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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 3  |  Page : 789-793

Is diabetic micro angiopathy a risk factor for variceal bleeding in diabetic cirrhotic patients?


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Internal Medicine, Ministry of Health, Tanta, Egypt

Date of Submission03-Feb-2019
Date of Decision28-Feb-2019
Date of Acceptance02-Mar-2019
Date of Web Publication30-Sep-2020

Correspondence Address:
Mohammed K Saad
Tanta, Gharbiya 31742
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_34_19

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  Abstract 


Objective
To study the impact of diabetic microangiopathy on the outcome of cirrhotic patients with variceal bleeding.
Background
There are various risk factors for variceal bleeding in cirrhotic patients such as diabetes mellitus, and so follow up of these patients to determine the effects of diabetic microangiopathy on presentation, course, and mortality is mandatory to improve the plane of care.
Patients and methods
This study is an observational–analytic case–control hospital-based study, which was conducted on 60 patients admitted with acute variceal bleeding. Based on the WHO criteria of diabetes mellitus, the patients were divided into three groups. Group I: 20 diabetic cirrhotic patients with microvascular complications, group II: 20 diabetic cirrhotic patients without microvascular complications, and group III: 20 cirrhotic patients only. All patients were subjected to: full history, clinical examination, complete blood count, liver functions, kidney functions, fasting and 2 h postprandial blood glucose, glycated hemoglobin, vascular endothelial growth factor assay, abdominal ultrasound, fundus examination, monofilament test, and upper gastrointestinal endoscopy.
Results
The results showed that the mean frequency of rebleeding attacks was significantly higher in group I than other groups and the mean length of hospital stay was significantly higher in group I than other groups. The mortality rate during the period of follow-up was higher in group I than other groups.
Conclusion
The study showed that cirrhotic patients with diabetic microangiopathy are associated with increased risk of rebleeding esophageal varices, multiple admissions to hospital, long hospital stay, and mortality rate higher than other patients.

Keywords: cirrhotic, diabetic microangiopathy, variceal bleeding


How to cite this article:
Dala AG, Badr MH, Abou Elnour ESS, Saad MK. Is diabetic micro angiopathy a risk factor for variceal bleeding in diabetic cirrhotic patients?. Menoufia Med J 2020;33:789-93

How to cite this URL:
Dala AG, Badr MH, Abou Elnour ESS, Saad MK. Is diabetic micro angiopathy a risk factor for variceal bleeding in diabetic cirrhotic patients?. Menoufia Med J [serial online] 2020 [cited 2020 Oct 28];33:789-93. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/789/296666




  Introduction Top


Acute variceal bleeding is the major cause of upper gastrointestinal (GI) bleeding in cirrhotic patients; it represents about 70% of cases [1]. At least two-thirds of patients with liver cirrhosis develop esophageal varices during the course of their disease, and severe upper GI bleeding is a common complication of portal hypertension, affecting 30–40% of patients with cirrhosis [2]. Its rupture is associated with a mortality of at least 20% at 6 weeks in spite of upgrades in treatment. However, it has diminished from 47 to 13% with utilization of pharmacological, radiological, and endoscopic intervention [3]. The major predictors for early mortality of acute variceal bleeding in liver cirrhosis include hepatic encephalopathy, Child–Pugh score or class, Model for End-Stage Liver Disease score, shock, renal failure, infection, hepatocellular carcinoma, active bleeding, portal vein thrombosis, and hepatic venous pressure gradient [4]. Diabetes mellitus (DM) is frequently seen in patients with cirrhosis, especially because of hepatitis C virus (HCV) infection. However, no studies have focused on the clinical significance of diabetic control in cirrhotic patients because of their short life expectancy and poor hepatic function [5]. Numerous researchers have investigated the impact of DM on the clinical results of patients with certain medical conditions or surgeries [6]. Most prognostic parameters used in clinical routine today are not reliable enough in predicting a patient's vital threat posed by an upper gastrointestinal tract (GIT) bleeding [7]. The correlation between the DM and the clinical outcomes of patients with variceal bleeding could contribute to future studies about bleeding esophageal varices and have significant implications for the quality of patient medical care [8].

The aim of this study is to study the effects of DM on presentation, course, and mortality of acute variceal bleeding in cirrhotic patients.


  Patients and Methods Top


This study is an observational–analytic case–control hospital-based study, which was conducted on 60 patients who were admitted with acute variceal bleeding to Menoufia University Hospitals and Almogama Elteby Hospital in Tanta for about 15 months from March 2017 to June 2018 with a follow-up period of an average 6 months. The study was approved by the Ethics Committee of Menoufia Faculty of Medicine. All patients gave a written informed consent before inclusion into the study. Based on WHO criteria for the diagnosis of DM. the patients were divided into three groups. Group I consisted of 20 patients, who were diabetic cirrhotic (DC) with microvascular complications, group II consisted of 20 patients, who were DC without microvascular complications, and group III consisted of 20 patients who were cirrhotic only. The patient was considered to have diabetic complications if he had at least one of the followings retinopathy, neuropathy, or nephropathy. There are exclusion criteria such as patients with upper GI bleeding from nonvariceal causes, patients with known advanced cardiac diseases and renal diseases, patients with hepatocellular carcinoma and other malignancies, patients with proven portal vein thrombosis, and patients with Budd–Chiari syndrome. The selected patients were subjected to the following measures: full history includes age, sex, medications intake, history suggestive of constant liver sickness, past attacks of hematemesis, and/or melena and history of hepatic encephalopathy. Also, history of chronic illnesses such as DM, hypertension, renal disease, and ischemic heart disease was taken. Clinical examinations include general, physical, and abdominal examination. Laboratory investigations include complete blood count, viral markers (HCV antibody, hepatitis B virus antigen), aspartate transaminase, alanine transaminase, serum albumin, total and direct bilirubin, alkaline phosphatase, international normalized ratio, serum creatinine, blood urea, fasting and 2 h postprandial blood glucose, glycated hemoglobin, and vascular endothelial growth factor (VEGF) assay. Radiological investigations include abdominal ultrasound, abdominal computed tomography to assess liver cirrhosis, portal hypertension, ascites, and exclusion of focal lesions. According to Child–Pugh scoring system for grading the severity of liver dysfunction, the patients were classified according to the Child–Pugh score into Child A, Child B, and Child C. Upper GI endoscopy was done to all patients to diagnose the cause of bleeding, control bleeding, assess and to classify the size and appearance of esophageal varices and to exclude other causes of bleeding such as ulcers and tumors. Other investigations such as albumin/creatinine ratio, fundus examination, and monofilament tests were performed to detect diabetic microvascular complications. The results were tabulated and were statically discussed.

Follow-up

Patients after admission to hospital with acute variceal bleeding and control of the bleeding were discharged and followed up for 6 months to assess rebleeding, mortality rates, number of hospital admissions, and length of hospital stay.

Statistical analysis

All data were collected, tabulated, and statistically analyzed. Analysis of data was performed with a personal computer using the Statistical Package for the Social Sciences program for Windows (version 20; IBM Company, Armonk, New York, USA). Statistical presentation and analysis of the present study was conducted using the mean, SD, χ2, and analysis of variance test.


  Results Top


Our results showed no significant difference between the studied groups with regard to their demographic data, including sex, age, and etiology of liver cirrhosis. Most of our patients were HCV-related cirrhosis (76.6%) due to the high prevalence in our region; hepatitis B virus were 6.7% of cases and other causes of cirrhosis were 16.7%. Among our selected diabetic patients about 15% were of type 1, 85% were of type 2, 52.5% on insulin therapy, and 47.5% on oral hypoglycemic drugs. Our results also showed no significant difference between the studied groups as regard to Child–Pugh score as P > 0.05. This may be explained by our equal randomization of our patients regarding Child–Pugh class between the studied groups [Table 1].
Table 1: Demographic characteristics and clinical data in the studied groups

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The laboratory data that included hematological parameters such as hemoglobin concentration, red blood cell counts, white blood cell, and platelet counts showed no significant difference between the studied groups (P > 0.05) and liver function tests such as aspartate transaminase, alanine transaminase, serum total and direct bilirubin, serum albumin, and alkaline phosphatase showed no significant difference between the studied groups (P > 0.05). The mean serum creatinine was significantly different in group I than other groups (1.42 ± 0.42, 1.07 ± 0.37, and 1.05 ± 0.34, respectively) with P value equal to 0.0041 and the mean serum urea was significantly different in group I than other groups (101.1 ± 31.6, 45 ± 6.98 and 33.68 ± 6.89, respectively) with P value less than 0.0001 and the mean albumin creatinine ratio also was significantly different in group I than other groups (172 ± 118.5, 30 ± 12.27, and 17.89 ± 6.77, respectively) with P value less than 0.0001. The blood glucose level in the studied groups, fasting, 2 h postprandial, and glycated hemoglobin showed a significant difference (P < 0.0001) between nondiabetic and diabetic groups [Table 2]. The mean VEGF showed a significance difference (P < 0.0001) between the three studied groups as it was higher in group I than other groups (155.2 ± 88.58, 44.36 ± 12.98, and 39.02 ± 10.14, respectively) [Table 3]. The mean frequency of rebleeding attacks among the studied groups was significantly different in group I than other groups (4.34 ± 1.84, 2.01 ± 1.01, and 1.41 ± 0.48, respectively) with P value less than 0.0001 and the mean length of hospital stay was significantly different in group I than other groups (4.32 ± 0.81, 3.24 ± 0.74, and 2.51 ± 0.52, respectively) with a P value less than 0.0001 [Table 4]. The mortality rate during the period of follow-up was higher among group I (35%), low in group II (10%), and lower in group III (5%) with significant difference (P = 0.024) [Table 5]. By studying the area under the receiver operating characteristic curve analysis for prediction of variceal bleeding in group I, the VEGF at a cutoff of 178 pg/ml showed a diagnostic sensitivity of 72.73%, specificity of 87.50%, positive predictive value of 88.9%, and negative predictive value of 70% [Figure 1].
Table 2: Laboratory data in the studied groups

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Table 3: Mean values of vascular endothelial growth factor in the studied groups

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Table 4: Comparison between the studied groups as regards frequency of rebleeding attacks and length of hospital stay

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Table 5: Outcome of rebleeders in the studied groups

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Figure 1: ROC curve of VEGF sensitivity and specificity in DC patients with microvascular complications. DC, diabetic cirrhotic; ROC, receiver operating characteristic; and VEGF, vascular endothelial growth factor.

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  Discussion Top


Our study has shown that the DC with microvascular complications patients significantly suffered from higher rebleeding rate than other patients, which agreed with the study done by Yang et al. [9] who found that the rate of variceal bleeding was higher in cirrhotic patients with DM than in cirrhotic patients without DM. After doing upper GIT endoscopy for our patients, we found that the DC with microvascular complication patients suffered from advanced grades of esophageal varices (III, IV) more than others as several studies have suggested that diabetic angiopathy impairs mucosal integrity and so increases the risk for acute GI injury and impairs mucosal healing leading to more severe bleeding [10]. Therefore, angiopathy due to DM could make the control of bleeding more difficult and may impact in-hospital mortality of patients with bleeding varices. This may be explained by the high rate of recurrent attacks of variceal bleeding. These results agreed with another study in Pakistan done by Majid et al. [11] who reported that DC patients with bleeding gastroesophageal varices have a worse outcome due to failure to control bleeding, rebleeding during hospital stay, multiple admissions with variceal bleeding, and the presence of anemia as compared with non-DC patients. Previous study done by Coskun et al. [12] concluded that upper GI bleeding is higher in diabetic patients than the nondiabetic patients with cirrhosis. Also, they reported that DM influenced rebleeding or death in patients admitted to the emergency room with upper GIT bleeding necessitating intensive care. In this study, we measured the levels of VEGF, which may reflect the severity of endothelial dysfunction in patients with DM, which leads to diabetic microvascular complications [13].

As regard the association between DM and prolonged hospitalization, our study demonstrated that cirrhotic patients with uncontrolled DM had longer in-hospital stay which agreed with a study done by Francesca et al. [14] who reported that patients with DM who are hospitalized for other health problems may have increased risk of in-hospital death and longer hospital stay. Another study also showed a strong association between uncontrolled DM and prolonged hospitalization [15].

In addition, the current study demonstrated that DM significantly increases in-hospital mortality in patients with bleeding esophageal varices after adjustment for other chronic comorbid conditions as the cases who died reported along the duration of follow-up were higher among DC with complications group which agreed with a study done by Qi et al. [16] who reported that diabetes is associated with an increased risk of in-hospital mortality in liver cirrhosis with acute upper GI bleeding.


  Conclusion Top


Our study demonstrated that diabetic microangiopathy is associated with increased risk of rebleeding and multiple admissions in cirrhotic patients with esophageal varices. Also it has been demonstrated that diabetic microangiopathy increased the length of hospital stay and in-hospital mortality in patients with bleeding esophageal varices after adjustment for other chronic, comorbid conditions and factors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Rudler M, Rousseau G, Benosman H, Massard J, Deforges L, Lebray P, et al. Peptic ulcer bleeding in patients with or without cirrhosis: different diseases, but the same prognosis. Aliment Pharmacol Ther 2012; 36:166–172.  Back to cited text no. 1
    
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Peter S, Frank D, Genevieve DA, Volkmar H, Klaus B, Christian H, Stefan R. The vital threat of an upper gastrointestinal bleeding: risk factor analysis of 121 consecutive patients World J Gastroenterol 2006; 12:3597–3601.  Back to cited text no. 7
    
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Ishihara M, Kagawa E, Inoue I, Kawagoe T, Shimatani Y, Kurisu S, et al. Impact of admission hyperglycemia and diabetes mellitus on short and long-term mortality after acute myocardial infarction in the coronary intervention. Am J Cardiol 2007; 99:1674–1679.  Back to cited text no. 8
    
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Yang CH, Chiu YC, Chen CH, Chen CH, Tsai MC, Chuah SK, et al. Diabetes mellitus is associated with gastroesophageal variceal bleeding in cirrhotic patients. Kaohsiung J Med Sci 2014; 30:515–520.  Back to cited text no. 9
    
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Konturek PC, Brzozowski T, Burnat G, Szlachcic A, Koziel J, Kwiecien S, et al. Gastric ulcer healing and stress-lesion preventive properties of pioglitazone are attenuated in diabetic rats. J Physiol Pharmacol 2010; 61:429–436.  Back to cited text no. 10
    
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Majid S, Azam Z, Shah HA, Salih M, Hamid S, Abid S, Jafri W. Factors determining the clinical outcome of acute variceal bleed in cirrhotic patients. Indian J Gastroenterol 2009; 28:93–95.  Back to cited text no. 11
    
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Coskun F, Topeli A, Siviri B. Patients admitted to the emergency room with upper gastrointestinal bleeding: factors influencing recurrence or death. Adv Therapy 2005; 22:453–461.  Back to cited text no. 12
    
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Qin Z, Wen F, Li M, Zhao DW, Yun MY, Yuan QL. VEGF levels in plasma in relation to metabolic control, inflammation, and microvascular complications in type-2 diabetes. Medicine (Baltimore) 2018; 97:e0415.  Back to cited text no. 13
    
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Francesca V, Laura T, Franco G. Does diabetes mellitus comorbidity affect in-hospital mortality and length of stay? Analysis of administrative data in an Italian Academic Hospital. Acta Diabetol 2017; 54:1081–1090.  Back to cited text no. 14
    
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Moghissi ES. Addressing hyperglycemia from hospital admission to discharge. Curr Med Res Opin 2010; 26:589–598.  Back to cited text no. 15
    
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Qi X, Peng Y, Li H, Dai J, Guo X. Diabetes is associated with an increased risk of in-hospital mortality in liver cirrhosis with acute upper gastrointestinal bleeding. Eur J Gastroenterol Hepatol 2015; 27:476–477.  Back to cited text no. 16
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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