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ORIGINAL ARTICLE
Year : 2016  |  Volume : 29  |  Issue : 2  |  Page : 209-214

Retinopathy in type 2 diabetes mellitus patients with and without chronic hepatitis C virus infection


1 Department of Internal Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Menoufia University, Menoufia, Egypt
3 Department of Ophthalmology, Menoufia University, Menoufia, Egypt

Date of Submission02-Jul-2014
Date of Acceptance04-Jul-2014
Date of Web Publication18-Oct-2016

Correspondence Address:
Walaa Abd El-Elah Darwish
MBBCh, Internal Medicine Department, Faculty of Medicine, Menoufia University, Shebin Al-Kom, Menoufia, 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.192482

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  Abstract 

Objective
The aim of the study was to evaluate the effect of chronic hepatitis C virus (HCV) infection in the prevalence of diabetic retinopathy.
Background
Diabetes mellitus (DM) is associated with significant morbidity and mortality as a result of both microvascular and macrovascular complications. Type 2 diabetes mellitus (T2DM) and HCV infection are two major public health problems worldwide.
Patients and methods
In this study, we examined 70 patients with T2DM who were selected for this prospective study from the outpatient clinics of Internal Medicine and Ophthalmology Departments. Patients were classified into two groups: group I and group II: group I comprised 38 patients with T2DM without HCV infection. Group II comprised 32 patients with T2DM with positive HCV infection. All patients were subjected to detailed history taking, clinical examination, and laboratory investigations including complete blood picture, glycosylated hemoglobin (HbA1C) level, PCR test to prove the presence of HCV infection, prothrombin time, international normalized ratio, fibrinogen, platelet count and mean platelet volume, liver function tests including aspartate aminotransferase, alanine aminotransferase, serum albumin, and total serum bilirubin, and ophthalmoscopic examinations for diagnosis of diabetic retinopathy.
Results
Retinopathy was higher in T2DM patients: 27 (71.1%) patients were positive for retinopathy and 11 (28.9%) patients were negative, compared with chronic HCV-DM patients, among whom 13 (40.6%) were positive for retinopathy and 19 (59.4%) were negative. This difference is high enough to produce significant statistical difference (P = 0.014). Platelet count, fibrinogen concentration, and mean platelet volume were increased in diabetic retinopathy patients. International normalized ratio and prothrombin time levels were significantly higher in diabetic patients with chronic HCV infection than in diabetic patients without HCV infection.
Conclusion
Diabetic retinopathy was significantly higher in diabetic patients without chronic HCV infection than in diabetic patients with chronic HCV infection.

Keywords: Chronic hepatitis C virus infection, diabetes mellitus, retinopath


How to cite this article:
El-Kafrawy N, Dawood A, Khodeer S, Khairy H, Darwish WA. Retinopathy in type 2 diabetes mellitus patients with and without chronic hepatitis C virus infection. Menoufia Med J 2016;29:209-14

How to cite this URL:
El-Kafrawy N, Dawood A, Khodeer S, Khairy H, Darwish WA. Retinopathy in type 2 diabetes mellitus patients with and without chronic hepatitis C virus infection. Menoufia Med J [serial online] 2016 [cited 2020 Feb 24];29:209-14. Available from: http://www.mmj.eg.net/text.asp?2016/29/2/209/192482


  Introduction Top


Diabetes mellitus (DM) is a chronic disorder characterized by hyperglycemia and the late development of vascular and neuropathic complications. Regardless of its cause, the disease is associated with a common hormonal defect — namely, insulin deficiency that may be absolute or relative in the context of coexisting insulin resistance. The effect of insufficient insulin plays a primary role in the metabolic derangements linked to DM; hyperglycemia, in turn, plays an important role in disease-related complications [1].

Type 2 diabetes mellitus (T2DM) is frequently complicated by microangiopathy, such as diabetic retinopathy and nephropathy, and by macroangiopathy, such as ischemic heart disease and cerebrovascular disease [2]. Duration of DM and severity of hyperglycemia are the two major risk factors for diabetic retinopathy. After 5 years, ∼25% of patients with type 1 DM develop diabetic retinopathy; this increases to 80% after 15 years. Among patients with T2DM with a known duration of disease shorter than 5 years, 24–40% develop diabetic retinopathy. The prevalence increases to 53–84% after 19 years of DM [3].

Some evidence has suggested a decline during the past few decades in the prevalence and incidence of diabetic retinopathy, especially sight-threatening retinopathy. This reduction is attributed not only to improved care but also to the earlier detection of both DM and diabetic retinopathy [4].

Although the precise cause of these vascular complications remains uncertain, evidence is accumulating that an imbalance of hemostatic mechanisms may be involved in their initiation or progress [5].

Several studies have demonstrated the link between hepatitis C virus (HCV) infection and microvascular complications of DM (diabetic retinopathy, nephropathy, and neuropathy) as regards progression and development while other studies have failed to demonstrate such a link [6],[7].

HCV is the single most important cause of liver disease in Egypt. The highest HCV prevalence in the world occurs in Egypt at an estimated 22% in the general population [8].

The liver plays a central role in the maintenance of normal hemostatic function. Many of the proteins required for proper coagulation are synthesized in the liver, including prothrombin (factor II), fibrinogen, factors V, VII, VIII, X, XI, XII, and XIII, antithrombin III, and plasminogen. There is evidence that cirrhotic patients may have enhanced consumption of coagulation factors [9].

Among patients with liver cirrhosis, 20–30% have been reported to have DM, and if borderline cases are included over 80% have abnormal glucose metabolism of hepatic etiology. In these patients, the incidence of microangiopathy and macroangiopathy is thought to be low [2].

The low prevalence of diabetic retinopathy in diabetic patients with hepatitis C chronic liver diseases may be related to liver disease-induced abnormalities protecting the cardiovascular system from atherosclerosis (hypotension, coagulation defect, and decreased platelet count) [6].


  Patients and Methods Top


Data collection and patients

The study was carried out in Menoufia University Hospital during July 2012 to May 2013. Seventy patients with T2DM were selected for this prospective study from the outpatient clinics of Internal Medicine and Ophthalmology Departments. The patients were classified into two groups: group I comprised 38 patients with T2DM but without HCV infection and group II comprised 32 patients with T2DM and proved to have positive HCV infection.

Exclusion criteria

Patients with type 1 DM, pregnant women with T2DM, those with other causes of retinopathy, patients with advanced liver disease, and patients with renal failure were excluded from the study.

All patients were subjected to the following: full history taking including demographic data (age, sex, duration of DM, and family history of DM); clinical examination (general examination and abdominal examination); laboratory investigations [complete blood picture, glycosylated hemoglobin (HbA1C) level, PCR test to prove the presence of HCV infection, prothrombin time (PT), international normalized ratio (INR), fibrinogen, platelet count, mean platelet volume (MPV), and liver function tests including aspartate aminotransferase, alanine aminotransferase, serum albumin and serum bilirubin (total)]; and instrumental investigations such as ophthalmoscopic examination and stereoscopic dilated fundus examination using a slit lamp with +90.0 D lens.

Statistical analysis

Data were collected and entered into a computer the statistically analyzed using statistical package for social science (SPSS version 20 SPSS; SPSS Inc., Chicago, Illinois, USA). Data were entered as numerical or categorical, as appropriate. Two types of statistics were ascertained:

Descriptive statistics:

  1. Quantitative data were shown as mean, SD, and range.
  2. Qualitative data were expressed as frequency and percentage at 95% confidence interval.


Analytical statistics:

  1. The χ2-test was used to measure the association between qualitative variables.
  2. The t-test (Student's test) was used for comparison of quantitative variables between two independent groups.
  3. Multivariate analysis was used to investigate relationships among variables without designating some as independent and others as dependent.
  4. Significance was determined at the following P values:


  1. P-value more than 0.05 was considered insignificant (NS).
  2. P-value 0.05 or less was considered significant (S).



  Results Top


The comparison between HCV-positive patients and HCV-negative patients with regard to the results of the fundus examination ([Table 1]) revealed the following: diabetic retinopathy was present in 27 (71.1%) HCV-negative diabetic patients and 13 (40.6%) HCV-positive diabetic patients. The percentage of patients with diabetic retinopathy was significantly higher among HCV-negative diabetic patients compared with HCV-positive diabetic patients with significant difference between them (P = 0.014). Normal fundus examination was seen in 19 (59.4%) patients in the HCV-positive diabetic group and in 11 (28.9%) patients in the HCV-negative diabetic group; nonproliferative diabetic retinopathy was present in 11 (34.4%) patients of the HCV-positive diabetic group and in 16 (42.1%) patients of the HCV-negative diabetic group; and proliferative diabetic retinopathy was present in two (6.3%) patients of the HCV-positive diabetic group and in 11 (28.9%) patients of the HCV-negative diabetic group, with significant difference between them (P = 0.012). Macular edema was present in six (15.8%) patients of the HCV-negative diabetic group and in none (0%) of the patients in the HCV-positive diabetic group. The percentage of patients with macular edema was significantly higher among HCV-negative patients compared with HCV-positive patients, with significant difference (P = 0.019).
Table 1: Comparison of fundus examination results between hepatitis C virus-positive and hepatitis C virus-negative patients

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When HCV-positive diabetic patients with retinopathy were compared with those without retinopathy in terms of demographic data ([Table 2]) we found that the mean age was significantly higher in retinopathy-positive patients (65.8 ± 8.0 years) compared with retinopathy-negative patients (52.5 ± 5.0 years) (P ≤ 0.0001). The mean duration of DM was significantly higher in retinopathy-positive patients (14.76 ± 8.0 years) compared with retinopathy-negative patients (3.47 ± 2.38 years) (P ≤ 0.0001).
Table 2: Comparison of demographic data between patients with and those without retinopathy among hepatitis C virus-positive diabetic patients

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When HCV-negative diabetic patients with retinopathy were compared with those without retinopathy in terms of demographic data ([Table 3]) we found that the mean age was significantly higher in retinopathy-positive patients (63.6 ± 9.7 years) compared with retinopathy-negative patients (57.6 ± 5.7 years), with significant statistical difference (P = 0.018). The mean duration of DM was higher in retinopathy-positive patients (12.8 ± 1.0 years) compared with retinopathy-negative patients (3.0 ± 0.6 years), with significant statistical difference (P<0.01).
Table 3: Comparison of demographic data between patients with and those without retinopathy among hepatitis C virus-negative diabetic patients

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When HCV-positive diabetic patients with retinopathy were compared with those without in terms of PT, INR, fibrinogen, platelet count, and MPV ([Table 4]), we found that the mean PT level was significantly higher in retinopathy-negative patients (14.83 ± 0.74 s compared with retinopathy-positive patients (14.21 ± 0.61 s, with significant difference between them (P = 0.0238). The mean INR level was significantly higher in retinopathy-negative patients (1.24 ± 0.07) compared with retinopathy-positive patients (1.18 ± 0.05), with significant difference (P = 0.0180). The mean fibrinogen level was significantly higher in retinopathy-positive patients (312.38 ± 65.71 mg/dl) compared with retinopathy-negative patients (181.37 ± 37.10 mg/dl), with significant difference (P ≤ 0.0001). The mean platelet count was significantly higher in retinopathy-positive patients (291.0 ± 22.8 × 103/ml) compared with retinopathy-negative patients (203.7 ± 13.33 × 103/ml), with significant difference (P = 0.0014). The MPV was significantly higher in retinopathy-positive patients (9.754 ± 0.11 fl compared with retinopathy-negative patients (8.632 ± 0.16 fl), with significant difference (P ≤ 0.0001).
Table 4: Comparison of laboratory data between patients with and those without retinopathy among hepatitis C virus-positive diabetic patients

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When HCV-negative diabetic patients with retinopathy were compared with those without in terms of fibrinogen, platelet count, and MPV ([Table 5]), we found that the mean fibrinogen level was significantly higher in retinopathy-positive patients (363.0 ± 55.05 mg/dl) compared with retinopathy-negative patients (214.18 ± 40.52 mg/dl) with significant difference (P ≤ 0.0001). The mean platelet count was significantly higher in retinopathy-positive patients (315.0 ± 11.29 × 103/ml) compared with retinopathy-negative patients (244.09 ± 11.16 × 103/ml), with significant difference (P ≤ 0.0007). The MPV was significantly higher in retinopathy-positive patients (9.49 ± 0.109 fl) compared with retinopathy-negative patients (8.42 ± 0.107 fl), with significant difference (P ≤ 0.0001).
Table 5: Comparison of laboratory data between patients with and those without retinopathy among hepatitis C virus-negative diabetic patients

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Logistic regression analysis ([Table 6]) indicated that fibrinogen, INR, PT, duration of DM, and platelet count were significant independent factors for diabetic retinopathy among HCV-positive diabetic patients.
Table 6: Multivariate analysis of risk factors for diabetic retinopathy among hepatitis C virus-positive diabetic patients

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Logistic regression analysis ([Table 7]) indicated that the duration of DM, fibrinogen, platelet count, and MPV were significant independent factors for diabetic retinopathy among HCV-negative diabetic patients [Figure 1].
Table 7: Multivariate analysis of risk factors for diabetic retinopathy among hepatitis C virus-negative diabetic patients

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Figure 1: (a) Comparison of prothrombin time (PT) time between patients with and without retinopathy among hepatitis C virus (HCV)-positive diabetic patients. (b) Comparison of international normalized ratio (INR) between patients with and without retinopathy among HCV-positive diabetic patients. (c) Comparison of fibrinogen concentration between patients with and without retinopathy among HCV-negative diabetic patients.

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  Discussion Top


In the current study it was found that retinopathy was higher in patients with T2DM: 27 (71.1%) patients were retinopathy positive and 11 (28.9%) were retinopathy negative, compared with chronic HCV-DM patients, among whom 13 (40.6%) patients were retinopathy positive and 19 (59.4%) were retinopathy negative. This difference was high enough to produce a significant statistical difference (P = 0.014). This is in agreement with the results of studies carried out by El-Kafrawy et al. [6], Hemida et al. [8], El-Akkad et al. [0], Kuriyama et al. [1], Fujiwara et al. [2], and Sahar et al. [2], who reported that retinopathy was higher in chronic HCV diabetic patients compared with T2DM patients without HCV infection.

In contrast, Soma et al. [3] found that retinopathy was comparable in the two groups (47%) of chronic HCV-DM and (44.55) T2DM.

In our study we found that plasma fibrinogen level was slightly increased in HCV-negative diabetic patients compared with HCV-positive diabetic patients (P ≤ 0.0001). This finding was similar to that reported by Tamura et al. [4], who found that fibrinogen level was significantly lower in the DM with liver cirrhosis group than in the DM group.

Also we found that plasma fibrinogen level was increased in patients with diabetic retinopathy than in patients without retinopathy and the difference was statistically significant (P ≤ 0.0001). This is in agreement with the results of Kuzhuppilly et al. [5], in whose study fibrinogen values were significantly higher in the retinopathy group. On further comparison within the retinopathy group, no significant difference was seen between the nonproliferative diabetic retinopathy and proliferative diabetic retinopathy groups, suggesting that plasma fibrinogen may not contribute to the severity of retinopathy.

Also Vijaya et al., Son et al. [6], Asakawa et al. [7], Fujisawa et al. [2], and Borsey et al. [5] found that the higher serum fibrinogen level in the diabetic retinopathy group was an important risk factor for the development of retinopathy.

In the current study we found that the platelet count was higher in HCV-negative diabetic patients than in HCV-positive diabetic patients, which was statically significant (P = 0.013). This is in agreement with the results of El-Kafrawy et al. [6].

Also, studies carried out by El-Akkad et al. [0], Kuriyama et al. [1], and Fujiwara et al. [2] found higher platelet counts in diabetic noncirrhotic patients than in diabetic cirrhotic patients.

In the current study we found that the MPV was higher in retinopathy-positive patients with T2DM only compared with retinopathy-negative patients with T2DM only, and the difference was statistically significant (P ≤ 0.0001).

This is in agreement with the results of a study carried out by Tuzcu et al. [8], who found that MPV was significantly higher in patients with diabetic retinopathy compared with those without diabetic retinopathy.

Also Orhan et al. [9] and Zhong et al. [0] reported a significant correlation between MPV values and the degree of diabetic retinopathy.

In the current study we found a significant increase in PT in HCV-positive diabetic patients as compared with HCV-negative diabetic patients (P = 0.0008).

This is in agreement with the results of Kuriyama et al. [1], who found significant decreases in PT in patients with chronic liver disease with DM compared with diabetic patients.

In the current study we found that PT level was significantly higher in HCV-positive diabetic patients without retinopathy compared with those with retinopathy (P = 0.0238).

In conclusion, Colakoglu et al. [1] failed to find any statistically significant difference in PT among diabetic liver cirrhotic patients with any degree of retinopathy.


  Conclusion Top


Results of this study show that diabetic patients with chronic HCV infection had lower incidence of diabetic retinopathy compared with diabetic patients without chronic HCV infection. Platelet count and fibrinogen concentration increase in diabetic retinopathy and it seems to be more important in the pathogenesis of retinopathy (microvascular occlusion, neovascularization, and progression of retinopathy). INR and PT levels were significantly higher in diabetic patients with chronic HCV infection than in diabetic patients without HCV infection. This may allow the protective effects of CLD (through chronic HCV-induced thrombocytopenia, low coagulation functions, and low fibrinogen) to lower retinopathy in diabetic patients with chronic HCV infection compared with diabetic patients without chronic HCV infection.

Conflicts of interest

There are no conflicts of interest.[21]

 
  References Top

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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