Hepatitis C Virus (HCV) infection is a major public health problem, which currently affects over 200 million people, with an estimated prevalence of 2.2% globally [1] . Egypt has the highest prevalence rate of HCV in the world, making it the most challenging health problem facing the country. Studies show that 14.7% of the Egyptian population carry HCV antibodies [2] and 9.8% have an active infection [3] .

The wave of increased HCV-related morbidity and mortality is likely due to the widespread availability of injectable therapies and the illicit use of injectable drugs [4] . Currently the association between HCV infection and T2DM had been reported in a number of clinical studies though conflicting results were reported [5] [6] .

Both diabetes and HCV infection are severe health problems worldwide, especially in the developing countries [7] [8] . A range of extra-hepatic manifestations such as arthralgia, thyroiditis and diabetes are linked with HCV infections [9] . Studies have shown that patients infected with HCV have more glucose intolerance than the general population [10] [11] .

The mechanism of pathogenesis of diabetes in patients with HCV infection remains unclear though it has been implicated that insulin resistance plays an important role and is related to fibrosis score [12] .

T2DM is a major public health problem worldwide that is rapidly emerging due to increasing prevalence of obesity and sedentary lifestyle [8] . Aging, obesity, family history of diabetes, and Human Immunodeficiency Virus (HIV) co-infection are recognized influencing factors associated with diabetes development among HCV- infected patients [13] .

Several studies from different parts of the world have found that 13% to 33% of patients with chronic HCV have associated diabetes, mostly T2DM [14] [15] . In Egypt, some studies have reported that the prevalence of T2DM among HCV patients is 25.4% [16] and that chronic HCV patients are three times more likely to develop T2DM than HCV seronegative patients [17] . Therefore, it is important to identify the magnitude of the problem of DM in order to optimize the cost and reduce failure of treatment in HCV patients who are at risk to develop T2DM.

The aim of this study was to elucidate the presence of association between HCV and T2DM and explore the factors that might be predicting the occurrence of DM in patients with HCV considering other known possible DM risk factors. Furthermore, the study is invented to provide valuable insight regarding usefulness of focused screening program in HCV to improve patients’ outcome and quality of services.

Data analysis was carried out using SPSS software for Windows, version 21 Statistical Package of Social Sciences (SPSS Inc., Chicago, IL) [21] . Descriptive analysis was performed and the results were expressed as mean ± SD and percentages. Comparison between groups (cases and controls) was done using the Student’s t test for continuous variables and Pearson chi-square test for nominal categorical variables. Logistic regression analysis was used to evaluate the predictive variables that could be associated with the presence of diabetes. Odds ratio (OR) and their respective 95% confidence intervals (CI) were calculated. P value of ≤0.05 was considered statistically significant.

After explaining the purpose of the study, a written informed consent was taken from the participants before collecting data and taking samples. The current research was approved by the ethics committee of the KAH and was conducted in accordance with Helsinki declaration [22] .

In this study, a total of 778 participants (389 HCV cases and 389 non HCV controls) were included. Out of this total, DM was found in 364 patients; 219 (56.3%) HCV cases and 145 (37.3%) non HCV controls, 342 patients were aware of their problem, whereas 22 cases were newly diagnosed. There was a two fold increase in the percentage of diabetes among HCV cases as compared to non HCV controls [Figure 1], and the mean duration of diabetes among known diabetic patients was (7.41 ± 3.82) years.

There is a growing body of literature on the link between T2DM and HCV, however, studies are contradictory

^*Statistically significant value < 0.05; ^†Total cases = 36, controls = 16.

^*Statistically significant value < 0.05; ^†Total cases = 32, controls = 36.

R = 0.238; P < 0.001; ^*Statistically significant value < 0.05; OR: Odds ratio, CI: Confidence interval.

and the data is inconclusive [23] [24] . Recent data had suggested that the prevalence of T2DM in HCV seropositive patients is three times higher compared to non HCV controls [25] - [27] . The present study found a strong association between HCV and T2DM, however, 22 diabetic cases were unaware of their endocrinal problem before being screened. The later findings highlight the importance of periodical screening for HCV patients especially in advanced stages. In contrast, some studies provided evidence against a potential association between these two disorders [16] [28] [29] .

In Egypt the estimated prevalence of overt DM in adult ranges from 10% to 20% [30] , which is about 2 to 3 times less than what was found in this study (56.5%), indicating that patients with HCV are a high-risk population for DM. This is in agreement with a previous study done in India [31] but in contrast with others [10] [32] . This contradiction may be attributed to differences in environmental factors, genetic susceptibility and diet.

Consistent with other previous studies [16] [27] , HCV cirrhotic patients had a significantly higher prevalence of DM than non-cirrhotic patients. In contrast, Giordanino et al. 2008 [33] reported different findings. The discrepancies among studies may be explained by the degree of severity of liver disease. Expectedly, the current study revealed an independent association between cirrhosis and DM rate (OR = 1.7). Similarly, studies from different areas [34] [35] proves that advancing liver disease increased susceptibility of HCV seropositive patients to develop T2DM.

Age is another definite risk factor for T2DM in the normal population [20] . In this study HCV diabetic cases were older than non HCV diabetic subjects, which is interestingly similar to the findings of other studies [36] [37] by supporting the idea that the occurrence of diabetes in HCV patients is progressive rather than abrupt [15] . Other studies suggest that HCV interferes with glucose metabolism independently of age. [21] [24] Therefore, screening for and prevention of diabetes in persons with HCV infection should be started earlier than the suggested age of ≥45 years for the general population [28] .

Diabetes as a disease affects both the male and female gender [38] . In this study, there were more female diabetic patients positive for anti-HCV antibodies than their male counter parts, which corroborates an earlier report by Huang et al. 2007 [39] .

HCV patients with T2DM tended to have lower educational attainment in comparison to non diabetics [24] . The present study showed a significant association between educational level and HCV Ab seroprevalence (P < 0.001) and this agrees with the work done by Rajesh et al. 2012 [40] . High prevalence of HCV in illiterate people may be attributed to many factors such as paucity of health education programs about chronic viral hepatitis in educational systems and inaccurate estimates of the burden of disease.

In the present study, both bivariate and regression analysis showed that the occurrence of diabetes among HCV cases was independently related to occupation and residence, where most of the HCV cases were skilled workers and from urban localities in comparison to non HCV diabetic controls. This agrees with the work of Elhawary et al. 2011 [16] who observed the same findings.

Habitual smoking is a well-documented risk factor for exacerbation of liver conditions [41] . There was a history of cigarette smoking among 62.7% of HCV diabetic subjects in comparison to 37.3% of non HCV diabetic subjects. This finding is similar to that reported by Eissa et al. [42] but in contradiction with Alavian et al. [43] who noted lower figures.

Although DM was associated with hypertension in bivariate analysis, it lost its significance as a predictor of DM in the logistic regression model after adjustment for other related variables. It is currently believed that the presence of cardiovascular disease is rare in cirrhosis and that cirrhotic patients have a low prevalence of vascular disease including hypertension even in the presence of overt DM [44] . The current study supported this hypothesis showing no difference in the rate of hypertension between diabetic HCV cases and controls.

Family history of DM is a well-known risk factor for DM. The correlation between DM and HCV in this study remained significant even when family history of DM was entered through logistic regression model. When diabetes groups were analyzed separately among studied HCV patients, it was observed that patients with a positive family history of DM did not show an increased frequency of DM. Interestingly, this coincides with the work of Nadok et al. 2009 [45] who indicated that liver injury per se was associated with DM and that a family history of DM was only an adjunctive factor.

Overweight and obesity are major causes of fatty liver disease, insulin resistance, and T2DM [46] . Coexistence of HCV infection and overweight increases the risk of developing diabetes. In the current study, high BMI was one of the factors associated with the occurrence of diabetes among HCV cases, but it lost its significance in the logistic regression model. This finding shows that the diabetogenic effect of HCV infection is nearly similar to the effect of overweight and obesity [47] . This finding is important for public health and clinical practice because the prevalence of HCV infections endemic in some developing countries and high-risk groups in developed countries because of unsafe injections and intravenous drug use [41] . Therefore, it is particularly important for HCV-infected persons to change their lifestyle to control their body weight to prevent the development of diabetes.

In a study conducted by Harris (2005), individuals with T2DM had a higher incidence of liver function test (LFT) abnormalities than non diabetics [48] , which is similar to the findings of this study. However, Chehadeh et al. [15] found no difference in this aspect. In present study, levels of liver enzymes and cholesterol in diabetics were higher in HCV cases compared with non-HCV controls, which may have therapeutic implications in the management of patients with HCV. It is necessary to emphasize weight control in overweight patients in order to decrease both the risk of DM and to prevent liver damage. Since the co-infection ofT2DM and HCV has been established to worsen each other, it is crucial to perform screening tests to determine the prevalence of T2DM among HCV patients.

In relation to glycemic control, it was noted that patients with bad glycemic control were at more at risk of having HCV infection as compared to those with good glycemic control, which goes in accordance with Jadoon et al. 2010 [49] who reported the same finding. This may be because of various confounding factors, which warrants further investigation. In this regard, screening for diabetes should be indicated in these patients.

The most important limitations in this study were: small sample size, hospital-based study and the difficulty of testing for HCV RNA in a teaching hospital like Cairo University due to the very high cost and limited facilities.

There is a significant association between HCV infection and T2DM. However, it remains unclear whether HCV infection is a risk factor for diabetes or vice versa. Development of T2DM increases by nearly two folds if an HCV patient has cirrhosis. Residence, occupation and smoking were the predictive factors for the association of T2DM in HCV patients, whereas hypertension and BMI were only adjunctive factors. Further studies regarding the association of the two conditions are needed to illustrate the relationship and improve management strategies. Limited resources for HCV prevention in Egypt necessitate that healthcare policy-makers should implement prevention strategies and infection control programs in healthcare settings to avoid the double burden of HCV and DM and to improve the overall quality of care.

We acknowledge the Internal Medicine and Clinical Pathology Departments, Faculty of Medicine, Cairo University. The authors would like also to thank all nurses who helped in collecting the samples. The research team thanks all patients for their co-operation.

Shaimaa B.Abdelaziz,Yasmine S.Galal,Amal S.Sedrak,Dina S.Shaheen, (2016) Association of Hepatitis C Virus Infection and Type 2 Diabetes in Egypt: A Hospital-Based Study. Journal of Diabetes Mellitus,06,77-89. doi: 10.4236/jdm.2016.61009