Hepatitis C May Be a Cause of Diabetes

October 25, 1996

Disease Associations (HCV)

Hepatitis Weekly via Individual Inc. :
Hepatitis C virus may have a direct role in the development of diabetes, according to a report from Spain. Researcher Rafael Simo and colleagues found a high prevalence of hepatitis C virus (HCV) infection in patients with diabetes, and found that most HCV patients presented with abnormal liver function tests. "Testing for HCV infection of diabetic patients with an abnormal liver function test is mandatory," Simo et al. wrote ("High Prevalence of HCV Infection in Diabetic Patients," Diabetes Care, September 1996;19(9):998- 1001). "The lack of any particular epidemiological factor for HCV infection in our diabetic population suggests that HCV may have a direct role in the development of diabetes." Mild asymptomatic elevations of serum aminotransferases in a diabetic patient do not receive much attention because they are often attributed to fatty infiltration. It has been hypothesized that, during the course of the disease, diabetic patients are more prone to acquire an HCV infection because they are subjected to more frequent medical interventions. While a link between diabetes and HCV has recently been suggested, a controlled study of prevalence and risk factors for HCV infection has not yet been performed. "The aim of this study was to evaluate the prevalence of HCV infection in diabetic patients attending our outpatient clinic in comparison with blood donors who were matched for the main risk factors associated with anti-HCV seropositivity," Simo et al. wrote. "Furthermore, we investigated the influence of several epidemiological and clinical factors on HCV infection in diabetic patients, including type of diabetes, duration of the disease, mode of therapy, and presence of late complications." A total of 176 consecutive diabetic patients were compared with 6172 blood donors, matched by recognized risk factors to acquire HCV infection. Serologic testing for anti-HCV was done using a second-generation commercial enzyme-linked immunosorbent assay (ELISA), and an immunoblot assay was performed in anti-HCV positive samples to confirm HCV specificity. Diabetic patients were divided into two groups according to their HCV antibody status and analyzed for age, sex, type of diabetes, duration of disease, mode of therapy, late diabetic complications, previous blood transfusion, intravenous drug addiction, hospital admissions, major surgical procedures, and liver function tests. Anti-HCV was detected in 18 diabetic patients and 156 blood donors (11.5 versus 2.5 percent; P < 0.001). The estimated risk for HCV infection in diabetic patients was 4.39 times higher (95 percent CI 2.61-7.24) than in the control group. In addition, Simo et al. did not observe a significant difference for previous blood transfusion (21.8 versus 16.7 percent) and intravenous drug addiction (10.2 versus 5.5 percent) between blood donors and diabetic patients with HCV infection, respectively. Only age (63.8 +/- 10.2 versus 49.4 +/- 17.8 years) and previous blood transfusion (16.7 versus 1.2 percent; P < 0.05) were statistically related to HCV infection. After excluding the three anti-HCV positive diabetic patients with previous blood transfusion, the global prevalence of anti-HCV seropositivity in the diabetic population (15 of 175, or 8 percent) remained significant in comparison with the control group (P < 0.001; odds ratio 3.59; 95 percent CI 2.04-6.23). Furthermore, the three anti-HCV positive diabetic patients with previous blood transfusion were transfused for unrelated diseases seven, 15, and 23 years before diagnosis of diabetes. In anti-HCV positive diabetic patients, abnormal liver function tests were seen in 72.3 percent, compared with only 24.7 percent of anti-HCV negative diabetic patients (P < 0.001). "Diabetic patients have a high prevalence of abnormal liver function tests that are often attributed to fatty infiltration without further investigation," Simo et al. wrote. "In this study, we have demonstrated for the first time that diabetic patients present a higher prevalence of HCV infection than control subjects who are matched for the main risk factors, such as age, previous blood transfusion, and intravenous drug addition. In addition, most of anti-HCV positive patients presented with an abnormal liver function test, being a combination pattern of cytolysis and cholestasis as the predominant biochemical alteration. We feel that this is an important point, since none of these patients had been previously diagnosed with liver disease, and diabetes was the only reason for referral to our unit. In consequence, based on our results, testing for HCV infection in diabetic patients with an abnormal liver function test is mandatory." The authors suggest their results could be interpreted to mean either that diabetic patients have some undiscovered epidemiological factor that increases the risk of acquiring HCV infection or that HCV infection may have some etiopathogenic role in the development of diabetes. In recent studies Allison et al. reported a significantly increased rate of diabetes in patients with HCV related cirrhosis, compared with other causes, and suggested that HCV infection has some etiopathogenic role in the development of diabetes (J Hepatol 1994;21:1135-1139). "Several possible mechanisms can be postulated to link HCV to diabetes," Simo et al. wrote. "It may be possible that HCV, similar to the hepatitis B virus, could infect pancreatic islet cells and thereby induce damage to (alpha)-cells. On the other hand, HCV has been related to diseases in which the autoimmune phenomena play an important role, such as cyroglobulinemia, glomerulonephritis, thyroiditis, and Sjogren disease. Therefore, an autoimmune destruction of endocrine pancreatic tissue related to HCV antigens or immunocomplexes cannot be excluded."

The corresponding author for this study is Rafael Simo, Department of Endocrinology, Hospital General Universitari Vall d'Hebron, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.

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