Mehmet Sargyn, Oya Uygur-Bayramiçli, Haluk Sargyn, Retat Dabak, Ekrem Orbay, Dilek Yavuzer, Ali Yayla, Departments of Endocrinology and Diabetes, Gastroenterology, Family Medicine, Pathology and Internal Medicine; Kartal Education and Research Hospital, Istanbul, Turkey
Correspondence to: Oya Uygur-Bayramiçli, Altunizade mah. Atyf Bey sok. çamlyk sitesi II. Kysym A Blok No: 53/9, 81020 Usküdar/ISTANBUL, Turkey.  bayramicli@hotmail.com
Telephone: +90-216-4184063    Fax: +90-216-4188637
Received: 2002-12-05    Accepted: 2003-01-03

Abstract
AIM: To study the eradication rate of Helicobacter pylori (Hp) in a group of type 2 diabetes and compared it with an age and sex matched non-diabetic group.

METHODS: 40 diabetic patients (21 females, 19 males; 56±7 years) and 40 non-diabetic dyspeptic patients (20 females, 20 males; 54±9 years) were evaluated. Diabetic patients with dyspeptic complaints were referred for upper gastrointestinal endoscopies; 2 corpus and 2 antral gastric biopsy specimens were performed on each patient. Patients with positive Hp results on histopathological examination comprised the study group. Non-diabetic dyspeptic patients seen at the Gastroenterology Outpatient Clinic and with the same biopsy and treatment protocol formed the control group. A triple therapy with amoxycillin (1 g b.i.d), clarithromycin (500 mg b.i.d) and omeprazole (20 mg b.i.d.) was given to both groups for 10 days. Cure was defined as the absence of Hp infection assessed by corpus and antrum biopsies in control upper gastrointestinal endoscopies performed 6 weeks after completing the antimicrobial therapy.

RESULTS: The eradication rate was 50 % in the diabetic group versus 85 % in the non-diabetic control group (P<0.001).

CONCLUSION: Type 2 diabetic patients showed a significantly lower eradication rate than controls which may be due to changes in microvasculature of the stomach and to frequent antibiotic usage because of recurrent bacterial infections with the development of resistant strains.

Sargyn M, Uygur-Bayramiçli O, Sargyn H, Orbay E, Yavuzer D, Yayla A. Type 2 diabetes mellitus affects eradication rate of Helicobacter pylori. World J Gastroenterol  2003; 9(5): 1126-1128
http://www.wjgnet.com/1007-9327/9/1126.asp

INTRODUCTION
Helicobacter pylori (Hp) is the most prevalent infection all over the world and has been considered as the causative agent of many gastrointestinal diseases^[1,2]. Type 2 diabetes mellitus can present with many protean gastrointestinal symptoms and Hp can play a role in this context^[3,4].
     Although a number of studies has been performed on the association of Hp and diabetes mellitus, the results have been controversial. In a large study performed by Xia et al., the seroprevalance of Hp infection was not statistically different in patients with diabetes mellitus and non-diabetic controls^[5]. In earlier studies, the prevalence of Hp was reported to be 62 % versus 21%, but according to Xia et al., the prevalence of Hp should be corrected for age and gender and there are no differences if an adjustment has been done for these variables^[6].
     The literature is even scarce about treatment regimens of Hp infection in diabetes mellitus. We also know that the eradication of Hp shows great differences between different ethnic groups and in patients with some chronic conditions^[1,7]. Therefore we proposed that the eradication rate of Hp may be also different in type 2 diabetics in comparison to non-diabetic controls and we planned a prospective study to elucidate the eradication rate of Hp infection in type 2 diabetic subjects.

MATERIALS AND METHODS
Patients
Diabetic patients with dyspeptic complaints from Diabetes Outpatient Clinic were referred for upper gastrointestinal endoscopies in the Gastroenterology Department. Upper gastrointestinal endoscopies were performed in a standard fashion with a videoendoscope (Pentax G-2940, Japan) by the same endoscopist. Endoscopic findings were noted and Hp infection was assessed using 2 gastric antrum and 2 gastric corpus biopsy specimens, which were evaluated with the rapid urease test and the pathological examination (Haematoxylin-Eosin staining and Giemsa if the first stain was negative). Only patients with positive results for Hp in pathological specimens were included in the study. The study population consisted of 40 patients with type 2 diabetic (21 females and 19 males; mean age 56±7 years) and 40 non-diabetic dyspeptic patients as a control group from Gastroenterology Outpatient Clinic  (20  females and 20 males; mean age 54±9 years) matched for sex and age (Table 1). All patients had detailed information about the study and written informed consent.

Table 1  Characteristics of the patients in diabetic and control groups

Methods
At enrolment and at the end of the treatment, each patient completed a dyspepsia questionnaire proposed by Buckley et al., which had been slightly modified^[8]. A triple therapy with amoxycillin (1 g b.i.d), clarithromycin (500 mg b.i.d) and omeprazole (20 mg b.i.d) was given for 10 days. After 10 days, the patients received 20 mg omeprazole for 5 weeks if a gastric or duodenal ulcer was identified in the initial endoscopy or 40 mg of famotidin if there was gastritis. Cure was defined as the absence of Hp infection assessed by corpus and antrum biopsies in control upper gastrointestinal endoscopies performed 6 weeks after completing the antimicrobial therapy. Endoscopic findings were evaluated again in control endoscopy and compared with initial endoscopic findings. Any side effects due to the treatment were reported.
     During the same study period, dyspeptic patients seen at the Gastroenterology Outpatient Clinic were taken as the control group if there was no history of type 2 diabetes, and their fasting plasma glucose levels were in normal limits (between 80-110 mg/dl) and pathological Hp positivity was found  in gastric antrum and corpus specimens. The same triple therapy and a control upper gastrointestinal endoscopy after 6 weeks were also applied to the control group.

Statistical analysis
Results were expressed as means ± SEM. Statistically significant differences between groups were assessed using either Student t test, Fischer's exact test or ANOVA test, as appropriate. P<0.05 was considered to be significant.

RESULTS
All enrolled patients completed the study. Hp was eradicated in 50 % (20/40) type 2 diabetic patients and in 85 % (34/40) non-diabetic dyspeptic patients. The eradication rate was significantly lower in diabetics in comparison to the controls (P<0.05).
     There were no side effects in both groups, which led to discontinuation of the treatment.
     At baseline, type 2 diabetic patients infected with Hp showed a high prevalence of gastrointestinal symptoms. There was a statistically significant decrease in epigastric pain, nausea and belching after Hp eradication treatment (Table 2).

Table 2  Prevalence of gastrointestinal symptoms in type 2 diabetic patients before and after the treatment

Denotes: NS=not significant

      Age, duration of the diabetes and Haemoglobin A1c levels were not significantly different between the diabetics in whose Hp was eradicated and whose Hp was not eradicated (Table 3).

Table 3  Comparison of demographic data of diabetic patients in whom Hp was eradicated and Hp was not eradicated

DISCUSSION
Hp infection is responsible for up to 90 % of upper gastrointestinal diseases and is linked to the development of gastric carcinoma, MALT associated lymphoma and has to be eradicated whenever it's possible^[9,10].
      Standard triple therapy (Omeprazole, Clarithromycine and Amoxycillin) has been shown to be highly effective in the eradication of Hp in non-diabetic subjects in many previous studies (91 %)^[11,12]. In our control group, we found an eradication rate of 85 %, which was compatible with the results in the literature.
     Many authors have extensively explored the relationship between Hp and diabetes mellitus. There has been controversial results in previous studies but in a larger, well-designed study of Xia et al., there was no difference of the seroprevalence of Hp infection between patients with diabetes mellitus and non-diabetic controls^[5]. But there were no studies which explored the efficacy of anti Hp protocols in type 2 diabetics, whereas in a study of Gasbarrini et al. in type 1 diabetics, the Hp eradication rate was 65 % in comparison to 92 % in controls^[13]. In another study performed on type 1 diabetics, the eradication rate was 62 % with different triple antibiotic regimens and this could be increased by quadruple regimen to 88 %^[14]. In the present study performed on type 2 diabetics, a much lower eradication rate of Hp (50 %) was found. Histopathological examination was used in this study for the detection of pre and post treatment Hp and as the gold standard, it was more reliable and reproducible than the 13C urea breath test, which has been used in the studies by Gasbarrini et al^[13,14].
      Immunosuppression in diabetes might predispose to the low eradication rate of Hp infection but other mechanisms may also explain the low eradication rate of Hp in type 2 diabetics. Type 2 diabetics are more susceptible to many bacterial and mycotic infections, which may lead to frequent use of antibiotics, and to the development of resistance^[15-18].
     Due to absorption problems in gastric mucosa, the extent of antibiotic absorption may be less^[19]. This study showed a high rate of pathological endoscopic findings in type 2 diabetics, which may lead to disorders in gastrointestinal motility and to insufficient absorption of the drugs. Autonomic neuropathy has also been accused as a culprit. But studies in the literature suggested that there was no correlation between Hp positivity and delay in gastric emptying.
    A standard 10 days triple therapy with conventional antibiotics seems not to be warranted in diabetics. Due to problems of absorption and motility, alternative regimens with longer duration seem to be necessary for a higher eradication rate. In particular, if we take into consideration that gastrointestinal symptoms, which are quite frequent in diabetics, are significantly improving when it is possible to eradicate Hp, we should try to eradicate Hp in diabetic subjects. But this is a new area of research and the larger prospective studies with different anti Hp regimens for type 2 diabetics are needed.

ACKNOWLEDGEMENT
The authors thank endoscopy assistants Aygün Ityk, RN and Elvan Ymtir,RN for their assistance .

REFERENCES
1    Dunn BE, Cohen H, Blaser MJ. Epidemiology of H. Pylori Infection. Clinical Microbiology Reviews 1997; 10: 720-741
2    D'Elios MM, Andersen LP, Prete GD. Inflammation and host response. Current Opinion in Gastroenterology: The year 
      in Helicobacter pylori 1998; 14 (Suppl 1): 15-19
3    Güvener N, Akcan Y, Paksoy I, Soylu AR, Aydyn M, Arslan O. Helicobacter pylori associated gastric pathology in patients 
      with type 2 diabetes mellitus and its relationship with gastric emptying: The Ankara study. Exp Clin Endocrinol Diab 
      1999; 107: 172-176
4    Gentile S, Turco S, Olivero B, Torella R. The role of autonomic neuropathy as a risk factor of Helicobacter pylori infection 
      in dyspeptic patients with type 2 diabetes mellitus. Diab Res Clin Pract 1998; 42: 41-48
5    Xia HHX, Talley JN, Kam EPY, Young LJ, Hammer J, Horowitz M. Helicobacter pylori infection is not associated with 
      diabetes mellitus, nor with upper gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol 
      2001; 96: 1039-1046
6    Simon L, Tornoczky J, Toth M, Jambor M, Sudar Z. The significance of Campylobacter pylori infection in gastroenterologic 
      and diabetic practice. Orvosi Hetilap 1989; 130: 1325-1329
7    Uygur-Bayramiçli O, Kyly D, Yavuzer D, Telatar B, Kavakly B. Helicobacter pylori colonization and immunological disease. 
      Eur J Gastroenterol Hepatol 2001; 13: 301-302
8    Buckley MJ, Scanion C, McGurgan P, O'Morian CA. A validated dyspepsia symptom score. Ital J Gastroenterol Hepatol 
      1997; 29:495-500
9    Delchier JC, Ebert M, Maltfertheiner P. Helicobacter pylori in gastric lymphoma and carcinoma. Current Opinion 
      in Gastroenterology: The year in Helicobacter pylori 1998; 14 (Suppl 1): 41-45
10  Eslick GD, Lim LL-Y, Byles JE, Xia HH, Talley NJ. Association of Helicobacter pylori infection with gastric carcinoma: 
      A meta analysis. Am J Gastroenterol 1999; 94: 2373-2379
11  Wurzer H, Rodrigo L, Stamler D, Archambult A, Rokkas T, Skandalis N, Fedorak R, Bazzoli F, Hentschel E, Mora 
      P, Archmandritis A, Megraud F. For the ACT-10 Study Group. Short course therapy with amoxycillin-clarithromycin 
      triple therapy for 10 days (ACT-10) eradicates Helicobacter pylori and heals duodenal ulcer. Aliment Pharmacol Ther 
      1997; 11: 81-87
12  Viara D, Ali A, Gatta L, O'Morain C. Treatment of Helicobacter pylori. Current Opinion in Gastroenterology: The year 
      in Helicobacter pylori 1998; 14 (Suppl 1): 71-78
13  Gasbarrini A, Ojetti V, Pitocco D, Franceschi F, Candelli M, Torre EL, Gabrielli M, Cammarota G, Armuzzi A, Pola P, 
      Ghirlanda G, Gasbarrini G. Insulin-dependent diabetes mellitus affects eradication rate of Helicobacter pylori infection. 
      Eur J Gastroenterol Hepatol 1999; 11: 713-716
14  Gasbarrini A, Ojetti V, Pitocco D, Armuzzi A, Silveri NG, Pola P, Ghirlanda G, Gasbarrini G. Efficacy of different Helicobacter 
      pylori eradication regimens in patients affected by insulin-dependent diabetes mellitus. Scand J Gastroenterol 
      2000; 35: 260-263
15  Zwet VAA, Megraud F. Diagnosis. Current Opinion in Gastroenterology: The year in Helicobacter pylori 
      1998; 14 (Suppl 1): 27-33
16  Gwilt PR, Nahas RR, Tracewell WG. The effects of diabetes mellitus on pharmocokinetics and pharmacodynamics in 
      humans. Clin Pharmacokinet 1991; 20: 477-490
17  Megraud F. Resistance of Helicobacter pylori to antibiotics. Aliment Pharmacol Ther 1997; 11 (Suppl 1): 43-53
18  Bessman AN, Sapico FL. Infections in the diabetic patient: the role of immune dysfunction and pathogen virulance factors. 
      J Diabetic Complications 1992; 6: 258-262
19  Jaap AJ, Shore AC, Tooke JE. Relationship of insulin resistance to microvascular dysfunction of subjects with 
      fasting hyperglycaemia. Diabetologia 1997; 40: 238-243

Edited by  Xu XQ 

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