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Association Between Low Muscle Mass and Gastric Hyperplastic and Inflammatory Polyps in Chinese Asymptomatic Adult Males

Background Gastric polyp is an abnormally proliferative or neoplastic growth of the gastric mucosa, with a degree of tendency to transform into gastric cancer. Lack of physical activity that is significantly related to low muscle mass (LMM) and muscle strength has been identified to be associated with gastric polyps. In this study, we examine the association of LMM and different histological types of gastric polyps among Chinese asymptomatic adult males. Methods In total, 1,742 male adults undergoing bioelectrical impedance analysis and upper gastrointestinal endoscopies were included. Univariate and multivariate logistic regression models were used to analyze the effect of LMM on the risk of gastric polyps and different histological types. Results By univariate and multivariate analyses, LMM (OR: 1.689, 95%CI: 1.046–2.726, p = 0.032) kept independent effect on risk of gastric polyps. When ratio of appendicular skeletal muscle mass to body mass index(ASM/BMI) was brought into the analyses, it was identified to be negatively correlated with occurrence of gastric polyps (OR: 0.744, 95%CI: 0.566–0.977, p = 0.033). For different pathological types, LMM showed different effect on occurrence of gastric polyps. LMM was an independent indicator for hyperplastic and inflammatory polyps (OR: 2.378, 95%CI: 1.288–4.389, p = 0.006), rather than fundic gland polyps (OR: 1.013, 95%CI: 0.473–2.173, p = 0.973). Conclusion In general, LMM was an independent indicator for hyperplastic and inflammatory polyps occurrence in Chinese asymptomatic adult males.


INTRODUCTION
Gastric polyp is an abnormally proliferative or neoplastic growth of the gastric mucosa, protruding into the lumen of stomach (1), with a degree of tendency to transform into gastric cancer (2). The incidence of gastric polyps varies between 1 and 6% in individuals who undergo upper gastrointestinal endoscopies (3)(4)(5)(6). The most common subtypes of gastric polyps are fundic gland polyp, hyperplastic or inflammatory polyp, and adenomatous polyp (7).
A number of variables have been identified to have an impact on the risk of gastric polyps, such as age, gender, the incidence of Helicobacter pylori infection, use of proton pump inhibitors (PPIs), and physical activity (8)(9)(10). Females have a higher risk of gastric polyps (11,12), so males with gastric polyps have received little attention. Additionally, research by Wang et al. (10) proposed that lack of regular exercise was significantly associated with gastric polyps. Reduction in physical activity was significantly related to low muscle mass (LMM), namely sarcopenia (13). It was speculated that LMM might be associated with gastric polyps. However, there were no such research about the connection between LMM and gastric polyps. To address this issue, the aim of this study was to determine whether LMM was related to gastric polyps and different histological types in Chinese adult males.

METHODS
We conducted a cross-sectional study of Chinese adult males having a health-check in the First Affiliated Hospital of Wenzhou Medical University between January 2018 and June 2018.

Study Population
Inclusion criteria included: (1) males aged 18 years or older and (2) individuals who underwent bioelectrical impedance analysis

Data Collection
Baseline characteristic were collected by predesigned questionnaires, including age, gender, alcohol and smoking consumption, comorbidities, and histories of medication and surgery.
Smoking status was classified into 3 types: non-smoker (has never smoked before), past smoker (has quit for at least 2 yeas), and current smoker (is still smoking until the day of health-check or quit < 2 years). Males with alcohol consumption >140 g per week were regarded as heavy drinkers. Comorbidities were obtained by questionnaire and measurement, including hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and metabolic syndrome (MS). The blood pressure measurement, blood detection, and 13 C-urea breath test were performed on the morning of the health-check. The following blood measurements were tested: serum lipid profile, fasting blood glucose, and glycated hemoglobin. The BIA and upper gastrointestinal endoscopy were performed in each individual. The appendicular skeletal muscle mass (ASM, kg) was measured by BIA (InBody770; InBody Korean Inc.). The ASM (kg)/BMI (kg/m 2 ) was calculated to evaluate the muscle mass. According to the Foundation for the National Institutes of Health (FNIH) (14,15), males with ASM/BMI <0.789 m 2 were regarded as having low skeletal muscle mass. The endoscopic characteristics of polyps were recorded and analyzed, including existence, location, number, and size of pathological diagnosis. Helicobacter Pylori infection was detected by histopathological result of biopsied stomach specimen or 13 C-urea breath test.

Statistical Analysis
Category variables were compared by Pearson χ 2 tests and displayed as frequencies (percentages). The normal distribution All statistical analyses were carried out using R version 3.6.1 (https://www.r-project.org/). All analyses were two-tailed, with p < 0.05 considered significant.

Baseline Characteristics
We included 1,742 males, 1,487 of whom were in the group without LMM and 255 of them in the group with LMM ( Table 1). The median of ASM/BMI was 0.903, range from 0.555 to 1.934. One hundred and ten males were diagnosed with gastric polyps ( Table 2), with an incidence rate of 6.31%. There were three pathological types: fundic gland polyps (N = 54), hyperplastic and inflammatory polyps (N = 53), and adenomatous polyps (N = 1). The histology was not available on two individuals because of unsuitable biopsy specimens.

Univariate and Multivariate Analyses for Gastric Polyps
As

Univariate and Multivariate Analyses for Different Histological Types of Gastric Polyps
In univariate analysis (Supplementary

Different ASM/BMI in Individuals With and Without Gastric Polyps
As Figure 1 showed, individuals with and without gastric polyps displayed significantly different ASM/BMI (p = 0.032). Individuals with hyperplastic and inflammatory polyps showed relatively lower ASM/BMI (p = 0.010) compared to individuals without hyperplastic and inflammatory polyps. However, this association was not observed in fundic gland polyps (p = 0.959).
In individuals with age ≥ 50 (p = 0.028) and individuals without HP infection (p = 0.016), ASM/BMI was still significantly different between individuals with and without gastric polyps (Figure 2). Similarly, in individuals with age ≥ 50 (p = 0.028) and individuals without HP infection (p = 0.015), ASM/BMI was significantly higher in individuals without hyperplastic and inflammatory polyps (Figure 3).

DISCUSSION
In this study, we found an association between LMM and increased occurrence of hyperplastic and inflammatory polyps  Frontiers in Medicine | www.frontiersin.org in asymptomatic males. Up to now, there has been no research concerning the relation between reduced muscle mass and occurrence of gastric polyps. However, the inverse associations between physical activity and the presence of colorectal polyps, adenomas, and even cancer have been previously reported (16)(17)(18)(19)(20)(21). A study by Wang et al. (10) mentioned that lack of physical exercise was significantly associated with gastric polyps. Physical inactivity was a major cause of sarcopenia, which manifested as reduced muscle mass and strength (22). There might be an underlying connection between low muscle mass, gastric polyps, and physical inactivity. A relevant mechanism study about the relationship is needed in the future.
The population enrolled in this study was Chinese asymptomatic adult males. Moreover, we included 1,100 females and discovered that there was no connection between LMM and gastric polyps with p-value of 0.168 (Supplementary Table 4). Sarcopenia and gastric polyps are more common in females (23,24). But the correlation between low muscle mass and gastric polyps was found to exist in males in this study. It was inferred that sex hormones were responsible for the gender-specific difference. A further study about the underlying mechanism of gender-specific correlation between low muscle mass and gastric polyps is needed in the future.
The pathological types of gastric polyps in our study found to be associated with low muscle mass was hyperplastic or inflammatory polyps. It was caused by hyperplasia of foveolar cells accompanied by their increased exfoliation (25,26). Gastric hyperplastic or inflammatory polyps commonly reside in gastric mucosa with longstanding Helicobacter Pylori infectionassociated atrophy or metaplasia (25). In a study by Baeg et al. (27) it was discovered that Helicobacter Pylori eradication treatment increased ghrelin secretion and reduced the risk of low muscle mass. Thus, the correlation between gastric hyperplastic or inflammatory polyps and LMM might be Helicobacter Pylori infection-associated.
Muscle mass, which could be easily quantitatively detected by BIA or dual X-ray absorptiometry (DXA), is cost-effective and of great importance for the diagnosis of sarcopenia (14). It was necessary to detect the muscle mass before gastrointestinal endoscopies, which is predictive for hyperplastic and inflammatory polyps. In addition, enhanced physical exercise might be a preventive action to avoid possible gastric polyps to some extent. However, further prospective studies are required to determine the effect of physical activity on risk of gastric polyps.

STUDY STRENGTHS AND LIMITATIONS
It was cross-sectional study with large sample size, and there was a new-found association between low muscle mass and hyperplastic or inflammatory polyps. Detection of muscle mass prior to gastrointestinal endoscopies could help doctors with psychological preparation for corresponding removal of polyps.
Yet, there were some limitations to our study: (1) crosssectional nature of the research, which could not prove causality; (2) a single-center analysis with ineluctable selective bias; (3) a lack of data of muscle strengthening, which caused failure to diagnosis individuals with sarcopenia; and (4) a lack of data on physical activity/exercise, which mediated the process of low muscle mass and gastric polyps to some extent.

CONCLUSION
In general, low muscle mass was a potential indicator for predicting occurrence of hyperplastic or inflammatory polyps, rather than fundic gland polyps. The ASM/BMI was negatively correlated with the occurrence of hyperplastic or inflammatory polyps.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.