Back to Journals » Infection and Drug Resistance » Volume 12

First-line Helicobacter pylori eradication rates are significantly lower in patients with than those without type 2 diabetes mellitus

Authors Yao CC, Kuo CM, Hsu CN, Yang SC, Wu CK, Tai WC, Liang CM, Wu KL, Huang CF, Bi KW, Lee CH, Chuah SK

Received 14 November 2018

Accepted for publication 30 April 2019

Published 29 May 2019 Volume 2019:12 Pages 1425—1431

DOI https://doi.org/10.2147/IDR.S194584

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Joachim Wink

Download Article [PDF] 

Chih-Chien Yao,1 Chung-Mou Kuo,1 Chien-Ning Hsu,2 Shih-Cheng Yang,1 Cheng-Kun Wu,1 Wei-Chen Tai,1 Chih-Ming Liang,1 Keng-Liang Wu,1 Chih-Fang Huang,3 Kuo-Wei Bi,4 Chen-Hsiang Lee,5 Seng-Kee Chuah1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; 2Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung and School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Division of Family physician, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Purpose: To assess the difference of the first-line therapy for Helicobacter pylori in patients with or without type 2 diabetes (DM) and to investigate the clinical factors influencing treatment outcomes.
Patients and methods: In total, 719 patients with H. pylori infection were treated with 7-day standard first-line triple therapy, of whom 182 did and 537 did not have DM. Propensity score matched at a 1:2 ratio – for age, sex and body mass index was performed for the two groups, yielding a DM group with 147 patients and a non-DM group with 249 matched controls for analysis. Urea breath test was performed 6–8 weeks after treatment. Clinical and laboratory parameters were collected for identifying factors associated with failed eradication.
Results: H. Pylori was eradicated in 74.1% (95% confidence interval [CI] =66.2–81.0) of the DM group and 85.3% (95% CI =80.8–89.4) of the non-DM group (p=0.005). Of 51 gastric biopsy samples cultured for H. pylori, 41 were positive. In the DM group, the rates of resistance to amoxicillin, clarithromycin, levofloxacin, and tetracycline were 0%, 50.0%, 50.0% and 0%, respectively. In the non-DM group, the comparable proportions were 2.9%, 17.1%, 22.9%, and 0%, respectively. Univariate analysis revealed that DM (Odds ratio [OR], 1.771, 95% CI, 1.167–2.668, p=0.006), clarithromycin resistance (OR, 15.273; 95% CI, 1.687–138.269; p=0.015), and amoxicillin resistance (OR, 4.672; 95% CI, 2.431–8.979; p<0.001) were independently associated with failure to eradicate H. pylori. Multivariate analysis showed that clarithromycin resistance was the major factor independently associated with failure of eradication (OR, 25.472; 95% CI, 1.549–418.956; p=0.023).
Conclusions: First-line H. pylori eradication rates in patients with DM were significantly lower than in those without DM, although neither group achieved >90% eradication.

Keywords: Helicobacter pylori infection, standard triple therapy

Introduction

Helicobacter pylori infection affects approximately 50% of the world’s population.14 The World Health Organization classified H. pylori as a grade I carcinogen, and the major risk factor of peptic ulcer diseases. Chronic gastritis attributed to the organism can progress through the pre malignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then gastric cancer.58 Hence, successful eradication is a major issue with the potential to influence patient outcomes.

Recent studies have explored significant association between H. pylori infection and extragastric diseases such as cardiovascular disease, metabolic syndrome and certain liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, liver fibrosis and cirrhosis.9 The involved pathogenesis is chronic inflammation and immune responses on the local and systemic level.10 Since more convincing evidences are still an unmet need on this issue, it is therefore worth further investigation.

A higher prevalence of H. pylori infection in patients with type 2 diabetes mellitus (DM) has been reported in previous studies.1114 In addition, some have investigated the influence of H. pylori infection on the glucose control in a diabetic cohort of patients with DM.15,16 However, there are limited studies regarding eradication rates of H. pylori in patients with DM, and the findings have been inconsistent.1719 Therefore, we aimed to assess the difference of the first line H. pylori in patients with or without type 2 DM and to investigate the clinical factors influencing treatment outcomes.

Patients and methods

Patients

We assessed records of 719 patients who were treated for H. pylori infection with standard first-line triple therapy (Proton-pump inhibitor twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily for 7 days) between January 1, 2013 and December 31, 2014 at outpatient clinics in Kaohsiung Chang Gung Memorial Hospital, Taiwan. All patients were at least 18 years of age and had undergone endoscopy that showed either peptic ulcers or gastritis. H. pylori infection was diagnosed by histological assessment of endoscopic biopsy specimens of gastric mucosa. Records of patients with a history of previous H. Pylori eradication, antibiotics administration within 3 months prior to endoscopy, gastric malignancy, who were lost to follow-up or had incomplete records, or who were treated by 7-day non-bismuth containing quadruple therapy were also excluded.

Of the 719 patients for whom records were available, 182 had DM and 537 did not. To minimize potential selection bias between the two groups, we employed propensity score matching (PSM) with the covariates age, gender, and body mass index (BMI). Using a greedy matching algorithm, the groups were matched in a 1:2 ratio, resulting in 147 patients in the DM group and 279 in the non-DM control group.

The criteria for the diagnosis of DM were 1) a fasting blood glucose level greater than or equal to 126 mg/dl on two occasions; 2) a hemoglobin A1c level greater than or equal to 6.5% on two occasions; 3) a random blood glucose level greater than or equal to 200 mg/dl with classic symptoms of hyperglycemia.

Outcomes and follow-up

The primary outcome of interest was the successful eradication of H. pylori. Failure of eradication by first-line therapy was confirmed after treatment by either one positive 13C-urea breath test or any two positive results of the rapid urease test, histology or culture when repeating the testing twice. According to our hospital requirements, all patients were followed to assess drug compliance and adverse effects as soon as they finished their medications. Then, they underwent either an endoscopy or a urea breath test 6–8 weeks later. Failure to finish 80% of all medication due to adverse effects was considered poor compliance.20,21

Demographic information recorded from the electronic medical records included age, gender, BMI, history of smoking, alcohol consumption, previous peptic ulcer history, duration of DM, medications, and laboratory data (fasting glucose sugar, HbA1c, lipid profile).

Culture and antimicrobial resistance

One antral gastric and one corpus biopsy specimen were obtained from 51 patients for H. pylori isolation using previously described culture methods.20 The biopsy specimens were cultured on plates containing Brucella chocolate agar with 7% sheep blood and incubated for 4–5 days under micro-aerobic conditions. The minimal inhibitory concentration (MIC) was determined by the agar dilution test. H. pylori strains with MIC values ≥0.5, ≥1, ≥1, ≥4 and ≥8 mg/L were considered to be resistant to amoxicillin, clarithromycin, levofloxacin, tetracycline and metronidazole , respectively.21

Statistical analysis

The primary outcome variables were the eradication rate, occurrence of adverse events, and level of patient compliance. Using the SPSS program (Statistical Package for the Social Sciences version 20, IBM Corporation, Armonk, NY, USA), Chi-square tests with or without Yates’ correction for continuity and Fisher’s exact tests were used when appropriate to compare the outcomes between groups. Eradication rates were analyzed for all included patients. We also excluded patients with unknown H. pylori status following therapy and those with major protocol violations. A p-value <0.05 was considered statistically significant. To determine the independent factors that affected treatment response, clinical and laboratory parameters were analyzed after PSM for age, gender, and BMI by univariate and multivariate analysis.

Results

The demographic data of the two groups before and after PSM are summarized in Table 1. Before PSM, the mean age of patients in the DM group was higher than in the non-DM group, but there was no significant difference among any covariates in the groups after PSM. The duration of DM was 8.1±5.9 years and 80.8% (147/182) of the patients were taking oral antihyperglycemic drugs. Only three patients (1.6%) needed Insulin monotherapy, while six took both an oral antihyperglycemic drug and insulin. The eradication rates attained in the DM and non-DM groups before PSM were 75.3% (95% confidence interval (CI) =68.4–81.4) and 84.4% (95% CI =81.1–87.4) (p=0.006) and 74.1% (95% confidence interval (CI) =66.2–81.0) and 85.3% (95% CI =80.8.8–89.4) (p=0.005) (Table 2). Samples from 51 patients were cultured for H. pylori, yielding 41 positive cultures. In the DM group, the rates of resistance to the antibiotics were amoxicillin, 0% (0/6); clarithromycin, 50.0% (3/6); levofloxacin, 50.0% (3/6); and tetracycline, 0% (0/6). In the non-DM group, the rates of resistance were amoxicillin, 2.9% (1/35); clarithromycin, 17.1% (6/35); levofloxacin, 22.9% (8/35); and tetracycline, 0 % (0/35).

Table 1 Baseline characteristics of patients with and without DM

Table 2 Major outcomes of H. pylori eradication therapy

Adverse events

The incidence of adverse events did not differ significantly between the two groups (DM 4.1% vs non-DM 6.5%, p=0.313) (Table 3). The adverse events included abdominal pain, constipation, diarrhea, dizziness, headache, nausea or vomiting, and skin rash. In the DM group, two patients had abdominal pain (1.4%), two (1.4%) had constipation, two had loose stool passage (1.4%) and one (0.7%) had nausea; In the non-DM group, four patients (1.4%) had abdominal pain, five patients (1.8%) had constipation, seven patients (2.5%) had loose stool passage, three (1.1%) had dizziness, one (0.4%) had headache and two (0.7%) had nausea. These adverse events were mild and did not disturb the patients’ daily activities.

Table 3 Adverse events of the H. pylori treatment regimen after matching

Factors influencing the efficacy of anti-H. pyloritherapy

On univariate analysis, factors independently associated with failure to eradicate H. pylori included DM (Odds ratio [OR], 1.771, 95% CI, 1.167–2.668, p=0.006), clarithromycin resistance (OR, 15.273; 95% CI, 1.687–138.269; p=0.015 and amoxicillin resistance (OR, 4.672; 95% CI, 2.431–8.979; p<0.001) (Table 4). Multivariate analysis showed that clarithromycin resistance was the major factor independently associated with failure of H. pylori eradication (OR, 25.472; 95% CI, 1.549–418.956; p=0.023) (Table 5).

Table 4 Univariate analysis of factors associated with failure of H. pylori eradication

Table 5 Multivariate analysis of the clinical factors associated with failure of H. pylori eradication

Discussion

H. pylori infection is the major risk factor in peptic ulcer disease. Successful eradication of H. pylori has greatly reduced the recurrence of peptic ulcers as well as the incidence of atrophic gastritis and gastric cancer. Reports on H. pylori infection in DM have had conflicting findings. Some studies have shown a higher prevalence of H. pylori infection in patients with DM, while others have found no difference.11,14,22,23 In a large, well-designed study by Xia et al,24 there was no difference in H. pylori seroprevalence between patients with DM and non-DM controls. Reports on the effect of H. pylori infection on the glucose control of diabetes measured by HbA1c or insulin resistance have also yielded inconsistent findings,15,25,26 as have studies of the success rate of first line eradication in patients with DM.12,18,19 In the present study, the eradication rate with standard triple therapy in the non-DM group was 84.4% before and 85.3% after PSM, results which are compatible with results in Taiwan 5 years previously.27

Some investigations have found that eradication rates of H pylori in patients with type I diabetes were lower than in non-DM patients.26,28,29 For instance, Gasbarrini et al26 showed that the H. pylori eradication rate with 7-day standard triple therapy comprising amoxicillin, clarithromycin, and pantoprazole was 65% in patients with type I diabetes compared with 92% in non-DM controls in 1999. They suggested that patients with insulin-dependent DM often had chronic infections which might lead to poor antibiotic absorption. However, reports on factors influencing H. pylori eradication in type 2 DM have been inconsistent. In our study after PSM, patients with DM treated with 7-day standard triple therapy had significantly lower eradication rates than the non-DM control group (74.1% vs 85.3%, p=0.005). This is consistent with previous reports that standard triple therapy conferred lower eradication rates in patients with DM.17,18,30,31,32 For example, Sargýn et al30 reported eradication in 50% of patients with diabetes versus 85% in the control group by prescribing a 10-day standard triple therapy (p<0.001). In another study by Vafaeimanesh et al,17 the 14-day regimens yielded H. pylori eradication rate of 63% in the DM group and 87.7% in the control group (p=0.017).

Several proposed mechanisms may explain the low eradication rate of H. pylori eradication in DM patients. First, DM impairs the immune system to a variable extent.33,34Second, patients with DM are more susceptible to bacterial and mycotic infections, leading to frequent use of antibiotics, which may in turn contribute to the development of resistance.35,36 Third, diabetes may impair gastric mucosal microvasculature, leading to reduction in antibiotics absorption.37 Fourth, it is very likely that the more frequent use of multiple antibiotics in these patients may ultimately lead to H. pylori-resistant strains, like the high rate of clarithromycin resistance in this study. Finally, re-infection after bacterial eradication, although rarely observed in the general population, seems to be more frequent in patients with diabetes than in controls.38 Nevertheless, we were unable to assess the actual re-infection rate in this study due to its retrospective nature.

We performed univariate and multivariate analysis to assess factors independently associated with H. pylori eradication. On univariate analysis, a diagnosis of DM, and clarithromycin or amoxicillin resistance were factors associated with failure of H. pylori eradication. On multivariate analysis, clarithromycin resistance was the only significant factor associated with lack of H. pylori eradication. The clarithromycin resistance rate in the DM patients was very high compared with non-DM group. It was also higher than in the general population in Taiwan, reported by Liou et al 39only 7.9%. It was probably one of the main causes for the lower H. pylori eradication rate in our DM group, which was consistent with that in the report by Demir et al.32As noted above, it is likely that poor eradication rates among patients with DM may be attributed to factors such as decreased immunocompetence, increased antibiotic resistance because of frequent antibiotic use, and poor gastric absorption. Another study by Demir et al19 from Turkey reported that the eradication rate with triple therapy was only 51% in patients with DM, which was very likely associated with the high clarithromycin resistance rate of 40%.19 They had much better results with a 14-day clarithromycin-free regimen including pantoprazole (40 mg b.i.d.), bismuth citrate (400 mg b.i.d.), tetracycline (500 mg q.i.d.), and metronidazole (500 mg b.i.d.), which succeeded in eradicating H. pylori in 85% of the DM group and 87% of the non-DM group.

This study encountered some limitations. First, this was a retrospective study in a single medical center. Second, 7-day standard triple therapy was used in this study during our study period from January 2013 to December 2014. This was because first-line clarithromycin triple therapy was reimbursable for only 7 days under the Taiwan National Health Insurance System even until now. However, 10–14 day reports with standard triple therapies reported in the literature showed that this regimen was also suboptimal in this DM patient cohort. However, very high clarithromycin resistance was observed in the patients with DM and was the major factor independently associated with failure of H. pylori eradication. It is an important message that there are still unmet needs in the treatment of H. Pylori infection in patients with DM, given the limited number of studies focusing on this population. Ataseven et al40 reported a disappointing <60% eradication rate for 14-day sequential therapy in patients with type 2 DM. Demir et al showed that the bismuth-based quadruple eradication regimen as first-line therapy attained 85% eradication.19Clearly more evidences are required to clarify the best treatment in these patients.

Conclusions

This study found that first-line H. pylori eradication rates in patients with DM were significantly lower than in those without DM, although neither group achieved >90% eradication. Studies seeking for optimal novel first line H. pylori regimens for diabetic patients are mandatory.

Ethics approval and informed consent

The data in this study were collected from computerized medical charts. This study was approved by both the Institutional Review Board and Ethics Committee of Chang Gung Memorial Hospital, Taiwan (IRB 201801207B0). The Ethics Committee waived the requirement for informed consent, and each patient’s medical records were anonymized and deidentified prior to access. None of the patients were minors. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee.

Acknowledgments

The authors would like to acknowledge Miss Ching-Yi Lin for her assistance in this study.

Author contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Cave DR. How is Helicobacter pylori transmitted? Gastroenterology. 1997;113(6 Suppl):S9–S14.

2. Mentis A, Lehours P, Megraud F. Epidemiology and diagnosis of Helicobacter pylori infection. Helicobacter. 2015;20(Suppl 1):1–7. doi:10.1111/hel.12250

3. World Health Organization, International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 61, Schistosomes, Liver Flukes and Helicobacter Pylori. Lyon: IARC; 1994:177–240.

4. Graham DY. Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: a model. Gastroenterology. 1997;113:1983–1991.

5. Bin L, Meng L. Helicobacter pylori eradication for preventing gastric cancer. World J Gastroenterol. 2014;20:5660–5665. doi:10.3748/wjg.v20.i19.5660

6. Correa P, Piazuelo MB. The gastric precancerous cascade. J Dig Dis. 2012;13:2–9. doi:10.1111/j.1751-2980.2011.00550.x

7. Rugge M, Genta RM, Di Mario F, et al. Gastric cancer as preventable disease. Clin Gastroenterol Hepatol. 2017;15(12):1833–1834. doi:10.1016/j.cgh.2017.05.023

8. Mommersteeg MC, Yu J, Peppelenbosch MP, Fuhler GM. Genetic host factors in Helicobacter pylori-induced carcinogenesis: emerging new paradigms. Biochim Biophys Acta Rev Cancer. 2018;1869(1):42–52. doi:10.1016/j.bbcan.2017.11.003

9. Waluga M, Kukla M, Żorniak M, Bacik A, Kotulski R. From the stomach to other organs: Helicobacter pylori and the liver. World J Hepatol. 2015;7:2136–2146. doi:10.4254/wjh.v7.i18.2136

10. Trinchieri G. Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol. 2012;30:677–706. doi:10.1146/annurev-immunol-020711-075008

11. Tseng CH. Diabetes, insulin use and Helicobacter pylori eradication: a retrospective cohort study. BMC Gastroenterol. 2012;12:46. doi:10.1186/1471-230X-12-160

12. Vafaeimanesh J, Parham M, Seyyedmajidi M, et al. Helicobacter pylori infection and insulin resistance in diabetic and nondiabetic population. Sci World J. 2014;2014:391250. doi:10.1155/2014/391250

13. Kayar Y, Pamukcu O, Eroglu H, et al. Relationship between Helicobacter pylori infections in diabetic patients and inflammations, metabolic syndrome, and complications. Int J Chronic Dis. 2015;2015:290128.

14. Han X, Li Y, Wang J, et al. Helicobacter pylori infection is associated with type 2 diabetes among a middle- and old-age Chinese population. Diabetes Metab Res Rev. 2016;32:95–101. doi:10.1002/dmrr.2677

15. Bonfigli AR, Boemi M, Festa R, et al. Randomized, double-blind, placebo-controlled trial to evaluate the effect of Helicobacter pylori eradication on glucose homeostasis in type 2 diabetic patients. Nutr Metab Cardiovasc Dis. 2016;26:893–898. doi:10.1016/j.numecd.2016.06.012

16. Chen Y, Blaser MJ. Association between gastric Helicobacter pylori colonization and glycated hemoglobin levels. J Infect Dis. 2012;205:1195–1202. doi:10.1093/infdis/jis106

17. Vafaeimanesh J, Rajabzadeh R, Ahmadi A, et al. Effect of Helicobacter pylori eradication on glycaemia control in patients with type 2 diabetes mellitus and comparison of two therapeutic regimens. Arab J Gastroenterol. 2013;14:55–58. doi:10.1016/j.ajg.2013.03.002

18. Cho DK, Park SY, Kee WJ, et al. [The trend of eradication rate of Helicobacter pylori infection and clinical factors that affect the eradication of first-line therapy]. Korean J Gastroenterol. 2010;55:368–375. 201006254

19. Demir M, Gokturk S, Ozturk NA, et al. Bismuth-based first-line therapy for Helicobacter pylori eradication in type 2 diabetes mellitus patients. Digestion. 2010;82:47–53. doi:10.1159/000236024

20. Chuah SK, Hsu PI, Chang KC, et al. Randomized comparison of two on-bismuth-containing second-line rescue therapies for Helicobacter pylori. Helicobacter. 2012;17:216–223. doi:10.1111/j.1523-5378.2012.00937.x

21. Chuah SK, Liang CM, Lee CH, et al. A randomized control trial comparing two levofloxacin-containing second-line therapies for Helicobacter pylori eradication. Medicine (Baltimore). 2016;95:e3586. doi:10.1097/MD.0000000000004864

22. Hamrah MS, Hamrah MH, Ishii H, et al. Association between Helicobacter pyloriinfection and cardiovascular risk factors among patients in the Northern part of Afghanistan: a cross-sectional study in Andkhoy City. Asian Pac J Cancer Prev. 2018;19:1035–1039. doi:10.22034/APJCP.2018.19.4.1035

23. Den Hollander WJ, Broer L, Schurmann C, et al. Helicobacter pyloricolonization and obesity – a Mendelian randomization study. Sci Rep. 2017;7(1):14467. doi:10.1038/s41598-017-14106-4

24. Xia HHN, Talley NJ, Kam EPY, et al. Helicobacter pylori infection is not associated with diabetes mellitus, nor with upper gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol. 2001;96:1039–1046. doi:10.1111/j.1572-0241.2001.03604.x

25. Wada Y, Hamamoto Y, Kawasaki Y, et al. The eradication of Helicobacter pyloridoes not affect glycemic control in Japanese subjects with type 2 diabetes. Jpn Clin Med. 2013;4:41–43. doi:10.4137/JCM.S10828

26. Gasbarrini A, Ojetti V, Pitocco D, et al. Insulin-dependent diabetes mellitus affects eradi cation rate of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 1999;11:713–716.

27. Wu IT, Chuah SK, Lee CH, et al. Five-year sequential changes in secondary antibiotic resistance of Helicobacter pylori in Taiwan. World J Gastroenterol. 2015;21(37):10669–10674. doi:10.3748/wjg.v21.i37.10669

28. Gasbarrini A, Ojetti V, Pitocco D, et al. Efficacy of different Helicobacter pylori eradication regimens in patients affected by insulin-dependent diabetes mellitus. Scand J Gastroenterol. 2000;35:260–263.

29. Bégué RE, Gómez R, Compton T, Vargas A. Effect of Helicobacter pylori eradication in the glycemia of children with type 1 diabetes: a preliminary study. South Med J. 2002;95:842–845. doi:10.1097/00007611-200295080-00012

30. Sargyn M, Uygur-Bayramicli O, Sargyn H, et al. Type 2 diabetes mellitus affects eradication rate of Helicobacter pylori. World J Gastroenterol. 2003;9:1126–1128.

31. Demir M, Gokturk HS, Ozturk NA, et al. Efficacy of two different Helicobacter pylorieradication regimens in patients with type 2 diabetes and the effect of Helicobacter pylori eradication on dyspeptic symptoms in patients with diabetes: a randomized controlled study. Am J Med Sci. 2009;338:459–464. doi:10.1097/MAJ.0b013e3181b5d3cf

32. Demir M, Gokturk HS, Ozturk NA, et al. Clarithromycin resistance and efficacy of clarithromycin-containing triple eradication therapy for Helicobacter pylori infection in type 2 diabetes mellitus patients. South Med J. 2009;102:1116–1120. doi:10.1097/SMJ.0b013e3181bca538

33. Unger RH, Foster DW. Diabetes mellitus. In: Wilson JD, Foster DW, editors. Williams’ Text-Book of Endocrinology. 8 ed. Philadelphia: Saunders; 1992:1255–1333.

34. Marhoffer W, Stein M, Maeser E, Federlin K. Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care. 1992;15:256–260. doi:10.2337/diacare.15.2.256

35. Gwilt PR, Nahas RR, Tracewell WG. The effects of diabetes mellitus on pharmocokinetics and pharmacodynamics in humans. Clin Pharmacokinet. 1991;20:477–490. doi:10.2165/00003088-199120060-00004

36. Megraud F. Resistance of Helicobacter pylori to antibiotics. Aliment Pharmacol Ther. 1997;11(Suppl 1):43–53.

37. Jaap AJ, Shore AC, Tooke JE. Relationship of insulin resistance to microvascular dysfunction of subjects with fasting hyperglycaemia. Diabetologia. 1997;40:238–243. doi:10.1007/s001250050669

38. Marietti M, Gasbarrini A, Saracco G, Pellicano R. Helicobacter pylori infection and diabetes mellitus: the 2013 state of art. Panminerva Med. 2013;55:277–281.

39. Liou JM, Chang CY, Chen MJ, et al. The primary resistance of Helicobacter pylori in Taiwan after the national policy to restrict antibiotic consumption and its relation to virulence factors—a nationwide study. PLoS One. 2015;10:e0124199. doi:10.1371/journal.pone.0124199

40. Ataseven H, Demir M, Gen R. Effect of sequential treatment as a first-line therapy for Helicobacter pylori eradication in patients with diabetes mellitus. South Med J. 2010;10:988–992. doi:10.1097/SMJ.0b013e3181eea6cc

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]