STOMACH

Helicobacter pylori Prevalence in Diabetes Mellitus Patientswith Dyspeptic Symptoms and Its Relationship to GlycemicControl and Late Complications

Mehmet Demir Æ Huseyin Savas Gokturk Æ Nevin Akcaer Ozturk ÆMustafa Kulaksizoglu Æ Ender Serin Æ Ugur Yilmaz

Received: 24 November 2007 / Accepted: 20 December 2007 / Published online: 5 March 2008

� Springer Science+Business Media, LLC 2008

Abstract Background There are contradictory reports on

Helicobacter pylori prevalence and its relationship to late

complications of diabetes mellitus (DM). The aim of this

study was to determine the prevalence of H. pylori infection

in type 2 DM patients and to evaluate the relationship

between H. pylori infection and the glycemic control, late

complications. Material and Method A total of 141 type 2

DM patients and 142 nondiabetic subjects with upper gas-

trointestinal symptoms were enrolled in the study. All

patients underwent upper gastrointestinal endoscopy with

biopsy specimens obtained from gastric antrum and corpus.

H. pylori status was evaluated in each patient by both the

rapid urease test and histopathological examination. Plasma

glucose, HbA1c, microalbuminuria in 24 h collected urine,

electroneuromyography, and fundoscopic examinations

were performed in all subjects. Results The prevalence of

H. pylori infection was 61.7% and 58.5%, respectively,

among type 2 diabetic patients and nondiabetic controls and

was not statistically significant (P = 0.577). The duration of

diabetes, fasting blood glucose and haemoglobin A1c levels,

nephropathy and retinopathy prevalence did not differ sig-

nificantly between the two groups (diabetics versus

nondiabetics). There was no late complication in 60.3% of

the type 2 diabetic patients as compared to at least one late

complication in the remainders. A statistically significant

correlation was found between H. pylori infection and the

presence of neuropathy (P = 0.021). Conclusions The

prevalence of H. pylori infection did not differ significantly

between the diabetic patients and nondiabetic controls.

Interestingly, diabetics with H. pylori infection had a higher

incidence of neuropathy, although there was no association

between the duration and regulation of diabetes, retinopathy,

nephropathy and H. pylori status.

Keywords Helicobacter pylori � Diabetes mellitus �Prevalence � Complication

Introduction

Helicobacter pylori infection affects approximately 50% of

the world’s population [1] and is recognized as the major

acquired factor in the pathogenesis of chronic antral gastritis,

peptic ulcer disease, and gastric cancer. Identification of risk

groups is very important in this respect. Impairment of

immune system is thought to be responsible for more frequent

and severe infections in diabetic patients [2]. Additionally,

bacterial overgrowth in the upper gastrointestinal tract due to

delayed gastric emptying has been suggested [3, 4]. There are

contradictory reports on H. pylori prevalence among diabetic

patients as high [5–7], low [8], or normal [9–12] compared to

M. Demir � H. S. Gokturk � N. A. Ozturk

Department of Gastroenterology, Baskent University Faculty

of Medicine, Konya, Turkey

H. S. Gokturk (&)

Department of Gastroenterology, Konya Uygulama ve Arastırma

Merkezi, Baskent University, Saray Cad. No:1, Konya 42080,

Turkey

e-mail: savasgokturk@yahoo.com

M. Kulaksizoglu

Department of Endocrinology and Metabolism, Baskent

University Faculty of Medicine, Konya, Turkey

E. Serin

Department of Gastroenterology, Baskent University Faculty

of Medicine, Adana, Turkey

U. Yilmaz

Department of Gastroenterology, Baskent University Faculty

of Medicine, Ankara, Turkey

123

Dig Dis Sci (2008) 53:2646–2649

DOI 10.1007/s10620-007-0185-7

control subjects. Moreover, the relationship between H.

pylori infection and late complications of diabetes mellitus

(DM) is not clear. The aim of this study was to determine the

H. pylori infection prevalence in type 2 DM patients and to

evaluate the relationship between H. pylori infection and

glycemic control (hemoglobin A1c, fasting blood glucose),

the late complications of diabetes mellitus such as diabetic,

nephropathy, retinopathy and peripheral neuropathy.

Material and Methods

The study involved 141 consecutive type 2 DM patients (97

female, 44 male, mean age 52 ± 8.2 years) and 142 nondi-

abetic subjects (92 female, 40 male, mean age 51 ± 9.3

years) with upper gastrointestinal symptoms for at least

6 months between the June 2004 and May 2005 in the gas-

troenterology clinics of Baskent University Konya Hospital.

According to the diagnostic criteria of diabetes mellitus as

defined by the American Diabetes Association, only patients

with a fasting blood glucose above 126 mg/dL or second-

hour oral glucose tolerance testing above 200 mg/dL were

considered as diabetic. Exclusion criteria were: prior H.

pylori eradication therapy, use of antibiotics or antisecretory

therapy in the preceding 6 months, history of gastric surgery

or cholecystectomy, decompensated congestive heart fail-

ure, chronic renal failure requiring dialysis treatment,

diagnosis of malignancy, and active infection requiring an-

tibiotherapy. All patients underwent upper gastrointestinal

endoscopy with biopsy specimens obtained from gastric

antrum and corpus. H. pylori status was evaluated in each

patient by both the rapid urease test and histopathological

examination (Giemsa stain) of the antrum and corpus biopsy

specimens. Plasma glucose and HbA1c levels after 12 h

fasting, microalbuminuria in 24 h collected urine specimen,

electroneuromyography, and fundoscopic examinations

were obtained from all subjects.

The study was approved by the local ethics committee

of Baskent University and each patient gave informed

consent in accordance with the Helsinki Declaration.

Statistical Analysis

Data were statistically analysed using SPSS version 13.0

(Statistical SPSS Inc., Chicago, IL, USA). Statistically

significant differences between groups were assessed using

either the Student t-test or the v2 test. P-values below 0.05

were considered significant in all analysis.

Results

Of the diabetic patients, 97 (68.8%) were women and 44

(32.2%) were men with a mean age of 52 ± 8.2 years.

Gender and mean age did not differ significantly between

the two groups (diabetics versus nondiabetics). The prev-

alence of H. pylori infection was 61.7% (87/141) and

58.5% (83/142), respectively, among type 2 diabetic

patients and nondiabetic controls and the difference

between the groups was not statistically significant

(P = 0.577). There was no late complication in 60.3% (85/

141) of the type 2 diabetic patients as compared to at least

one late complication in the remaining 39.7% (56/141).

With regard to the duration of the diabetes, fasting blood

glucose and haemoglobin A1c levels, nephropathy and

retinopathy prevalence, no statistically significant differ-

ence have been reported among the diabetics according to

H. pylori status. A statistically significant difference was

detected between H. pylori infection and the presence of

neuropathy (P = 0.021). Of these 141 patients, 128

(90.7%) had reported a history of diabetes mellitus and 13

(9.2%) were newly diagnosed. Diabetic patients had been

treated with oral antidiabetics in 54 (38.3%), insulin in 41

(29.1%), a combination of oral antidiabetics and insulin in

30 (21.3%), and diet alone in 16 (10.21%). The mean

duration of diabetes was 6.1 ± 5.9 years. Of the nondia-

betic control patients, 92 (64.8%) were women and 50

(36.2%) were men with a mean age of 51 ± 9.3 years. The

mean age and the sex were not significantly different

among the diabetics and the nondiabetic controls. H. pylori

infection was detected in 61.7% (87/141) and 58.5% (83/

142) of the diabetics and nondiabetics, respectively, and

the difference between the two groups was not statistically

significant (P = 0.577) (Table 1). There was no late

complication in 60.3% (85/141) of type 2 diabetic patients

as compared to at least one late complication (nephropathy,

retinopathy or peripheral neuropathy) in the remaining

39.7% (56/141). Additionally, no difference in the age, sex,

duration of diabetes, fasting blood glucose, HbA1c,

nephropathy, and retinopathy were observed between

infected and noninfected diabetic patients (P [ 0.05). The

correlation between the presence of H. pylori infection and

the peripheral neuropathy was statistically significant

(P = 0.02). Demographic and clinical characteristics of

diabetic patients with H. pylori and those without H. pylori

are shown in Table 2.

Table 1 Helicobacter pylori prevalence and demographics of the

diabetic patients and controls

DM, n (%) Control, n (%) P

Age (years) 52 ± 8.2 51 ± 9.3 NS

Sex

Male 44 (32.2%) 50 (35.2%) NS

Female 97 (68.8%) 90 (65.8%) NS

H. Pylori 87/141 (61.7%) 83/142 (58.5%) NS

DM, type 2 diabetes mellitus; NS, not significant

Dig Dis Sci (2008) 53:2646–2649 2647

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Discussion

There is little and equivocal available data about the rela-

tionship between H. pylori infection and diabetes mellitus

in the literature [5–12]. Some previous reports, based on

serologic antibody detection, have found a high prevalence

of H. pylori infection among diabetics as compared to the

general population [5–7]. On the other hand, another study

with histopathological demonstration of microorganism,

described a minor role of H. pylori infection among upper

gastrointestinal pathologies [8]. Four recent studies did not

detect a relationship between H. pylori infection and dia-

betes mellitus [9–12]. The prevalence of H. pylori

infection ranged between 30% and 80% in the previously

reported eight studies [5–12]. Discordant results among the

studies may be related to the epidemiological distribution

of infection, nonhomogenous patient groups or the diver-

sity of the methods used in the studies.

We used both the rapid urease test and histopathological

examination for the diagnosis of H. pylori infection and the

prevalence of H. pylori infection among type 2 DM

patients and nondiabetic controls was 61.7% (87/141) and

58.5% (83/142) respectively. No statistically significant

correlation was detected (P = 0.577).

It is well known that diabetic patients are prone to chronic

infections, considered as a consequence of impairment of

cellular and humoral immunity. Furthermore, it has been

suggested that delayed gastric emptying (gastroparesis dia-

beticorum) may predispose to bacterial overgrowth in the

upper gastrointestinal tract and consequently this may be

considered as a risk factor for H. pylori infection [3, 4, 13].

To our knowledge, there are no available data in the literature

concerning a possible flora existing in the stomach of the DM

patients. On the other hand, H. pylori colonization and sus-

tained infection due to the impaired cellular immune

response in acquired immune deficiency syndrome (AIDS)

has been reported [14, 15]. Achlorhydria and diminished

secretion of hydrochloric acid are more frequent among

diabetic patients and thought to have an unfavorable effect

on H. pylori [16–19]. It is also known that impaired leuko-

cyte function and hyperglycemia in diabetes mellitus

predispose to infections and resultant increased antibiotic

use may inhibit the colonization of H. pylori. A complicated

balance between predisposing (e.g., gastroparesis diabeti-

corum) and preventing factors (e.g., achlorhydria due to

diabetes mellitus) determine the prevalence of H. pylori

infection in diabetes mellitus. It is controversial whether the

prevalence of H. pylori is related to the duration of diabetes

mellitus [5, 10, 20, 21]. A study from Italy reported that the

rate of H. pylori infection increased with the duration of

diabetes mellitus (\1 year, 23%; 1–3 years, 32%;[3 years,

40%). However, study groups were not homogenous in terms

of mean age [5]. On the contrary, another study from Spain

suggested that the seroprevalence of H. pylori decreases

with insulin dependent diabetes mellitus (IDDM) duration.

Another study with 63 type 2 DM patients reported no

association between HP infection, glycemic status, and

duration of diabetes in diabetic subjects [12]. In our study,

there was no correlation between prevalence of H. pylori and

the duration of DM or age (P [ 0.05). Eventually, our results

are consistent with previous studies reporting that the dura-

tion of diabetes and impairment of immune functions during

this chronic disease may lead to increase in the prevalence of

H. pylori infection in this patient population.

The literature about the late complications of DM and the

prevalence of H. pylori is scarce. A statistically significant

association was detected between H. pylori and peripheral

neuropathy (P = 0.02) but not with nephropathy and reti-

nopathy (P [ 0.05) in our study. In a recent report, similar to

our results, no significant association was detected between

H. pylori and retinopathy and nephropathy [7]. There is much

more data available regarding neuropathy than other late

complications. Mallecki et al. [8] reported that HP infection in

diabetics with neuropathy was significantly lower than in

Table 2 Clinical and

epidemiological characteristics

of diabetic patients according to

H. pylori (HP) infection status

NS, not significant

Diabetes mellitus

HP (+) HP (-) P

Age (years) 53 ± 10.1 52 ± 10.2 NS

Sex

Male (n) 29 15 NS

Female (n) 58 39

Duration of diabetes 5.9 ± 6.1 6.28 ± 5.9 NS

Fasting blood glucose 165 ± 64.6 160 ± 8.261.8 NS

HbA1c 7.9 ± 1.8 8.7 ± 7.1 NS

Late complications of diabetes

Nephropathy (%) (n) 17.2 (15/87) 11.1 (6/54) NS

Retinopathy (%) (n) 18.3 (16/87) 16.6 (9/54) NS

Peripheral neuropathy (%) (n) 35.6 (31/87) 16.6 (9/54) P \ 0.05

2648 Dig Dis Sci (2008) 53:2646–2649

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diabetics without neuropathy (29% versus 35%). In a report by

Perisco et al. [22], no change in H. pylori infection was

detected among neuropathic and nonneuropathic subjects.

However in this study, a relatively low number of subjects

without a control group was studied. In another study, H.

pylori infection was detected in 94% of patients with auto-

nomic neuropathy but in only 34% of those without autonomic

neuropathy [4]. Gulcelik et al. [7] also reported similar H.

pylori prevalence rates of 90.6% versus 44%. Impaired gastric

emptying, as a result of diabetic autonomous neuropathy, and

bacterial overgrowth have been suggested as underlying rea-

sons for high H. pylori prevalence. On the other hand, Kao

et al. [23] reported a similar H. pylori prevalence among

those with both delayed and normal gastric emptying times

(62% versus 56%). Current literature suggests an association

between H. pylori and the autonomous neuropathy but the

physiopathological mechanism to explain this relationship is

not clear yet. There is no available data about the relationship

between H. pylori and peripheral neuropathy. In our study,

peripheral neuropathy was more common among diabetic

patients with H. pylori regardless of glycemic control and

duration of the DM. Recent studies suggest that H. pylori

infection might be associated with deficiency of vitamin B12

(cobalamin). Not only atrophic gastritis secondary to H.

pylori infection but also the malabsorbtion of the cobalamin

have been suggested as causative factors [9, 10, 24]. In the

present study, vitamin B12 levels were not studied. Prospec-

tive studies would be advisable to evaluate the relationship

between H. pylori infection, metabolism of vitamin B12, and

diabetic neuropathy.

In conclusion, the present study suggests that H. pylori

infection is not increased in type 2 diabetes mellitus as

compared to the control group and appears not to be

associated with glycemic control and late complications of

diabetes mellitus such as retinopathy and neuropathy. Our

study identifies a significant correlation between H. pylori

and diabetic peripheral neuropathy and further studies will

be needed to confirm and clarify these findings.

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