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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
123
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
123
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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