The Role of Helicobacter Pylori Infection on Atherosclerosis in Diabetic Patients


 Background: In this study, the aim was to investigate the effect of Helicobacter pylori (Hp) presence on intima-media thickness, which is an early sign of atherosclerosis in type 2 diabetic patients.Methods: This study is a retrospective study conducted with type 2 diabetic patients who were followed up in the gastroenterology and diabetes outpatient clinic. The relationship between the presence of Hp and laboratory findings, demographic and clinical characteristics, intima-media thickness and pathology findings were analyzed in patients who underwent endoscopy for dyspepsia.Results: A total of 73 cases meeting the exclusion criteria, 32 males (43.8%) and 41 females (56.2%), between 42 and 83 years with an average age of 59 ± 10 years were included in the study. Of the cases, 31 (42.4%) were found to be Hp positive. The presence of Hp and accompanying diseases, drug treatments used, demographic characteristics, biochemical parameters, endoscopy and pathology results, and intima-media thicknesses were compared. ALT value was found to be higher in Hp negative cases (p<0.005). The presence of Hp was found to increase the carotid intima-media thickness by 0.092 units (p: 0.018) at 95% significance level on the left and 0.060 units at 90% significance level on the right (p: 0.063). There was no significant difference for other variables.Conclusion: It was shown that the presence of Hp increases the carotid intima-media thickness in patients with type 2 diabetes. Similarly, LDL and age were shown to have an increasing effect on intima-media thickness.


Introduction
Diabetes mellitus (DM) is a metabolism disease resulting from insulin de ciency or reduced insulin effect [1].
Among chronic complications, coronary artery disease (CAD) is the most important cause of mortality and morbidity in diabetic patients [2]. Type 2 diabetics have 2-4 times higher risk of CAD than the normal population and most die due to macrovascular events [3]. Atherosclerosis is a chronic in ammatory process characterized by thickening and stiffening of vein walls and causes diseases with high morbidity like myocardial infarction and stroke [4,5].
Diabetes, hypertension and hyperlipidemia disrupt the endothelial integrity of veins and begin this in ammatory process [4]. Atherosclerosis begins to form at early ages in diabetics and more widespread involvement occurs [1].
It is thought that chronic in ammation and disruption of the venous structure occurring with Helicobacter pylori (Hp) infection forms a risk for atherosclerosis [6]. Carotid intima media thickness (CIMT) is accepted as a noninvasive and good marker of early atherosclerotic changes [7]. In this study, CIMT measurements were used with the aim of researching the effect on atherosclerosis of Hp infection in diabetic patients.

Material And Method
Our retrospective study included type 2 diabetes patients aged 18 years and older attending the gastroenterology and diabetic clinics with gastroscopy performed for dyspeptic complaints and carotid Doppler examination.
Clinical records of patients were assessed; those younger than 18 years, pregnant cases, with Hp eradication performed, with DM diagnosis other than type 2 DM and with cardiovascular, cerebrovascular or peripheral artery Page 3/12 disease were excluded from the study. Patient age, gender, body mass index (BMI), smoking habit, duration of diabetes, comorbid chronic diseases and medications used were recorded.
Blood samples were taken after 8-hours fasting. Complete blood count levels were measured using an automatic hematology analyzer (Beckman Coulter, Brea, CA, USA). Serum glucose measurements were identi ed using the enzymatic route with the hexokinase method (Roche Diagnostics GmbH, Mannheim, Germany). HbA1c levels were measured with a COBAS 311 analyzer using the particle-supported immunoturbidometric method (Roche Diagnostics GmbH, Mannheim, Germany). HbA1c results are stated as percentage of total Hb in accordance with the Diabetes Control and Complication Trial/ National Glycohemoglobin Standardization Program (DCCT/NGSP).
The gastroscopy procedure was performed with a Fujinon endoscopy device by a single gastroenterologist.
Endoscopy results were categorized as gastritis, ulcer, hernia and esophagitis. The presence of Hp was researched with endoscopic biopsy and pathological assessment used the Sydney protocol; with in ammation, atrophy,

Results
As shown in Table 1, there were no statistically signi cant differences between the age, DM duration, BMI, gender and smoking habit of cases according to the presence of Hp (p>0.05). According to the presence of Hp, cases were not identi ed to have statistically signi cant differences in fasting blood sugar, HbA1c, total cholesterol, triglycerides, HDL, LDL, non-HDL, Hb, albumin/creatinine, GFR and CRP measurements (p>0.05) ( Table 2). As shown in Table 3, 31.5% of cases (n=23) were smokers, while 42.5% (n=31) were Hp positive.     [14].
There are many studies researching the relationship between Hp and lipid pro le in the literature. A study by Rahman et al. compared lipid pro les between Hp positive cases with and without CAD and identi ed no signi cant changes in total cholesterol, triglyceride and LDL cholesterol values, but HDL cholesterol was low in both groups [20]. A study by Laurila et al. [21] found similar results with high total cholesterol and triglyceride values and similar HDL cholesterol values in Hp positive cases compared to negative cases. Another study [22] showed lower HDL cholesterol value in Hp positive cases compared to negative ones. A different study identi ed LDL cholesterol values were high in Hp positive individuals [23]. Vafaeimanesh et al. [24] found no signi cant difference in lipid parameters in Hp positive or negative cases, similar to our study. This result may be linked to the low number of participants in the study and patients who attended regular clinical follow-up beginning lipidlowering treatment in the early period. There are studies showing a relationship between microalbuminuria, an early clinical marker of diabetic nephropathy, with endothelial dysfunction and subclinical atherosclerosis [27,28]. A study by Chung et al. identi ed that Hp positivity was independently associated with the presence of microalbuminuria and urine albumin creatinine ratio had positive correlation with severity [29]. In our study, we showed the presence of Hp had no signi cant effect on albumin creatinine ratio and GFR level. Different from these studies, this result may be linked to the Hp positive and negative cases included in the study having similar risk factors for microvascular complications. In the study, Hp positive and negative cases did not have signi cant differences between diabetic duration and RAS blocker use so the actual effect on albumin creatinine ratio and GFR level may be inferred to be RAS blocker use and diabetic duration, rather than Hp.
The in ammation parameter of CRP was shown to increase CAD risk in many studies [30,31] [24].
There are studies showing Hp positivity in adults is positively correlated with disrupted glucose tolerance [33,34].
In this context, the study by Chen et al. [35] [41]. In our study, Hp positivity did not have a signi cant effect on plaque formation. This result leads to consideration that the basis of plaque formation in the carotid artery is not the presence of Hp, but is associated with the elevation in HbA1c. In fact, patients with increased plaque formation in the carotid artery were reported to differentiate not just in terms of the presence of Hp but also in terms of HbA1c elevation in the study by Hu et al. [41]. In our study, the reason for the lack of observation of a signi cant correlation between Hp presence and carotid artery plaque formation may be the similar HbA1c levels in both groups.
Limitations of our study include the lack of prospective study and the low number of patients. However, strong aspects of our study include research of the presence of Hp with endoscopic methods and detailed knowledge of medications used by participants.

Conclusion
In our study, Hp infection in type 2 diabetes patients with similar risk factors for atherosclerosis was independently shown to increase CIMT. This result leads to consideration that eradication of Hp in patients with atherosclerosis risk factors may reduce the atherosclerosis progression. Assessment of CIMT after Hp eradication in a prospective study of groups with similar characteristics will assist in answering this question.

Declerations
Ethics approval and consent to participate: The research was completed with permission from the Clinical Research Ethics Committee dated 27.10.2020 decision number 2020/514/188/4.
Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.