, BMI, ALB, GLB, DBIL, and FPG were identified as independent risk factors for H pylori infection (presented in Table 3). After stratified analysis by gender, BMI, ALB, GLB, DBIL, and FPG were identified as independent risk factors for H pylori infection in female. Whereas, only BMI, ALB, DBIL, and FPG were identified as independent risk factors for acute H pylori infection in male (data not shown).
Table 3.
Multivariate logistic analysis of risk factors for H pylori infection.
| Parameters | Regression coefficient | Adjusted OR (95% CI) | P value |
|---|---|---|---|
| Gender | −0.248 | 0.780 (0.730–0.834) | <.001 |
| BMI (kg/m2) | 0.016 | 1.016 (1.007–1.025) | .001 |
| ALB (g/L) | −0.021 | 0.979 (0.969–0.990) | <.001 |
| GLB (g/L) | 0.018 | 1.018 (1.010–1.027) | <.001 |
| DBIL (μmol/L) | −0.044 | 0.957 (0.930–0.984) | .002 |
| FPG (mmol/L) | 0.062 | 1.064 (1.038–1.091) | <.001 |
ALB = albumin, BMI = body mass index, DBIL = direct bilirubin, FPG = fasting plasma glucose, GLB = globulin.
4. Discussion
UBT, including 13C-UBT and 14C-UBT, was the best recommended noninvasive test in the test-and-treat strategy and verifying test after eradication. Between these 2 methods, the 13C-UBT, adopted in the present work, was the better approach to diagnose H pylori infection because of its simplicity, high accuracy, and being less affected by focal distribution of H pylori.[13] The prevalence of acute H pylori infection in general population was 29.79% in the study, which was similar to the results of Lu LJ et al.[11] However, regarding to sex difference, it was 31.37 % in males and 21.16 % in females, which were higher than Taiwan general population.[12] The reasons for this discrepancy might be related to the geographical location, educational level, and economic status of the subjects.[10]
In our study, the main metabolic abnormalities in patients with H pylori infection included: 1. elevated BMI, GLB, FPG levels; 2. decreased serum ALB and DBIL concentration. Consistent with our results, Liu H et al found that H pylori infection was significantly associated with lower serum ALB levels, elevated GLB levels, and lower ALB/GLB ratio.[14] In addition, H pylori infection was independently associated with lower DBIL levels (OR = 1.497, 95%CI = 1.121–1.999, P = .006) or TBIL levels (OR = 1.322, 95%CI = 1.005–1.738, P = .046) after adjustment for age, sex, BMI, alanine transaminase, AST, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TC and TG.[15]
The underlying mechanism by which H pylori infection increase GLB and decrease ALB level was not fully understood. The possible mechanisms could be summarized as follows. First, when a foreign microbe, like H pylori, was present in the body, the immune organs of the body activate the immune mechanism to increase GLB in order to destroy the invaders.[16] Second, H pylori infection might reduce ALB levels by increasing gastric pH and thereby affecting gastric digestion and absorption.[17] Finally, due to the indirect damage to the urinary system by systemic inflammatory immune response induced by H pylori infection and direct damage to the urinary system by virulence factors released by H pylori, it could promote the formation of microproteinuria leading to a decrease in serum ALB level.[18]
H pylori infection had been shown to result in chronic inflammation and influence of bile reflux,[19,20] which might at least in part explain the bilirubin changes, but further research relating to possible mechanisms was required.
Our case–control study also found an association between acute H pylori infection and elevated FPG. Nevertheless, there was no agreement among researchers on the relationship between acute H pylori infection and blood sugar level/diabetes.[21–23] The mechanism of this relationship might partly due to insulin resistance.[24,25] However, it had not been fully elucidated so far.
Hypertension was a substantial factor for the development of atherosclerosis, with a high incidence and prevalence that continued to increase and contributed to worldwide morbidity and mortality.[26] It is reported that chronic H pylori infection led to disturbed immune reactions and inflammation, which ultimately contribute to hypertension.[27,28] However, the impact of H pylori infection on hypertension obtained conflicting results. For example, Wan Z et al[29] found the individuals with H pylori infection had a higher prevalence of hypertension(57.5% vs 55.1%, P = .002), and infection rate of H pylori in patients with hypertension was higher than that in non-hypertensive individuals (48.8% vs 46.4%, P = .002).[30] Moreover, H pylori eradication has been reported to improve arterial hypertension.[31] In contrast, our present study showed that, after adjusting for confounding factors, H pylori infection was not associated hypertension, which was in line with the results from Tang H et al and Liu L et al.[32,33]
The current study had relatively large sample size, to date. Moreover, it covered participants of different ages and different gender. However, there were some limitations. First, it was a retrospective, observational association study, which tended to leave uncertainty. Second, it lacked clinical outcome, including survival time, etc. Finally, the participants were heterogeneous, with diversities of medication and different morbidity, which might confound the results.
In conclusion, our study showed that the prevalence of acute H pylori infection was 29.79%, and that gender, BMI, ALB, GLB, DBIL, and FPG were independent risk factors for H pylori infection. However, more prospective randomized controlled study should be done to further confirm it.
Author contributions
Conceptualization: Qing Wu.
Data curation: Zhan Feng, Qing Wu, Fan Xu.
Formal analysis: Lan Chen, Qing Wu.
Investigation: Fan Xu.
Methodology: Guofu Wang.
Software: Qian Tong.
Validation: Qian Tong.
Writing – original draft: Lan Chen, Qian Tong.
Writing – review & editing: Guofu Wang.
Abbreviations:
- 13C-UBT
- carbon-13 urea breath test
- BMI
- body mass index
- DBIL
- direct bilirubin
- FPG
- fasting plasma glucose
- GLB
- globulin
- H pylori
- Helicobacter pylori
- TBIL
- total bilirubin
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Feng Z, Chen L, Wu Q, Xu F, Tong Q, Wang G. Acute Helicobacter pylori infection prevalence and association with metabolic abnormality in general Chinese population: A retrospective study. Medicine 2024;103:12(e37117).
Contributor Information
Zhan Feng, Email: 1269666@qq.com.
Lan Chen, Email: chenl70817@163.com.
Qing Wu, Email: aaiwuqing@126.com.
Fan Xu, Email: 165553273@qq.com.
Qian Tong, Email: 1169198943@qq.com.
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