Huda S.H. Al-Khalidy1, Riyadh Mohamad Hasan2, Laith Hikmet Muhsun3Batool Mutar Mahdi4* and Raghad Kassem Mohammed5

1Department of clinical Biochemistry, Al-Kindy College of Medicine, University of Baghdad, Iraq.
2Department of Surgery, Al-Kindy College of Medicine, University of Baghdad, Iraq.
3CABM, FICMS, Al-Kindy Teaching Hospital, Iraq.
4Consultant Clinical Immunology, Head of HLA Research Unit, Department of Microbiology, Al-Kindy College of Medicine, Baghdad University, Iraq.
5BSc Chemical Science, Iraq.

Abstract

Endoscopic gastritis is a term used when there is an inflammatory change in the gastric mucosa like color and/or structure that was noticed by endoscope. Is to assesses the effect of these factors and association of adiponectin with these factors. This is a case-controlled study. The study consists from 100 subjects. Eighty of them had gastritis by endoscopy Forty of them were H. pylori positive and the rest were H. pylori negative. The rest twenty persons were healthy control group. Demographic information’s were taken like age, sex and others by questionnaire. Endoscopy and lipid profile were done for them. Adiponectin was significantly lower ( P=0.001) in gastritis patients whether infected (8.783±0.968) with H pylori or not (8.278   ±0.838) when compared with control group (9.119±0.1593)  (Table-1-). Regarding lipid profile , there was a significant in all parameters of lipid profile in gastritis patients than healthy group (Table-1-). Analysis of correlation between adiponectin and BMI and weight demonstrated a negative correlation with gastritis with h pylori infection (r= -0.068 and r=0.356 respectively). This study shows that adiponectin had an important role in gastritis especially when there is an h pylori infection. Its level had a negative correlation with BMI and lipid profile.

Keywords: Adiponectin, gastritis, h pylori.

Introduction

Endoscopic gastritis is a term used when there is an inflammatory change in the gastric mucosa like color and/or structure that was noticed by endoscope1,2. This can be defined by flat depressed white spot surrounded by reddish area with superficial bleeding or small elevated area with umblication in the center3. There are many factors effect upper gastrointestinal diseases like gastritis, gastric ulcer, deoudenitis and gastroesophageal reflux disease. One of these important factors is body mass index (BMI) which is known to be associated with gastritis4. There are several studies showed the association and potential effect of obesity on gastritis5,6. Yamamoto et al. showed that BMI was significantly higher and the serum adiponectin level was significantly lower in gastritis-positive patients than in gastritis-negative patients7. This study demonstrated the association between hypoadiponectinemia and erosive gastritis,  adding to that  other studies  showed that low plasma adiponectin levels had a role in gastric cancer8,9. So adipose tissue is an important endocrine organ secreting a large number of endocrine factors like adiponectin that had wide physiological functions10. Increase in its serum level protect against many diseases11. Other factor that leads to gastritis is infection with Helicobacter pylori that involves in progression to atrophy , intestinal  metaplasia and gastric cancer12. After the discovery of H. pylori in 1983, these bacteria is an important factor in gastritis and its prevalence was decreased in Western countries and in some Asian countries like Japan13. It found that treatment and eradication of these bacteria leads to increased circulating adiponectin levels in Japanese patients and could be helpful for preventing gastritis and its progression to other diseases 14.

Consequently, there are several important factors that related with endoscopic gastritis like BMI, Helicobacter pylori, lipid profile and adiponectin. This study assesses the effect of these factors and association of adiponectin with these factors.

Patients and methods
This is a case-controlled study done by Al-Kindy College of Medicine from January 2017 to June 2018. The approval of medicinal morals board was obtained for contributors in this study. The proposal was accepted by the Al-Kindy College of Medicine and Al-Kindy Teaching Hospital. The knowledgeable permission was obtained from all of them. The Scientific and Ethical Committee of Al-kindy medical college and Al-Kindy Teaching Hospital had approved and registered the study.  Written informed consents were obtained from the patients and control normal blood donors.

The inclusion criteria were patients complaining from dyspepsia, upper abdominal pain, acid regurgitation, heartburn The exclusion criteria were patients who had history of gastric surgery, peptic ulcer, gastric cancer, previous H. pylori eradication, esophageal avarices and patients who were on medications like antacids, H2 blockers, proton pump inhibitors and non-steroidal anti-inflammatory drugs.

Data were collected from 100 subjects. Eighty of them had gastritis by endoscopy Forty of them were H. pylori positive and the rest were H. pylori negative. The rest twenty persons were healthy control group. Demographic information’s were taken like age, sex and others by questionnaire.

Endoscopy
All patients examined for upper gastrointestinal endoscopic using gastroscope: GIF-H260; Olympus, Tokyo, Japan and Display screen; Olympus OEV-261H liquid crystal display monitor; Olympus, Tokyo, Japan. Endoscopic examinations performed by well-trained gastroenterologists. The presence or absence of endoscopic gastritis was determined by endoscopist according to their criteria15.

Anthropometric Measurements
All measurement like weight, height, waist circumference, body mass index was calculated as weight in kilograms divided by the square of height in meters (16):

  1. Normal Weight group: BMI 18.5 – 24.9 kg/m2.
  2. Over Weight group: BMIs 25.0 – 29.9 kg/m2.
  3. Obese group : BMIs e” 30 kg/m2.
    Waist circumference was measured in centimeters (cm)17.

Biochemical analysis
Five ml of venous blood were obtained from all subjects. Serum were analysis for lipid profile (cholesterol, triglyceride, HDLP, LDLP (Human-Germany), adiponectin (Human-Germany), and H pylori (Eco test-Chain).

Statistical analysis
Was done using MiniTab version 3.0 software. Data analysis was done using chi- square test for frequencies, while ANOVA test for means and standard deviation.  Correlation coefficient used to assess the correlation between different parameters by Pearson correlation. P-value less than 0.05 were considered statistically significant.

Results and Discussion

The total numbers of study groups were one hundred subjects, forty of them were gastritis with H pylori infection and the other group was gastritis alone without H pylori infection and the rest were twenty control healthy subjects. There was no significant differences among their ages and gender (P=0.134 and P= 0.334 respectively)(table-1-).There was a significant increase in BMI(P=0.000), weight(P=0.000), waist circumference (P=0.018) in patients with gastritis with or without H pylori when compared with control group(Table-1).

Table 1. Demographic differences of various parameters among patients with gastritis with and without H pylori infection and control group

P- value Control
Group
No.=20
X±SD
Gastritis patients with H pylori 
-ve
NO.=40
X±SD
Gastritis patients with H pylori
+ve
NO.=40
X±SD
Parameters
0.134

 

37.30± 12.43
(25-68)
46.25 ±21.07
(14-83)
40.70±  14.95
(12-68)
Age (year)
Range
0.334 14(70%) 20(50%) 22(55%) Male %
06(30%) 20(50%) 18(45%) Female  %
0.024 1.7230± 0.0814 1.6905± 0.1297 1.6460±0.0898 Height (m)
0.000 73.72±  2.54 78.39± 3.42 82.23 ± 3.79 Weight (Kg)
0.000 24.408± 0.777 27.30± 1.05  27.134 ±0.853 BMI KG/m2
0.018 93.45± 13.30 95.80± 15.41 103.90±   16.14 Waist circumference
Cm
0.994 1.0340± 2.15 1.0985± 3.46  1.1140 ± 2.36 Waist to Hip Ratio
0.001 9.119±0.1593 8.278   ±0.838 8.783±0.968 Adiponectin
ng/ml
0.000 200.7±  35.9 253.6±16.6 285.3±  14.8 Cholesterol
Mg/dl
0.000 160.0 ±  30.2 290.0 ± 36.4 174.5±  17.9 Triglyceride
Mg/dl
0.000 40.92  ±1.20 48.60± 3.39 52.48 ± 3.41 HDL
Mg/dl
0.001 164.2 ±  27.7 175.1± 15.7 179.2± 13.4 LDL
Mg/dl
0.000 3.545±0.0385 4.338±0.0734 6.70±  0.197 LDL/H|DL

In this study, adiponectin was significantly lower ( P=0.001) in gastritis patients whether infected (8.783±0.968) with H pylori or not (8.278   ±0.838) when compared with control group (9.119±0.1593)  (Table-1-). Regarding lipid profile , there was a significant in all parameters of lipid profile in gastritis patients than healthy group (Table-1-). Analysis of correlation between adiponectin and BMI and weight demonstrated a negative correlation with gastritis with h pylori infection (r= -0.068 and r=0.356 respectively) while in gastritis without h pylori infection only negative correlation with weight, waist circumference and waist hip ratio (Table-2-). About lipid profile with adiponectin, there was a negative correlation between adiponectin and cholesterol, Triglyceride, LDL. There is only positive correlation between adiponctin and HDL and LDL/HDL in both groups of gastritis whether infected with H pylori or not as showed in table-2.

Table 2. Pearson correlation analysis of adiponectin with different parameters in GERD patients

P- value Gastritis patients with H pylori 
-ve
NO.=40r
P- value Gastritis patients with H pylori +ve
NO.=40r
Parameters
0.266 -0.180 0.266 -0.180 Age (year)
0.527 0.103 0.000 -0.601 Height (Cm)
0.007 -0.418 0.024 -0.356 Weight (Kg)
0.184 0.214 0.677 -0.068 BMI KG/m2
0.001 -0.506 0.429 -0.129 Waist (Cm)
0.103 -0.262 0.927 0.015 Hip Waist Ratio
0.013 -0.391 0.791 -0.043 Cholesterol  Mg/dl
0.337 -0.156 0.030 -0.344 Triglyceride Mg/dl
0.809 0.040 0.001 0.487 HDL Mg/dl
0.047 -0.315 0.735 -0.055 LDL Mg/dl
0.184 0.214 0.308 0.165 LDL/HDL

It has been reported that obesity and increased BMI are related to gastrointestinal symptoms and endoscopic gastritis. Adiponectin is an anti-inflammatory and its serum concentrations are reduced in obesity with increased visceral fat accumulation. In this study, gastritis developed when there is increased in BMI especially with H pylori infection. This is associated with decreased adiponctin serum level. This is in agreement with other results that showed adiponectin promotes ulcer healing, decrease ulcer area, reduce edema and leukocytes infiltration in submucosal layer18,19. It is well known that adiponectin is associated with better inflammation reduction and healing20. The gastric protective effect of adiponectin might be due to reduction of neutrophil infiltration, decrease in gastric motility and relaxation of circular muscles, flattening of the folds and reduce the volume of the gastric irritants on the rugal crest21,22. In addition to that, adiponectin activates AMP-activated protein kinase (AMPK) system that regulates growth arrest and apoptosis by stimulating p53 and p21 and decreases production of reactive oxygen species (ROS) which may result in decreased activation of mitogen-activated-protein-kinase (MAPK)23,24,25. So increase level of adiponectin reduce the risk of development of many diseases26. There is a negative correlation with body mass index and adeponectin in gastritis with H pylori and in general there is in agreement with other studies that demonstrated plasma adiponectin concentrations are inversely related to BMI, weight and waist circumference27. The possible mechanism is that during adipogenesis, a feedback inhibition in its production may occur due to increase in the production of other adipocytokines like TNF-± that decrease adipocyte expression and secretion of adiponectin28. In addition to that infection with H pylori leads to decrease in adiponectin serum level which in agreement with other studies 12,29. This study demonstrated a negative correlation between adiponectin with Cholesterol, triglyceride and LDL. Adiponectin has been shown to regulate weight reduction as well as free fatty acid oxidation. The mechanism underlying this is regulation of production proteins associated with triglyceride metabolism including acyl CoA oxidase, activated protein kinase, and peroxisome proliferator- activated receptor ³ (PPAR³) which is in agreement with other studies30.

Conclusions

This study shows that adiponectin had an important role in gastritis especially when there is an h pylori infection. Its level had a negative correlation with BMI and lipid profile.

References

  1. Genta RM. Review article: gastric atrophy and atrophic gastritis—nebulous concepts in search of a definition. Aliment PharmacolTher. 1998; 12:17–23.
  2. Lee S. Endoscopic Gastritis: What Does It Mean? Dig Dis Sci 2011; 56: 2209–2211.
  3. Ahn SY, Lee SY, Hong SN, et al. Endoscopic diagnosis of opentype atrophic gastritis is related to the histological diagnosis of intestinal metaplasia and Cdx2 expression. Dig Dis Sci. 2011; 56: 1119–1126.
  4. Kim HJ, Yoo TW, Park DI, Park JH, Cho YK, Sohn CI, Jeon WK, Kim BI: Influence of overweight and obesity on upper endoscopic findings. J Gastroenterol Hepatol 2007; 22: 477–481.
  5. Csendes A, Burgos AM, Smok G, Beltran M: Endoscopic and histologic findings of the foregut in 426 patients with morbid obesity. Obes Surg 2007; 17: 28–34.
  6. Yamamoto S, Watabe K, Takehara T. Is obesity a new risk factor for gastritis? Digestion. 2012; 85:108-10.
  7. Yamamoto S, Watabe K, Tsutsui S, et al. Lower serum level of adiponectin is associated with increased risk of endoscopic erosive gastritis. Dig Dis Sci. 2011; 56: 2209-2211.
  8. Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005; 11: 466–472.
  9. Fang H, Judd RL. Adiponectin Regulation and Function. Compr Physiol. 2018; 8:1031-1063.
  10. Kashiwagi R, Yamada Y, Ito Y, Mitsui Y, Sakaue T, Iwamoto R, Saisho K, Tamba S, Yamamoto K, Watanabe T, Fujimoto T, Iwahashi H, Matsuzawa Y. Increase in Adiponectin Level Prevents the Development of Type 2 Diabetes in Japanese Men With Low Adiponectin Levels. J Endocr Soc. 2018; 14: 753-764.
  11. Duval F, Dos Santos E, Maury B, Serazin V, Fathallah K, Vialard F, Dieudonné MN. Adiponectin regulates glycogen metabolism at the human fetal-maternal interface. J Mol Endocrinol. 2018: pii: JME-18-0013.
  12. Chen MJ, Wang TE, Chang WH, Liao TC, Lin CC, Shih SC. Nodular gastritis: an endoscopic indicator of Helicobacter pylori infection. Dig Dis Sci. 2007; 52: 2662–2666.
  13. Rothenbacher D, Brenner H: Burden of Helicobacter pylori and H. pylori -related diseases in developed countries: recent developments and future implications. Microbes Infect. 2003; 5: 693–703.
  14. Ando T, Ishikawa T, Takagi T, Imamoto E, Kishimoto E, Okajima A, Uchiyama K, Handa O, Yagi N, Kokura S, Naito Y, Mizuno S, Asakawa A, Inui A, Yoshikawa T. Impact of Helicobacter pylori eradication on circulating adiponectin in humans. Helicobacter. 2013; 18:158-64.
  15. Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis. The updated Sydney System. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol. 1996; 20:1161–1181.
  16. Suman S Dambal, Suchetha Kumari N. Evaluation of lipid peroxidation and total antioxidant status in human obesity; International Journal of Institutional Pharmacy and Life Sciences 2012; 2: 2249-6807.
  17. WHO . Steps Manual. Part 3 Training and Practical Guides. Geneva: WHO 2008.
  18. Dutta SK, Arora M, Kireet A, Bashandy H, Gandsas A: Upper gastrointestinal symptoms and associated disorders in morbidly obese patients: a prospective study. Dig Dis Sci, 2009; 54: 1243–1246.
  19. Fard AA, Hajrezaie  M,  Kadir FA,  Sefideh FA, Salama SM,  Al-Najar ZA. The Effects of Combined Adiponectin-Metformin on Glucose and Lipids Levels in Mice and Acute Toxicity and Anti-Ulcerogenic Activity of Adiponectin Against Ethanol-Induced Gastric Mucosal Injuries in Rat.Molecules 2011, 16: 9534-9552.
  20. Schulze, M.B.; Rimm, E.B.; Shai, I.; Rifai, N.; Hu, F.B. Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care 2004, 27: 1680-1687.
  21. Abdulla, M.A.; Ahmed, K.A.A.; Al-Bayaty, F.H.; Masood, Y. Gastroprotective effect of Phyllanthus niruri leaf extract against ethanol-induced gastric mucosal injury in rats. Afr. J.Pharm. Pharacol. 2010, 4: 226-230.
  22. Indran, M.; Mahmood A.A.; Kuppusamy, U.R. Protective effect of Carica papaya L. leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats. West Indian Med. J. 2008, 57: 323-326.
  23. Igata M, Motoshima H, Tsuruzoe K, Kojima K, Matsumura T, Kondo T,Taguchi T, Nakamaru K, Yano M, Kukidome D, Matsumoto K, Toyonaga T,Asano T, Nishikawa T, Araki E: Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res 2005: 97: 837-844.
  24. Ouedraogo R, Wu X, Xu SQ, Fuchsel L, Motoshima H, Mahadev K, Hough K,Scalia R, Goldstein BJ: Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. Diabetes 2006, 55: 1840-1846.
  25. Govindarajan B, Klafter R, Miller MS, Mansur C, Mizesko M, Bai X,LaMontagne K Jr, Arbiser JL: Reactive oxygen-induced carcinogenesis causes hypermethylation of p16(Ink4a) and activation of MAP kinase. Mol Med 2002, 8:1-8.
  26. Kashiwagi R, Yamada Y, Ito Y,  Mitsui Y,  Sakaue T,  Iwamoto R. Increase in Adiponectin Level Prevents the Development of Type 2 Diabetes in Japanese Men With Low Adiponectin Levels. Journal of the Endocrine Society. 2018; 2: 753–764.
  27. Takashi K and Toshimasa Y. ‘’ Adiponectin and Adiponectin Receptors.’’ Japan; and Core Research for Evolutional Science and Technology of Japan Science and Technology Agency. 2005; 3:32-42.
  28. Mamaghani F, Zarghami N, Maleki MJ, Pourhassan – Moghaddam M, Hossein panah F. Variation of Adiponectin Levels in Normal and Obese subjects: Possible Correlation with Lipid Profiles. International Journal of Endocrinology Metabolism 2009; 3:170-178.
  29. Polyzos SA, Kountouras J, Zavos C, Pyrrou N, Tantsi N. Helicobacter pylori infection and serum adiponectin. Helicobacter. 2013; 18:321-2.
  30. Ursula Meier and Axel M. Gressner .’’Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin.’’ Clinical Chemistry : 2009:1511–25.