KR20230172391A - A Composition for increasing HDL cholesterol containing Helicobacter pylori disinfectant - Google Patents

Abstract

The present invention relates to the Helicobacter pylori eradication effect, and the eradication effect can increase the BMI and HDL levels of a subject, particularly increasing HDL levels in women and BMI levels in men. In addition, due to the above effects, Helicobacter pylori eradication agents can be applied to prevent, improve, or treat metabolic syndrome.

Description

Composition for increasing HDL cholesterol containing Helicobacter pylori disinfectant {A Composition for increasing HDL cholesterol containing Helicobacter pylori disinfectant}

Described herein is the eradication effect of Helicobacter pylori (HP). More specifically, it concerns the long-term effects of Helicobacter pylori eradication on metabolic parameters depending on gender.

Helicobacter pylori (HP) is a Gram-negative bacterium that infects the human gastric epithelium and is one of the most common chronic bacterial infections with a prevalence of more than 50% worldwide. Helicobacter pylori is a type I carcinogen that causes chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-related lymphoid tissue lymphoma. In addition to gastrointestinal diseases, Helicobacter pylori has been reported to be associated with many extra-gastric conditions, such as endocrine, cardiovascular, hematological, neurological, and autoimmune diseases.

Metabolic syndrome (MS) is a group of metabolic disorders including hypertension, hyperglycemia, dyslipidemia, and abdominal obesity that have been reported to increase the risk of cardiovascular or cerebrovascular disease, and have gained prominence for decades.

In recent years, positive associations between metabolic syndrome and Helicobacter pylori have been reported worldwide. However, Helicobacter pylori eradication for metabolic syndrome remains controversial despite many new studies. Several studies have reported that Helicobacter pylori eradication reduces the risk of dyslipidemia or improves metabolic syndrome, but other studies have reported conflicting results. Additionally, a recent study conducted in Taiwan showed that eradication of Helicobacter pylori reduced insulin resistance, triglycerides (TG) and low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL), thereby improving metabolism. Although parameters showed improvement, there was no significant difference in the prevalence of metabolic syndrome after H. pylori eradication. The effectiveness of Helicobacter pylori eradication for metabolic syndrome may vary depending on gender, ethnicity, diet, exercise body mass index (BMI), or long-term follow-up.

Accordingly, the present inventors studied the effect of Helicobacter pylori eradication on metabolic syndrome and the long-term effects of the eradication. As a result, Helicobacter pylori eradication increased BMI and HDL levels and showed the greatest effect in the first year, and in women After eradication, HDL increased and LDL decreased, while men's BMI increased significantly, confirming that there was a gender difference in the HP eradication effect, thus completing the present invention.

In one aspect, an object of the present invention is to provide a composition for increasing high-density lipoprotein (HDL) cholesterol containing a Helicobacter pylori eradication agent.

In another aspect, an object of the present invention is to provide a composition for increasing exercise body mass index (BMI) containing a Helicobacter pylori eradication agent.

In another aspect, an object of the present invention is to provide a composition for preventing or treating metabolic syndrome containing a Helicobacter pylori disinfectant.

In order to achieve the above object, the present invention in one aspect provides a composition for increasing high-density lipoprotein (HDL) cholesterol containing a Helicobacter pylori eradication agent.

In one exemplary embodiment, the composition can be administered to a subject infected with Helicobacter pylori.

In one exemplary embodiment, the subject may be characterized as being female.

In an exemplary embodiment, the Helicobacter pylori eradication agent is esomeprazole, amoxicillin, clarithromycin, metronidazole, tripotassium dicitrate bismuthate, tetra It may include one or more selected from the group consisting of tetracycline and moxifloxacin.

In an exemplary embodiment, the Helicobacter pylori eradication agent may be administered at a dosage of 2000 to 5000 mg/day.

In another aspect, the present invention provides a composition for increasing exercise body mass index (BMI) comprising a Helicobacter pylori eradication agent.

In one exemplary embodiment, the composition can be administered to a subject infected with Helicobacter pylori.

In one exemplary embodiment, the subject may be characterized as male.

In an exemplary embodiment, the Helicobacter pylori eradication agent is esomeprazole, amoxicillin, clarithromycin, metronidazole, tripotassium dicitrate bismuthate, tetra It may include one or more selected from the group consisting of tetracycline and moxifloxacin.

In an exemplary embodiment, the Helicobacter pylori eradication agent may be administered at a dosage of 2000 to 5000 mg/day.

In another aspect, the composition of the present invention may be a composition for preventing or treating metabolic syndrome (MS).

In one exemplary embodiment, the composition may be a pharmaceutical composition or a health functional food composition.

In an exemplary embodiment, the metabolic syndrome may include one or more selected from the group consisting of diabetes, multiple sclerosis, hypercholesterolemia, arteriosclerosis, and cardiovascular disease.

Through Helicobacter pylori eradication, BMI and HDL levels can be increased. In particular, HDL levels can be increased in women and BMI levels in men, and Helicobacter pylori eradication agents can be used to prevent, improve, or treat metabolic syndrome. there is.

Figure 1 relates to a schematic diagram of this experiment.
Figure 2 shows changes in metabolic parameters over time in patients in the HP-uninfected group, HP-non-eradicated group, and HP-erased group. Specifically, TC (A), HDL (B), and LDL (C ) and continuous changes in BMI (D). The overall trend in HDL levels differed slightly between the three groups over the 5-year follow-up period, with the differences being greatest at 1 year (B). There was a significant difference in the overall trend of BMI between groups, and the difference was also greatest at 1 year (D). There were no significant differences in TC and LDL changes over 5 years among the HP-uninfected group, HP-non-sterilized group, and HP-sterilized group (A, C).
Figure 3 relates to changes in high-density lipoprotein cholesterol (HDL) and body mass index (BMI) values over time in patients in the HP-non-infection group, HP-non-erasure group, and HP eradication group according to gender. Specifically, baseline and 2-month follow-up of HDL (A) in men, BMI (B) in men, HDL (C) in women, and BMI (D) in women in the HP-uninfected group, HP-non-eradicated group, and HP eradicated group. , represents a series of changes after 1 year, 3 years, and 5 years. The overall trends of BMI values (B) in men and HDL levels (C) in women were significantly different between the three groups. There were no significant differences in changes in HDL levels in men and BMI levels in women during the 5-year follow-up period between groups.
1 to 3, HP represents Helicobacter pylori , TC represents total cholesterol, HDL represents high-density lipoprotein cholesterol, and LDL represents low-density lipoprotein cholesterol. , BMI stands for body mass index.

Hereinafter, the present invention will be described in detail.

Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by a person skilled in the art to which the present invention pertains. In general, the nomenclature used herein is well known and commonly used in the art.

In the present invention, it was confirmed that BMI and HDL levels increased after eradication of Helicobacter pylori ( HP), and that HDL levels increased even after propensity score matching (PSM). When comparing the eradication effect between the HP-non-infection group, HP-non-sterilization group, and HP-sterilization group, significant differences were mainly observed between the HP-non-sterilization group and the HP-sterilization group. Additionally, subgroup analysis confirmed that HP eradication affects men and women differently. After eradication, HDL levels increased and LDL levels decreased in women, while BMI increased in men. The eradication effect on HDL and LDL levels in women was very significant, and the increase in BMI after eradication in men was significant after PSM.

Accordingly, in one aspect, the present invention relates to a composition for increasing high-density lipoprotein (HDL) cholesterol containing a Helicobacter pylori eradication agent.

In one exemplary embodiment, the composition can be administered to a subject infected with Helicobacter pylori.

In one exemplary embodiment, the subject may be characterized as being female.

In an exemplary embodiment, the Helicobacter pylori eradication agent is esomeprazole, amoxicillin, clarithromycin, metronidazole, tripotassium dicitrate bismuthate, tetra It may include, but is not limited to, one or more selected from the group consisting of tetracycline and moxifloxacin.

In an exemplary embodiment, the Helicobacter pylori eradication agent is administered in an amount of 2000 mg/day or more, 2100 mg/day or more, 2200 mg/day or more, 2300 mg/day or more, 2300 mg/day or more, 2400 mg/day or more, 2500 mg/day or more. more than 2600 mg/day, more than 2700 mg/day, more than 2800 mg/day, more than 2900 mg/day, more than 3000 mg/day and less than 5000 mg/day, less than 4900 mg/day, less than 4800 mg/day or less, 4700 mg/day or less, 4600 mg/day or less, 4500 mg/day or less, 4400 mg/day or less, 4300 mg/day or less, 4200 mg/day or less, 4100 mg/day or less, 4000 mg/day or less It may be administered in any dosage, but is not limited thereto.

From another aspect, the present invention relates to a composition for increasing exercise body mass index (BMI) containing a Helicobacter pylori disinfectant.

In one exemplary embodiment, the composition can be administered to a subject infected with Helicobacter pylori.

In one exemplary embodiment, the subject may be characterized as male.

In an exemplary embodiment, the Helicobacter pylori eradication agent is esomeprazole, amoxicillin, clarithromycin, metronidazole, tripotassium dicitrate bismuthate, tetra It may include, but is not limited to, one or more selected from the group consisting of tetracycline and moxifloxacin.

In an exemplary embodiment, the Helicobacter pylori eradication agent is administered in an amount of 2000 mg/day or more, 2100 mg/day or more, 2200 mg/day or more, 2300 mg/day or more, 2300 mg/day or more, 2400 mg/day or more, 2500 mg/day or more. more than 2600 mg/day, more than 2700 mg/day, more than 2800 mg/day, more than 2900 mg/day, more than 3000 mg/day and less than 5000 mg/day, less than 4900 mg/day, less than 4800 mg/day or less, 4700 mg/day or less, 4600 mg/day or less, 4500 mg/day or less, 4400 mg/day or less, 4300 mg/day or less, 4200 mg/day or less, 4100 mg/day or less, 4000 mg/day or less It may be administered in any dosage, but is not limited thereto.

From another aspect of the present invention, the composition may be a composition for preventing or treating metabolic syndrome (MS).

In an exemplary embodiment, the metabolic syndrome may include, but is not limited to, one or more selected from the group consisting of diabetes, multiple sclerosis, hypercholesterolemia, arteriosclerosis, and cardiovascular disease.

In one exemplary embodiment, the composition may be a pharmaceutical composition or a health functional food composition.

In one exemplary embodiment, the pharmaceutical composition may be provided in any formulation suitable for topical application. For example, it can be administered orally, transdermally, intravenously, intramuscularly, or by subcutaneous injection. As an example, the pharmaceutical composition may be an injection, a solution for external use on the skin, a suspension, an emulsion, a gel, a patch, or a spray, but is not limited thereto. The formulation can be easily prepared according to conventional methods in the field, and contains surfactants, excipients, wetting agents, emulsification accelerators, suspending agents, salts or buffers for adjusting osmotic pressure, colorants, flavorings, stabilizers, preservatives, preservatives or Other commonly used supplements can be used appropriately.

In a specific embodiment, the active ingredient of the pharmaceutical composition will vary depending on the subject's age, gender, weight, pathological condition and severity, route of administration, or the judgment of the prescriber. Determination of the application dosage based on these factors is within the level of the skilled artisan, the daily dosage of which is, for example, 0.1 mg/kg/day to 5000 mg/kg/day, more specifically 50 mg/kg/day to 500 mg/kg. /It may be work, but is not limited to this.

In a specific embodiment, when using the composition as an additive to a health functional food, it can be added as is or used with other foods or food ingredients, and can be used appropriately according to conventional methods. The amount of active ingredients mixed can be appropriately determined depending on each purpose of use, such as prevention, health, or treatment. The formulation of health functional foods can be in the form of powders, granules, pills, tablets, capsules, as well as general foods or beverages.

In a specific embodiment, there is no particular limitation on the type of health functional food, and examples of foods to which the composition can be added include meat, confectionery, noodles, gum, dairy products including ice cream, various soups, beverages, It includes tea, drinks, alcoholic beverages, and vitamin complexes, and can include all foods in the conventional sense.

In a specific embodiment, when manufacturing the health functional food or beverage, the composition may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range.

In a specific embodiment, beverages among the health functional foods may contain various flavoring agents or natural carbohydrates as additional ingredients like regular beverages. The above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used. The ratio of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 mL of the beverage according to the present invention, but is not limited thereto.

In a specific embodiment, in addition to the above, the health functional food according to the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, and pH adjusters. , stabilizers, preservatives, glycerin, alcohol, and carbonating agents used in carbonated beverages. In addition, the health functional food according to the present invention may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients can be used independently or in combination. The ratio of these additives is not limited, but is generally selected in the range of 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food according to the present invention.

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. However, the examples below are provided only for illustrative purposes to aid understanding of the present invention, and the scope and scope of the present invention are not limited thereto.

Materials and Methods

(Example 1-1) Research group

This study was a prospective observational cohort study. After strictly excluding all types of malignant tumors, a total of 2,267 patients who underwent esophago-gastro-duodenal endoscopy at Seoul National University Bundang Hospital from May 2003 to May 2019 were included. Most patients complained of mild indigestion symptoms or underwent endoscopy to check for the possibility of gastric adenoma or gastric cancer. Subjects were excluded from this study according to the following criteria. (1) Previous HP eradication history; (2) unknown previous eradication history; (3) unknown HP status; (4) anti-HP Ig positive without current HP infection; and (5) unknown HP post-treatment status. Additionally, patients with a history of gastric surgery and/or other major diseases, including gastric cancer, esophageal cancer, type 1 diabetes, systemic inflammation, or advanced malignant disease, were excluded. Finally, 1,521 eligible patients were analyzed, including 509 HP-negative patients and 1,012 HP-positive patients. Among HP-positive patients, 666 received successful eradication treatment, and 346 did not receive eradication treatment or failed due to patient preference, side effects, non-compliance, or antibiotic resistance (Figure 1).

(Example 1-2) Anthropometric measurements and data collection

When registering subjects in Example 1-1, total cholesterol (TC), HDL cholesterol, LDL cholesterol, TG, fasting plasma glucose (FPG), systolic blood pressure (SBP), and diastolic blood pressure ( Basic demographic data such as diastolic blood pressure (DBP) and BMI were recorded. Then, each parameter was tracked after 2 months, 1 year, 3 years, and 5 years.

(Example 1-3) Behavioral factors and past medical history

When registering subjects in Example 1-1, past medical history and behavioral factors such as smoking and drinking habits were based on questionnaires filled out by the subject patients and were also collected from medical records. Eligible patients were diagnosed with hypertension if their blood pressure was >140/90 mmHg before treatment or if they were receiving antihypertensive treatment. Diabetes is diagnosed by FPG (>126 mg/dL), 2-hour oral glucose tolerance test (>200 mg/dL), symptomatic random blood sugar test (>200 mg/dL), or glycosylated hemoglobin level (hemoglobin A1C, 6.5% or more) or diabetes treatment. Dyslipidemia was defined as increased TC (>240 mg/dL), LDL (>160 mg/dL) or TG (>200 mg/dL), or low HDL levels (<40 mg/dL).

(Example 1-4) Confirmation of HP infection

HP infection was diagnosed by esophagogastroscopy with histology, culture, or biopsy for Campylobacter-like organisms. The mid antrum and mid corpus were mucosal biopsy sites, and biopsies were performed by a single endoscopist (N.K.) for consistency.

(Example 1-5) HP eradication therapy and follow-up measures

Current HP infection was defined as a positive result in any one of three tests (histology, culture, and rapid urease test). Patients seeking eradication treatment received first-line triple therapy before 2012 and sequential treatment for 10 days thereafter. The triple therapy regimen consisted of 40 mg of esomeprazole twice daily (b.i.d), 1,000 mg of amoxicillin b.i.d., and 500 mg clarithromycin b.i.d. for 7 days. The 10-day sequential treatment was a combination of 40 mg of esomeprazole, amoxicillin 1,000 mg b.i.d. for 5 days, followed by 40 mg of esomeprazole b.i.d., 500 mg clarithromycin b.i.d., and 500 mg metronidazole twice daily for 5 days. A 13C-urea breath test was performed 4 to 6 weeks after completion of eradication treatment to evaluate the results. In patients who failed treatment after first-line therapy, 40 mg of esomeprazole b.i.d., 300 mg of tripotassium dicitrate bismutate (Denol; Green cross Co., Seoul, Korea) four times daily (q.i.d), 500 mg of metronidazole three times daily, and 500 mg of metronidazole three times daily. Prescribe 14-day quadruple therapy containing tetracycline q.i.d. or 400 mg of moxifloxacin (Avelox; Bayer Health Care, AG, Wuppertal, Germany) q.i.d., 40 mg of esomepra zole b.i.d., and 1,000 mg of amoxicillin b.i.d. A 14-day moxifloxacin-based triple therapy was prescribed. HP status was assessed by histology and/or examination for Campylobacter -like organisms at each follow-up visit for endoscopic surveillance.

(Example 1-6) Statistical analysis

Continuous data were expressed as mean ± standard deviation, and categorical data were expressed as numbers and percentages. Baseline characteristics and metabolic parameters were compared between groups using Student t-test and analysis of variance for continuous variables and chi-square test for categorical variables. A linear mixed model (LMM) was applied to compare changes in metabolic parameters over time among the HP-negative group, HP-non-sterilizing group, and HP-bacterial group. To minimize the influence of potential confounding variables affecting metabolic parameters, 1:1 propensity score matching (PSM) was used. Statistical significance was set at p<0.05. All statistical analyzes were performed using IBM SPSS Statistics version 25.0 software (IBM Corp., Armonk, NY, USA) and in collaboration with the Medical Research Collaborating Center.

(Example 1-7) Ethics declaration

All eligible patients provided written informed consent in accordance with the ethical principles of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB number: B-1904/532-110).

Basic characterization

The basic characteristics of the target patients are listed in Table 1. Of the 1,521 people finally analyzed, 509 (33.5%) were HP-negative and 1,012 (66.5%) were HP-positive. The average age was 55.6 years, and 759 patients (49.9%) were male. The proportion of men in the positive group was significantly higher than the negative group (53.2% vs 43.4%, p<0.001). There were no significant differences between groups in age, number of drinkers, number of smokers, number of patients with hypertension, diabetes, dyslipidemia, TC, HDL, LDL, TG, FPG, SBP, DBP, and BMI (Table 1). Additionally, there were no significant differences in baseline characteristics following HP infection between men and women (Table 2).

Differences in baseline characteristics between male and female subjects showed that the proportion of current drinkers and smokers was significantly higher in men than in women, TC, HDL, and LDL were significantly higher in women than in men, and TG, SBP, and DBP were significantly higher in men than in men. It was significantly higher than that of women (Table 2). FPG and BMI did not show significant differences according to gender, but patients with hypertension and diabetes were predominantly male, and patients with dyslipidemia were similar between men and women.

Baseline characteristics of patients according to HP status variable total number of patients
(n=1,521, 100%) HP-Voice
(n=509, 33.5%) HP-positive
(n=1,012, 66.5%) p-value Age (years) 55.6±13.8 54.8±15.5 56.0±12.8 0.127 male 759 (49.9) 221 (43.4) 538 (53.2) <0.001* Drinking (currently) 807 (53.1) 255 (50.1) 552 (54.5) 0.101 Smoking (current) 250 (16.4) 72 (14.1) 178 (17.6) 0.087 Total cholesterol, mg/dL 183.7±40.8 183.0±43.6 184.1±39.4 0.733 HDL, mg/dL 51.8±14.4 51.9±13.9 51.7±14.7 0.912 LDL, mg/dL 108.1±32.6 110.0±34.7 107.2±31.6 0.532 TG, mg/dL 134.5±82.5 141.7±95.0 130.8±75.0 0.271 FPG, mg/dL 129.2±35.0 140.0±43.5 124.7±30.2 0.123 SBP, mm Hg 122.9±13.2 123.9±14.4 122.4±12.7 0.369 DBP, mm Hg 73.3±8.8 74.2±9.1 72.9±8.7 0.212 BMI, kg/ ^m2 23.8±3.5 24.1±3.9 23.7±3.4 0.397 HTN 409 (26.8) 130 (25.5) 279 (27.5) 0.400 DM 160 (10.5) 53 (10.4) 107 (10.6) 0.923 dyslipidemia 294 (19.3) 106 (20.8) 188 (18.6) 0.295 Antihypertensive drug treatment 444 (29.2) 140 (27.5) 304 (30.0) 0.305 Antidiabetic drug treatment 156 (10.3) 52 (10.2) 104 (10.3) 0.971 Lipid-lowering drug treatment 278 (18.3) 105 (20.6) 173 (17.1) 0.092

Impact of HP infection on metabolic parameters according to baseline characteristics and gender. variable Male (n=759) Female (n=762) p-value gun
number of patients
(n=759, 100%) HP (-)
(n=221, 29.1%) HP (+)
(n=538, 70.9%) p-value gun
number of patients
(n=762, 100%) HP (-)
(n=288, 37.8%) HP (+)
(n=474, 62.2%) p-value Age (years) 56.2±14.2 56.2±16.2 56.3±13.3 0.934 54.9±13.3 53.8±14.9 55.6±12.2 0.064 0.067 Drinking 509 (67.1) 148 (67.0) 361 (67.1) 0.972 298 (39.1) 107 (37.2) 191 (40.3) 0.389 <0.001* smoking 227 (30.0) 67 (30.3) 160 (29.7) 0.875 23 (3.0) 5 (1.7) 18 (3.8) 0.107 <0.001* TC, mg/dL 176.1±39.3 175.2±41.0 176.5±38.8 0.764 193.1± 40.6 189.8±44.8 195.1±37.8 0.219 <0.001* HDL, mg/dL 48.2±13.4 47.4±11.5 48.5±14.1 0.671 55.5±14.5 55.2±14.6 55.7±14.6 0.844 <0.001* LDL, mg/dL 102.7±32.4 104.9±30.6 101.9±33.1 0.647 113.5±32.2 113.8±37.4 113.4±28.8 0.939 0.009* TG, mg/dL 143.7±86.8 149.4±96.9 141.4±82.7 0.603 125.0±76.8 136.0±93.9 117.6±62.2 0.153 0.047* FPG, mg/dL 126.0±36.1 133.7±60.0 124.5±30.7 0.578 133.8±33.5 143.1±35.5 125.3±30.3 0.190 0.396 SBP, mm Hg 125.7±12.6 128.5±13.5 124.4±12.0 0.074 120.4±13.3 120.1±14.0 120.5±13.0 0.873 0.001* DBP, mm Hg 75.5±8.6 77.0±8.1 74.8±8.7 0.162 71.4±8.6 72.0±9.3 71.0±8.2 0.508 <0.001* BMI, kg/ ^m2 23.7±3.2 23.9±3.6 23.7±3.1 0.641 23.9±4.0 24.2±4.3 23.8±3.8 0.511 0.343 HTN 230 (30.3) 66 (29.9) 164 (30.5) 0.866 179 (23.5) 64 (22.2) 115 (24.3) 0.520 0.003* DM 96 (12.6) 28 (12.7) 68 (12.6) 0.991 64 (8.4) 25 (8.7) 39 (8.2) 0.827 0.007* dyslipidemia 145 (19.1) 44 (19.9) 101 (18.8) 0.718 149 (19.6) 62 (21.5) 87 (18.4) 0.284 0.824

In Tables 1 and 2, data are expressed as mean ± standard deviation or number (%), HP, Helicobacter pylori; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglyceride; FPG, fasting plasma glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; *Indicates statistical significance.

Analysis of the effects of HP infection and eradication on metabolic parameters

The number of patients followed up for 2 months, 1 year, 3 years, and 5 years was 985, 918, 827, and 637, respectively. LMM analysis confirmed that there was an interaction between time and HP status on BMI levels, which showed a significant trend in BMI levels over the 5-year follow-up period between the HP-uninfected group, HP-uninfected-infected and HP-erased groups. This indicates that there is a difference (p=0.006). HDL also showed a slightly significant difference (p=0.088), but there was no significant difference in TC, LDL, TG, FPG, SBP, and DBP between groups (Table 3).

We also compared changes in metabolic parameters from baseline to each follow-up time point between the HP-uninfected group, HP-uninfected-infected and HP-erased groups. As a result, the BMI level increased statistically significantly at 1 year after eradication (p=0.002), and the difference decreased at 3 and 5 years (p=0.088 and p=0.203, respectively). HDL increased after eradication, whereas it decreased in the HP-non-sterilization group. The difference between groups was greatest in year 1 (p=0.027) and decreased thereafter (p=0.095 in year 3, p=0.691 in year 5) (Table 4). As a result of post hoc analysis, HDL differed between the HP-non-sterilized and HP-sterilized groups (p=0.053 after Bonferroni correction), and BMI differed between the HP-non-sterilized and HP-sterilized groups (p=0.003) and the HP-non-sterilized group (p=0.003). There was a difference between the groups and the HP-erased group (p=0.041) ( Table 5 ). The values of each parameter during the 5-year follow-up period are shown in Figure 2.

Linear mixed model results for HP non-infected, HP non-sterilized, and HP eradicated groups. parameter comprehensive
effect
(p-value)* 2 months 1 year 3 years 5 years β (95% CI) Modified
p-value β (95% CI) Modified
p-value β (95% CI) Modified
p-value β (95% CI) Modified
p-value TC 0.835 -0.85 (-4.65 to 2.97) 0.661 2.50 (-1.02 to 6.06) 0.165 -1.36 (-4.59 to 1.89) 0.409 -0.52 (-3.82 to 2.82) 0.761 HDL 0.088 0.72 (-0.69 to 2.14) 0.321 1.15 (-0.09 to 2.41) 0.072 0.85 (-0.32 to 2.02) 0.158 0.78 (-0.41 to 1.98) 0.204 LDL 0.870 -7.24 (-12.41 to -2.04) 0.006 -4.32 (-8.90 to 0.22) 0.064 -3.37 (-7.56 to 0.81) 0.115 -5.49 (-9.70 to -1.25) 0.011 TG 0.480 -5.46 (-15.47 to 4.65) 0.288 -0.98 (-9.95 to 8.03) 0.832 -4.69 (-13.06 to 3.67) 0.273 -4.57 (-13.07 to 3.92) 0.293 FPG 0.209 -3.44 (-13.23 to 6.07) 0.490 -6.73 (-16.07 to 2.49) 0.162 -3.63 (-12.48 to 5.42) 0.434 -4.60 (-14.14 to 4.89) 0.352 SBP 0.926 1.67 (-0.82 to 4.15) 0.188 -0.13 (-2.11 to 1.84) 0.896 -0.97 (-2.66 to 0.71) 0.261 0.93 (-0.78 to 2.63) 0.285 DBP 0.297 1.33 (-0.26 to 2.92) 0.101 0.43 (-0.84 to 1.69) 0.510 0.55 (-0.53 to 1.62) 0.318 0.82 (-0.27 to 1.91) 0.139 BMI 0.006?? -0.41 (-0.90 to 0.08) 0.102 -0.44 (-0.90 to 0.03) 0.069 -0.37 (-0.76 to 0.02) 0.067 -0.70 (-1.11 to -0.29) 0.001??

Table 3 shows the effects of HP infection and HP eradication on metabolic parameters. In Table 3, HP, Helicobacter pylori; , estimate; CI, confidence interval; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglyceride; FPG, fasting plasma glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; *Significance of differences in metabolic parameters over time between HP infected, HP non-eradicated, and HP eradicated groups; ?? Indicates statistical significance.

In Table 4, data are presented as mean ± SD, and *p < 0.05 is considered significant. In Table 4, HP, Helicobacter pylori; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglyceride; FPG, fasting plasma glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, represents body mass index.

In Table 5, HDL, high-density lipoprotein cholesterol; BMI, body mass index; HP, Helicobacter pylori; *Indicates statistical significance.

Analysis of the effect of HP eradication on metabolic variables according to gender

In men, BMI increased after eradication, whereas it decreased in the HP-non-infected and HP-non-sterilized groups. The difference between groups was significant at 1 year (p=0.010), but not significant at 3- and 5-year follow-up (p=0.156 at 3 years, p=0.243 at 5 years). Post hoc analysis showed that the differences in BMI among men were significant between the HP-eradicated and HP-uninfected groups and between the HP-erased and HP-uninfected groups (Table 6). Other metabolic parameters, including HDL, showed no significant differences between groups at each time point (Table 7).

For women, unlike men, there was no significant difference in BMI change among the three groups from baseline to each time point. Instead, HDL showed significant differences between groups. HDL levels increased after eradication, whereas they decreased in the non-sterilization group. The difference in HDL change was greatest at 1 year (p=0.023) and gradually decreased thereafter (p=0.090 at 3 years, p=0.116 at 5 years). LDL decreased after eradication, and the difference between groups was significant at 3-year follow-up (p=0.038) (Table 7). Post hoc analysis showed that the difference in HDL and LDL changes in women was significant between the HP-non-erased and HP-erased groups (Table 6). Changes in HDL and BMI over 5 years in male and female subjects are shown in Figure 3.

In Table 6, HDL, high-density lipoprotein cholesterol; BMI, body mass index; HP, Helicobacter pylor, * Indicates statistical significance.

In Table 7, data are presented as mean ± SD. HP, Helicobacter pylori; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; BMI, represents body mass index. *p-value was obtained through analysis of variance, and p<0.05 is considered significant.

Analysis of the effect of HP eradication on metabolic parameters after PSM

After 1:1 PSM, the number of patients in the HP-non-sterilization group and the HP-sterilization group was 346. All standard mean differences for each variable were less than 0.2, and the baseline characteristics of eligible patients before and after PSM are shown in Table 8. LMM analysis after PSM indicates that there is an interaction between time and HP-erasing treatment on HDL levels (p=0.048). Levels of TC, LDL, TG, FPG, SBP, DBP and BMI showed no interaction between time and HP-eradicate treatment (Table 9).

As a result of comparing metabolic variables at each time point, HDL increased after HP-erasure, whereas it decreased in the non-sterilization group. The difference between groups was significant at 1 year (p=0.025) (Table 10). In subgroup analysis, for women, the difference in HDL between groups remained significant even after PSM (p=0.006 at 1 year, p=0.031 at 3 years, and p=0.014 at 5 years). The difference in BMI among male subjects after PSM was marginally significant (p=0.089 at 1 year, p=0.123 at 3 years, and p=0.643 at 5 years). For women, the difference in LDL between groups remained significant after PSM at 3 years (p=0.038) (Table 11).

In Table 8, data are expressed as mean ± standard deviation or number (%). HP, Helicobacter pylori; PSM, propensity score matching; SMD, standardized mean difference; HTN, hypertension; DM, diabetes mellitus

Table 9 describes the effect of HP eradication treatment on metabolic parameters over time compared to baseline. In Supplementary Table 4 , estimate; CI, confidence interval; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglyceride; FPG, fasting plasma glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; *Significance of differences in metabolic parameters over time depending on whether or not eradication treatment is received; † Indicates statistical significance.

In Table 10, data are expressed as mean ± standard deviation or number (%), and *p < 0.05 is considered significant. In Supplementary Table 5, TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglyceride; FPG, fasting plasma glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, represents body mass index.

In Table 11, data are presented as mean ± SD. HP, Helicobacter pylori; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; BMI, represents body mass index. *p-value was obtained through analysis of variance, Bonferroni correction coefficient was 4, and adjusted p<0.05 was considered significant.

Claims (9)

A composition for increasing high-density lipoprotein (HDL) cholesterol and/or exercise body mass index (BMI) comprising a Helicobacter pylori eradication agent.
According to paragraph 1,
The composition is administered to a subject infected with Helicobacter pylori.
According to paragraph 2,
The composition is for increasing high-density lipoprotein (HDL) cholesterol, and the subject is a woman.
According to paragraph 2,
The composition is for increasing exercise body mass index (BMI), and the subject is a male.
According to paragraph 1,
The Helicobacter pylori eradication agents include esomeprazole, amoxicillin, clarithromycin, metronidazole, tripotassium dicitrate bismuthate, tetracycline, and moxifloc. A composition comprising at least one selected from the group consisting of moxifloxacin.
According to paragraph 1,
A composition wherein the Helicobacter pylori eradication agent is administered at a dosage of 2000 to 5000 mg/day.
According to any one of claims 1 to 6,
The composition is for preventing or treating metabolic syndrome.
In clause 7,
The composition is a pharmaceutical composition or a health functional food composition.
In clause 7,
The composition, wherein the metabolic syndrome includes one or more selected from the group consisting of multiple sclerosis, hyperlipidemia, hypercholesterolemia, arteriosclerosis, and cardiovascular disease.