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Helicobacter pylori infection in diabetic patients: prevalence and endoscopic findings
European Journal of Internal Medicine 13 (2002) 376–379 www.elsevier.com / locate / ejim
Original article
Helicobacter pylori infection in diabetic patients: prevalence and endoscopic findings a, a b c Roussos Anastasios *, Constantin Goritsas , Christos Papamihail , Rodoula Trigidou , b a Peter Garzonis , Angeliki Ferti a
Department of Internal Medicine, General Regional Hospital ‘ Sotiria’, Athens, Greece b Endoscopy Department, General Regional Hospital ‘ Sotiria’, Athens, Greece c Department of Pathology, General Regional Hospital ‘ Sotiria’, Athens, Greece
Received 28 August 2001; received in revised form 13 November 2001; accepted 15 November 2001
Abstract Background: In patients with diabetes mellitus, chronic infections are frequent and severe, due to the impairment of their immune status. However, data on the prevalence of Helicobacter pylori (H. pylori) infection in diabetics are scanty and contradictory. The aim of our study was to assess the prevalence of H. pylori infection in diabetic patients and to evaluate the association between endoscopic features and H. pylori colonization of the gastric mucosa in diabetes mellitus. Methods: A cross-sectional study of 172 dyspeptic patients (67 diabetics and 105 nondiabetic subjects) was designed. In all cases, an upper gastrointestinal endoscopy was performed, gastroduodenal lesions were noted, and the presence of gastritis and H. pylori was assessed by histopathological examination. Differences between diabetic patients and nondiabetic subjects were evaluated. Results: The difference of H. pylori prevalence between diabetics (37.3%) and nondiabetics (35.2%) was not significant (P50.78). Nor did the prevalence of gastritis and peptic ulcer differ significantly between the two groups (59.7% vs. 49.5%, P50.19; and 32.8% vs. 40.9%, P50.08, respectively). Studying only H. pylori-positive patients, we found no difference between diabetics and nondiabetics with regard to the prevalence of either gastritis (80% vs. 72.9%, P50.71) or peptic ulcer (91.8% vs. 76%, P50.09). Conclusions: Our data do not support an association between H. pylori infection and diabetes mellitus. This is confirmed by the lack of difference between diabetics and nondiabetics with regard to the prevalence of both H. pylori infection and H. pylori-related gastroduodenal disorders. 2002 Elsevier Science B.V. All rights reserved. Keywords: Diabetes mellitus; Helicobacter pylori; Prevalence
1. Introduction Helicobacter pylori (H. pylori) infection affects approximately 50% of the world’s population [1]. It seems to be the primary cause of chronic antral gastritis [2] and is strongly associated with peptic ulcer disease [3], gastric cancer [4], and gastric MALT-lymphoma [5]. From this
*Corresponding author. 20 Ierosolimon St., P.O. 112 52, Athens, Greece. E-mail address: [email protected] (R. Anastasios).
aspect, identification of risk groups is increasingly important. It is well known that infections in diabetic patients occur frequently and tend to be severe, due to the impairment of the immune status [6]. It has also been suggested that delayed gastric emptying (gastroparesis diabeticorum) may lead to bacterial overgrowth in the upper gastrointestinal tract [7,8]. However, data on the prevalence of H. pylori infection in diabetics are scanty and contradictory. The prevalence of H. pylori infection has been variously reported as high [7–10], low [11], and normal [12–14]. Thus, the significance of diabetes mellitus as a risk factor
0953-6205 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. PII: S0953-6205( 02 )00094-8
R. Anastasios et al. / European Journal of Internal Medicine 13 (2002) 376–379
for H. pylori gastric colonization remains unknown. Moreover, insufficient information is available regarding the correlation between H. pylori infection and endoscopically proven gastroduodenal lesions in diabetes mellitus. The aim of this cross-sectional endoscopic study was to assess the prevalence of H. pylori infection in diabetes mellitus and to study the relationship between endoscopic features and H. pylori infection in diabetic patients.
2. Materials and methods The study involved 235 dyspeptic patients referred to our department for upper gastrointestinal endoscopy between June 1998 and September 2000. Dyspepsia was defined, according to the Rome criteria, as persistent or recurrent pain or discomfort centered in the upper abdomen or epigastrium [15]. The local ethics committee approved the study, and signed informed consent was obtained from each participant. All subjects were interviewed, by means of a structured questionnaire, to obtain general demographic details and to gather information regarding recent use of antisecretory drugs and history of diabetes. Moreover, fasting plasma glucose (FPG) was checked in all subjects. Fasting was defined as no caloric intake for at least 8 h. According to the diagnostic criteria of diabetes mellitus as defined by the American Diabetes Association, only patients with a FPG above 126 mg / dl were considered as diabetics [16]. Each diabetic patient was then asked about the duration of his / her diabetes and the use of oral antidiabetic agents or insulin. All patients underwent routine upper endoscopy performed by one of the authors. The presence of lesions in the gastroduodenal mucosa was noted. A patient was included in the ulcer group if one of the following lesions was noted: (1) a circumscribed break of the mucosa with apparent depth covered by an exudate, (2) a healing ulcer, or (3) an ulcer scarring. Moreover, in each patient two biopsy specimens were obtained from the antrum and the corpus (both the anterior and posterior wall of each). The specimens were stained with hematoxylin–eosin, Alcian blue (pH 2.5), periodic acid–Schiff and, for the presence of H. pylori, modified Giemsa stains. The presence of gastritis was assessed by histopathological examination, in accordance with the recommendations of the working party that developed the Sydney System [17]. A single pathologist, who was blind to the endoscopic findings and symptoms of the patient, read the histology slides. Finally, we excluded 63 patients from the analysis. Exclusion criteria were: (1) age ,18 years, (2) prior Helicobacter eradication therapy, (3) use of antisecretory drugs or antibiotics in the preceding 6 months, (4) a history of vagotomy or operations on the upper gastrointestinal tract, (5) endoscopic diagnosis of gastric cancer proven by histopathological examination, and (6) use of
377
nonsteroidal anti-inflammatory drugs. Therefore, 172 patients were eligible for analysis.
2.1. Statistical analysis Results are expressed as the mean6one standard deviation (6S.D.). A chi-squared ( x 2 ) test with Yate’s correction was used to detect differences between groups and predictive indices. x 2 analysis was performed using the SPSS program (SPSS, IL, USA). P,0.05 was considered statistically significant.
3. Results Of the 172 patients aged 59.2612.3 years who were eligible for analysis, 99 were men (age 58.8612.7 years) and 73 were women (age 59.7611.9 years); the male / female ratio was 1.3. A total of 67 patients (39 men and 28 women aged 61.4612.3 years) were diabetics. Of these patients, 64 (95.5%) had reported a history of diabetes and three patients (4.5%) were newly diagnosed. Patients who reported a history of diabetes had been treated with insulin (18 patients, 28.1%), oral antidiabetic agents (30 patients, 46.9%), a combination of insulin and oral antidiabetic agents (10 patients, 15.6%), or diet alone (six patients, 9.4%). The remaining 105 subjects (60 men and 45 women aged 58.8613.3 years) were nondiabetics. Gender and mean age did not differ significantly between the two groups (diabetics vs. nondiabetics). The prevalence of gastroduodenal lesions (gastritis and / or peptic ulcer) in both groups is shown in Table 1. The prevalence of gastritis did not differ significantly between the two groups (P50.71) The prevalence of peptic ulcer was higher in nondiabetic subjects, but the difference was also not significant (P50.08). H. pylori infection was detected in 37.3% of diabetics and in 35.2% of nondiabetic subjects (Table 2). The difference in H. pylori prevalence between the two groups was not statistically significant (P50.78). Moreover, no significant difference was found between infected and uninfected diabetic patients with regard to the duration of diabetes (12.169.2 and 11.969.0 years, respectively, P50.82). H. pylori infection was detected in 20 / 40 diabetics (40%) with gastritis and in 19 / 22 diabetics (86.3%) with peptic ulcer. Some 27 / 52 nondiabetics (51.9%) with gastritis and 34 / 40 nondiabetics (85%) with peptic ulcer Table 1 Prevalence of gastroduodenal lesions in the study populations. The results are also expressed as percentages of the total number of patients in each group (diabetics or nondiabetics)
Gastritis Peptic ulcer
Diabetics N (%)
Nondiabetics N (%)
P
40 (59.7) 22 (32.8)
52 (49.5) 43 (40.9)
0.19 0.08
R. Anastasios et al. / European Journal of Internal Medicine 13 (2002) 376–379
378 Table 2 Prevalence of H. pylori infection
Diabetics Nondiabetics Total
H. pylori-positive N (%)
H. pylori-negative N (%)
Total N (%)
25 (37.3) 37 (35.2) 62 (36)
42 (62.7) 68 (64.8) 110 (64)
67 (100) 105 (100) 172 (100)
Difference in H. pylori prevalence: statistically not significant (P5 0.78).
were also infected with H. pylori. Table 3 summarizes the distribution of gastroduodenal disorders among H. pyloriinfected patients (H. pylori 1). The difference in prevalence of gastritis between H. pylori 1 diabetics and H. pylori 1 nondiabetics was not statistically significant (P5 0.71). Finally, although peptic ulcer prevalence was higher in H. pylori 1 nondiabetics, the difference was also not significant (P50.09).
4. Discussion The published data concerning the association between H. pylori infection and diabetes mellitus are few and contradictory. There have been reports based on serologic antibody confirmation claiming a high prevalence of H. pylori infection among diabetic patients [7–10]. In contrast, based on histological evidence, Malecki et al. [11] showed that H. pylori infection plays a minor role in upper gastrointestinal tract disorders in diabetics. Finally, in three recent studies, no independent association between diabetes mellitus and H. pylori infection was found [12–14]. In the eight previous studies, the reported prevalence of H. pylori infection in diabetics ranged from 30 to 78%. The variability of prevalence rates may be related to the epidemiological distribution of H. pylori or to different inclusion criteria for patient enrollment. We examined a large number of dyspeptic patients referred to our department for upper gastrointestinal endoscopy for H. pylori infection. Dyspeptic symptoms are known to be common in individuals with diabetes [18,19] and this could explain the high proportion of diabetics (38%) in our study population. We used mucosal biopsy and histological examination of the specimen. Although the ideal method for diagnosis of H. pylori infection is a point of debate, histological examination is generally considered to be a reliable method for detection of H. Table 3 Distribution of gastroduodenal lesions among H. pylori 1 subjects. The results are also expressed as percentages of the total number of H. pylori 1 patients in each group (diabetics or nondiabetics)
Gastritis Peptic ulcer
Diabetics N (%)
Nondiabetics N (%)
P
20 (80) 19 (76)
27 (72.9) 34 (91.8)
0.71 0.09
pylori [20]. Our results are in line with recent observations [12–14]. No association was detected between H. pylori infection and diabetes mellitus. Moreover, the observed lack of difference between infected and uninfected diabetics with regard to the duration of diabetes further supports the hypothesis that diabetes mellitus may not be a predisposing condition for H. pylori colonization of the gastric mucosa. Diabetics are known to be susceptible to chronic infection, due to the impairment of their immune status. The delayed gastric emptying (gastroparesis diabeticorum) and the alterations in gastric mucosa in diabetes mellitus may also lead to bacterial overgrowth in the upper gastrointestinal tract [7,8,21]. However, we did not check for the presence of bacterial overgrowth in biopsy specimens. As far as we know, there are no data in the literature concerning an association of possible non-H. pylori flora existing in the diabetic stomach and an increased likelihood of H. pylori colonization. Moreover, it is unclear whether immunocompromised patients are at a high risk for H. pylori infection. In contrast, previous studies in immunocompromised patients with acquired immunodeficiency syndrome have shown that an inadequate cellular immune response might impair H. pylori colonization and its sustained infection [22–24]. Moreover, the diminished secretion of hydrochloric acid, which occurs in a high percentage of diabetic patients (diabetes-induced achlorydria), is harmful to H. pylori [25–27]. Therefore, it seems that the prevalence of H. pylori infection in diabetes mellitus reflects an intricate balance between possible predisposing conditions (e.g. gastroparesis diabeticorum) and preventing factors (e.g. diabetes-induced achlorydria). It is certain that many other factors related to H. pylori colonization of gastric mucosa in diabetes mellitus still remain unknown. In our study, diabetics had a higher incidence of gastritis and a lower incidence of peptic ulcer than nondiabetic subjects, although the differences were not significant. These results are consistent with previous studies in larger populations of diabetics and can be attributed to the diabetes-induced achlorydria [24,28,29]. Although there are many reports on the seroprevalence of H. pylori in diabetics, the relationship between H. pylori infection and the gastroduodenal lesions (gastritis and peptic ulcer) in diabetes mellitus remains poorly investigated. In our study, no difference in the prevalence of gastroduodenal lesions between H. pylori 1 diabetics and H. pylori 1 nondiabetics was detected. Although diabetics might be expected to be more susceptible to the harmful effects of H. pylori due to their impaired immune status, our results showed that diabetics infected with H. pylori are not at an increased risk for gastroduodenal lesions. We cannot rule out the possibility that other, more complicated, factors affect the natural history of H. pylori infection in diabetic patients. It is already known that the gastroduodenal lesions caused in the general population by H. pylori infection are the end result of several factors,
R. Anastasios et al. / European Journal of Internal Medicine 13 (2002) 376–379
including the direct effects of H. pylori on gastric mucosa, autoimmune mechanisms, and crossreaction of H. pylori antibodies with human gastric mucosa [30–33]. Our endoscopic study could not show how diabetes mellitus influences these different pathways. Moreover, we did not focus on the severity of diabetes and we have no data regarding systemic complications of the disease in our sample. This might be considered as a disadvantage of our study. Further studies should be undertaken to evaluate the association between the severity of diabetes and H. pylorirelated gastroduodenal lesions in diabetics. In conclusion, our results do not support an association between H. pylori infection and diabetes mellitus. This is confirmed by the lack of difference between diabetics and nondiabetics with regard to the prevalence of both H. pylori infection and H. pylori-related gastroduodenal lesions.
References [1] Megraud F. Epidemiology of H. pylori infection. Gastroenterol Clin North Am 1993;22:73–88. [2] Sipponen P, Hyvarinen H. Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer. Scand J Gastroenterol 1993;28(Suppl 196):3–6. [3] Labenz J, Borsch G. Evidence for the essential role of Helicobacter pylori in gastric ulcer disease. Gut 1994;35:19–22. [4] Eslick GD, Lim LL-Y, Byles JE, Xia HH, Taley NJ. Association of Helicobacter pylori infection with gastric carcinoma: a meta-analysis. Am J Gastroenterol 1999;94:2373–9. [5] Parsonet J, Hansen S, Rodriguez L et al. Helicobacter pylori and gastric lymphoma. New Engl J Med 1994;330:1267–71. [6] Unger RH, Foster DW. Diabetes mellitus. In: Wilson JD, Foster DW, editors, Williams’ textbook of endocrinology, 8th ed., Philadelphia: Saunders, 1992, pp. 1255–333. [7] Perdichizzi G, Bottari M, Pallio S, Fera MT, Carbone M, Barresi G. Gastric infection by Helicobacter pylori and antral gastritis in hyperglycemic obese and in diabetic subjects. New Microbiol 1996;19(2):149–54. [8] Gentile S, Turco S, Oliviero B, Torella R. The role of autonomic neuropathy as a risk factor of Helicobacter pylori infection in dyspeptic patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 1998;42(1):41–8. [9] Gasbarrini A, Ojetti V, Pitocco D et al. Helicobacter pylori infection in patients affected by insulin-dependent diabetes mellitus. Eur J Gastroenterol Hepatol 1998;10(6):469–72. [10] Oldensbury B, Diepersloot RJA, Hoekstra JBL. High seroprevalence of Helicobacter pylori in diabetes mellitus patients. Dig Dis Sci 1996;41:458–61. [11] Malecki M, Bien AI, Galicka-Latala D, Stachura J, Sieradzki I. The prevalence of Helicobacter pylori infection and types of gastritis in diabetic patients. The Krakow study. Exp Clin Endocrinol Diabetes 1996;104:365–9. [12] Woodward M, Morrison C, Mccoll K. An investigation into factors associated with Helicobacter pylori infection. J Clin Epidemiol 2000;53:175–81.
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[13] Rosenstock SJ, Jorgensen T, Andersen LP, Bonnevic O. Association of Helicobacter pylori infection with lifestyle, chronic diseases, body-indices and age at menarche in Danish adults. Scand J Public Health 2000;28(1):32–40. [14] Hia HH, Talley NJ, Kam EP, 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(4):1039–46. [15] Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR, Tytgat GN. Functional gastroduodenal disorders. Gut 1999;45(Suppl 2):37–42. [16] Report of the Expert Committee on the Diagnosis and Treatment of Diabetes Mellitus. Diabetes Care 1997;20(7):1183–87. [17] Price AB. The Sydney system: histological division. J Gastroenterol Hepatol 1991;6:109–22. [18] Bytzer MP, Talley NJ, Leemon M et al. Diabetes mellitus is associated with an increased prevalence of gastrointestinal symptoms: results from a population-based survey of 15,000 adults. Gastroenterology 2000;118:A176, abstract. [19] Ricci JA, Siddique R, Stewart WF, Sandler RS, Sloan S, Farup CE. Upper gastrointestinal symptoms in a U.S. national sample of adults with diabetes. Scand J Gastroenterol 2000;35:152–9. [20] Peterson W, Graham D. Helicobacter pylori. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors, Sleisenger and Fortdran’s gastrointestinal and liver disease, 1998, pp. 604–19. [21] Gunever R, Akcan Y, Paksoy I, Soulu AR, Aydin M, Arslan S. Helicobacter pylori associated gastric pathology in patients with type II diabetes mellitus and its relationship with gastric emptying. Ankara Study. Exp Clin Endocrinol Diabetes 1999;107(3):172–6. [22] Francis ND, Logan RP, Walker MM et al. Campylobacter pylori in the upper gastrointestinal tract of patients with HIV-1 infection. J Clin Pathol 1990;43:60–2. [23] Battan R, Raviglione MC, Palagiano A et al. Helicobacter pylori infection in patients with acquired immune deficiency syndrome. Am J Gastroenterol 1990;85:1576–9. [24] Marano BJ, Smith F, Bonanno CA. Helicobacter pylori infection in patients with acquired immunodeficiency syndrome. Am J Gastroenterol 1993;88:687–90. [25] Cogal RK, Spiro HM. Gastrointestinal manifestations of diabetes mellitus. Med Clin North Am 1971;55:1031–44. [26] Clyne M, Labigne A, Drumm B. Helicobacter pylori requires an acidic environment to survive in the presence of urea. Infect Immun 1995;63:1669–73. [27] McGowann CC, Cover TL, Blaser MJ. Helicobacter pylori and gastric acid: biologic and therapeutic implications. Gastroenterology 1996;110:926–38. [28] Wood MN. Chronic peptic ulcer in ninety-four diabetics. Am J Dig Dis 1947;14:1–11. [29] Dotevall G. Incidence of peptic ulcer in diabetes mellitus. Acta Med Scand 1959;164:463–77. [30] Yoshida N, Granger D, Evans DJ, Evans DG, Graham DY, Kvietys P. Mechanisms involved in Helicobacter pylori inflammation. Gastroenterology 1993;105:1432–40. [31] Growe SE, Alvarez L, Dytoc M et al. Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vivo. Gastroenterology 1995;108(1):65–74. [32] Grabtree JE. Gastric mucosal inflammatory responses to Helicobacter pylori. Aliment Pharmacol Ther 1996;10(Suppl 1):29–37. [33] Negrini R, Lisato L, Cavazzini L et al. Helicobacter pylori infection induces antibodies cross-reacting with human gastric mucosa. Gastroenterology 1991;101(2):437–45.
Original article
Helicobacter pylori infection in diabetic patients: prevalence and endoscopic findings a, a b c Roussos Anastasios *, Constantin Goritsas , Christos Papamihail , Rodoula Trigidou , b a Peter Garzonis , Angeliki Ferti a
Department of Internal Medicine, General Regional Hospital ‘ Sotiria’, Athens, Greece b Endoscopy Department, General Regional Hospital ‘ Sotiria’, Athens, Greece c Department of Pathology, General Regional Hospital ‘ Sotiria’, Athens, Greece
Received 28 August 2001; received in revised form 13 November 2001; accepted 15 November 2001
Abstract Background: In patients with diabetes mellitus, chronic infections are frequent and severe, due to the impairment of their immune status. However, data on the prevalence of Helicobacter pylori (H. pylori) infection in diabetics are scanty and contradictory. The aim of our study was to assess the prevalence of H. pylori infection in diabetic patients and to evaluate the association between endoscopic features and H. pylori colonization of the gastric mucosa in diabetes mellitus. Methods: A cross-sectional study of 172 dyspeptic patients (67 diabetics and 105 nondiabetic subjects) was designed. In all cases, an upper gastrointestinal endoscopy was performed, gastroduodenal lesions were noted, and the presence of gastritis and H. pylori was assessed by histopathological examination. Differences between diabetic patients and nondiabetic subjects were evaluated. Results: The difference of H. pylori prevalence between diabetics (37.3%) and nondiabetics (35.2%) was not significant (P50.78). Nor did the prevalence of gastritis and peptic ulcer differ significantly between the two groups (59.7% vs. 49.5%, P50.19; and 32.8% vs. 40.9%, P50.08, respectively). Studying only H. pylori-positive patients, we found no difference between diabetics and nondiabetics with regard to the prevalence of either gastritis (80% vs. 72.9%, P50.71) or peptic ulcer (91.8% vs. 76%, P50.09). Conclusions: Our data do not support an association between H. pylori infection and diabetes mellitus. This is confirmed by the lack of difference between diabetics and nondiabetics with regard to the prevalence of both H. pylori infection and H. pylori-related gastroduodenal disorders. 2002 Elsevier Science B.V. All rights reserved. Keywords: Diabetes mellitus; Helicobacter pylori; Prevalence
1. Introduction Helicobacter pylori (H. pylori) infection affects approximately 50% of the world’s population [1]. It seems to be the primary cause of chronic antral gastritis [2] and is strongly associated with peptic ulcer disease [3], gastric cancer [4], and gastric MALT-lymphoma [5]. From this
*Corresponding author. 20 Ierosolimon St., P.O. 112 52, Athens, Greece. E-mail address: [email protected] (R. Anastasios).
aspect, identification of risk groups is increasingly important. It is well known that infections in diabetic patients occur frequently and tend to be severe, due to the impairment of the immune status [6]. It has also been suggested that delayed gastric emptying (gastroparesis diabeticorum) may lead to bacterial overgrowth in the upper gastrointestinal tract [7,8]. However, data on the prevalence of H. pylori infection in diabetics are scanty and contradictory. The prevalence of H. pylori infection has been variously reported as high [7–10], low [11], and normal [12–14]. Thus, the significance of diabetes mellitus as a risk factor
0953-6205 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. PII: S0953-6205( 02 )00094-8
R. Anastasios et al. / European Journal of Internal Medicine 13 (2002) 376–379
for H. pylori gastric colonization remains unknown. Moreover, insufficient information is available regarding the correlation between H. pylori infection and endoscopically proven gastroduodenal lesions in diabetes mellitus. The aim of this cross-sectional endoscopic study was to assess the prevalence of H. pylori infection in diabetes mellitus and to study the relationship between endoscopic features and H. pylori infection in diabetic patients.
2. Materials and methods The study involved 235 dyspeptic patients referred to our department for upper gastrointestinal endoscopy between June 1998 and September 2000. Dyspepsia was defined, according to the Rome criteria, as persistent or recurrent pain or discomfort centered in the upper abdomen or epigastrium [15]. The local ethics committee approved the study, and signed informed consent was obtained from each participant. All subjects were interviewed, by means of a structured questionnaire, to obtain general demographic details and to gather information regarding recent use of antisecretory drugs and history of diabetes. Moreover, fasting plasma glucose (FPG) was checked in all subjects. Fasting was defined as no caloric intake for at least 8 h. According to the diagnostic criteria of diabetes mellitus as defined by the American Diabetes Association, only patients with a FPG above 126 mg / dl were considered as diabetics [16]. Each diabetic patient was then asked about the duration of his / her diabetes and the use of oral antidiabetic agents or insulin. All patients underwent routine upper endoscopy performed by one of the authors. The presence of lesions in the gastroduodenal mucosa was noted. A patient was included in the ulcer group if one of the following lesions was noted: (1) a circumscribed break of the mucosa with apparent depth covered by an exudate, (2) a healing ulcer, or (3) an ulcer scarring. Moreover, in each patient two biopsy specimens were obtained from the antrum and the corpus (both the anterior and posterior wall of each). The specimens were stained with hematoxylin–eosin, Alcian blue (pH 2.5), periodic acid–Schiff and, for the presence of H. pylori, modified Giemsa stains. The presence of gastritis was assessed by histopathological examination, in accordance with the recommendations of the working party that developed the Sydney System [17]. A single pathologist, who was blind to the endoscopic findings and symptoms of the patient, read the histology slides. Finally, we excluded 63 patients from the analysis. Exclusion criteria were: (1) age ,18 years, (2) prior Helicobacter eradication therapy, (3) use of antisecretory drugs or antibiotics in the preceding 6 months, (4) a history of vagotomy or operations on the upper gastrointestinal tract, (5) endoscopic diagnosis of gastric cancer proven by histopathological examination, and (6) use of
377
nonsteroidal anti-inflammatory drugs. Therefore, 172 patients were eligible for analysis.
2.1. Statistical analysis Results are expressed as the mean6one standard deviation (6S.D.). A chi-squared ( x 2 ) test with Yate’s correction was used to detect differences between groups and predictive indices. x 2 analysis was performed using the SPSS program (SPSS, IL, USA). P,0.05 was considered statistically significant.
3. Results Of the 172 patients aged 59.2612.3 years who were eligible for analysis, 99 were men (age 58.8612.7 years) and 73 were women (age 59.7611.9 years); the male / female ratio was 1.3. A total of 67 patients (39 men and 28 women aged 61.4612.3 years) were diabetics. Of these patients, 64 (95.5%) had reported a history of diabetes and three patients (4.5%) were newly diagnosed. Patients who reported a history of diabetes had been treated with insulin (18 patients, 28.1%), oral antidiabetic agents (30 patients, 46.9%), a combination of insulin and oral antidiabetic agents (10 patients, 15.6%), or diet alone (six patients, 9.4%). The remaining 105 subjects (60 men and 45 women aged 58.8613.3 years) were nondiabetics. Gender and mean age did not differ significantly between the two groups (diabetics vs. nondiabetics). The prevalence of gastroduodenal lesions (gastritis and / or peptic ulcer) in both groups is shown in Table 1. The prevalence of gastritis did not differ significantly between the two groups (P50.71) The prevalence of peptic ulcer was higher in nondiabetic subjects, but the difference was also not significant (P50.08). H. pylori infection was detected in 37.3% of diabetics and in 35.2% of nondiabetic subjects (Table 2). The difference in H. pylori prevalence between the two groups was not statistically significant (P50.78). Moreover, no significant difference was found between infected and uninfected diabetic patients with regard to the duration of diabetes (12.169.2 and 11.969.0 years, respectively, P50.82). H. pylori infection was detected in 20 / 40 diabetics (40%) with gastritis and in 19 / 22 diabetics (86.3%) with peptic ulcer. Some 27 / 52 nondiabetics (51.9%) with gastritis and 34 / 40 nondiabetics (85%) with peptic ulcer Table 1 Prevalence of gastroduodenal lesions in the study populations. The results are also expressed as percentages of the total number of patients in each group (diabetics or nondiabetics)
Gastritis Peptic ulcer
Diabetics N (%)
Nondiabetics N (%)
P
40 (59.7) 22 (32.8)
52 (49.5) 43 (40.9)
0.19 0.08
R. Anastasios et al. / European Journal of Internal Medicine 13 (2002) 376–379
378 Table 2 Prevalence of H. pylori infection
Diabetics Nondiabetics Total
H. pylori-positive N (%)
H. pylori-negative N (%)
Total N (%)
25 (37.3) 37 (35.2) 62 (36)
42 (62.7) 68 (64.8) 110 (64)
67 (100) 105 (100) 172 (100)
Difference in H. pylori prevalence: statistically not significant (P5 0.78).
were also infected with H. pylori. Table 3 summarizes the distribution of gastroduodenal disorders among H. pyloriinfected patients (H. pylori 1). The difference in prevalence of gastritis between H. pylori 1 diabetics and H. pylori 1 nondiabetics was not statistically significant (P5 0.71). Finally, although peptic ulcer prevalence was higher in H. pylori 1 nondiabetics, the difference was also not significant (P50.09).
4. Discussion The published data concerning the association between H. pylori infection and diabetes mellitus are few and contradictory. There have been reports based on serologic antibody confirmation claiming a high prevalence of H. pylori infection among diabetic patients [7–10]. In contrast, based on histological evidence, Malecki et al. [11] showed that H. pylori infection plays a minor role in upper gastrointestinal tract disorders in diabetics. Finally, in three recent studies, no independent association between diabetes mellitus and H. pylori infection was found [12–14]. In the eight previous studies, the reported prevalence of H. pylori infection in diabetics ranged from 30 to 78%. The variability of prevalence rates may be related to the epidemiological distribution of H. pylori or to different inclusion criteria for patient enrollment. We examined a large number of dyspeptic patients referred to our department for upper gastrointestinal endoscopy for H. pylori infection. Dyspeptic symptoms are known to be common in individuals with diabetes [18,19] and this could explain the high proportion of diabetics (38%) in our study population. We used mucosal biopsy and histological examination of the specimen. Although the ideal method for diagnosis of H. pylori infection is a point of debate, histological examination is generally considered to be a reliable method for detection of H. Table 3 Distribution of gastroduodenal lesions among H. pylori 1 subjects. The results are also expressed as percentages of the total number of H. pylori 1 patients in each group (diabetics or nondiabetics)
Gastritis Peptic ulcer
Diabetics N (%)
Nondiabetics N (%)
P
20 (80) 19 (76)
27 (72.9) 34 (91.8)
0.71 0.09
pylori [20]. Our results are in line with recent observations [12–14]. No association was detected between H. pylori infection and diabetes mellitus. Moreover, the observed lack of difference between infected and uninfected diabetics with regard to the duration of diabetes further supports the hypothesis that diabetes mellitus may not be a predisposing condition for H. pylori colonization of the gastric mucosa. Diabetics are known to be susceptible to chronic infection, due to the impairment of their immune status. The delayed gastric emptying (gastroparesis diabeticorum) and the alterations in gastric mucosa in diabetes mellitus may also lead to bacterial overgrowth in the upper gastrointestinal tract [7,8,21]. However, we did not check for the presence of bacterial overgrowth in biopsy specimens. As far as we know, there are no data in the literature concerning an association of possible non-H. pylori flora existing in the diabetic stomach and an increased likelihood of H. pylori colonization. Moreover, it is unclear whether immunocompromised patients are at a high risk for H. pylori infection. In contrast, previous studies in immunocompromised patients with acquired immunodeficiency syndrome have shown that an inadequate cellular immune response might impair H. pylori colonization and its sustained infection [22–24]. Moreover, the diminished secretion of hydrochloric acid, which occurs in a high percentage of diabetic patients (diabetes-induced achlorydria), is harmful to H. pylori [25–27]. Therefore, it seems that the prevalence of H. pylori infection in diabetes mellitus reflects an intricate balance between possible predisposing conditions (e.g. gastroparesis diabeticorum) and preventing factors (e.g. diabetes-induced achlorydria). It is certain that many other factors related to H. pylori colonization of gastric mucosa in diabetes mellitus still remain unknown. In our study, diabetics had a higher incidence of gastritis and a lower incidence of peptic ulcer than nondiabetic subjects, although the differences were not significant. These results are consistent with previous studies in larger populations of diabetics and can be attributed to the diabetes-induced achlorydria [24,28,29]. Although there are many reports on the seroprevalence of H. pylori in diabetics, the relationship between H. pylori infection and the gastroduodenal lesions (gastritis and peptic ulcer) in diabetes mellitus remains poorly investigated. In our study, no difference in the prevalence of gastroduodenal lesions between H. pylori 1 diabetics and H. pylori 1 nondiabetics was detected. Although diabetics might be expected to be more susceptible to the harmful effects of H. pylori due to their impaired immune status, our results showed that diabetics infected with H. pylori are not at an increased risk for gastroduodenal lesions. We cannot rule out the possibility that other, more complicated, factors affect the natural history of H. pylori infection in diabetic patients. It is already known that the gastroduodenal lesions caused in the general population by H. pylori infection are the end result of several factors,
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including the direct effects of H. pylori on gastric mucosa, autoimmune mechanisms, and crossreaction of H. pylori antibodies with human gastric mucosa [30–33]. Our endoscopic study could not show how diabetes mellitus influences these different pathways. Moreover, we did not focus on the severity of diabetes and we have no data regarding systemic complications of the disease in our sample. This might be considered as a disadvantage of our study. Further studies should be undertaken to evaluate the association between the severity of diabetes and H. pylorirelated gastroduodenal lesions in diabetics. In conclusion, our results do not support an association between H. pylori infection and diabetes mellitus. This is confirmed by the lack of difference between diabetics and nondiabetics with regard to the prevalence of both H. pylori infection and H. pylori-related gastroduodenal lesions.
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