Hepatitis C Virus Infection: A Risk Factor for Type 2 Diabetes?

Hepatitis C virus (HCV) infection is a widespread condition that affects up to 170 million people worldwide, or 3% of the global population. Liver cirrhosis and hepatocellular carcinoma are well-known complications of HCV infection, but extrahepatic manifestations develop in up to two-thirds of patients with HCV.¹ Extrahepatic manifestations account for the increasing disease burden of HCV in spite of declining rates of HCV infection in the United States.²

HCV-related disorders include lymphomas and renal, metabolic, and cardiovascular diseases.¹ The risk of type 2 diabetes (T2D) and insulin resistance appears to be increased in patients with HCV as well. The elevated risk for T2D is present both in patients without liver dysfunction and in patients with chronic HCV-related liver disease.²

The Link Between HCV and T2D

Up to 30% of patients with HCV have insulin resistance or T2D, and patients with HCV are 1.5 to 3.8 times as likely to have T2D than the general population. Patients with HCV who are at high risk for T2D due to non-HCV-related risk factors have an 11-fold greater risk of developing T2D than individuals without HCV.³

While epidemiological data largely support the association between HCV infection and T2D, not all studies are in agreement.³ One prospective study from 1998 compared the risk of T2D in 247 patients with liver cirrhosis, 138 patients with chronic hepatitis, and 494 patients with acute orthopedic trauma. HCV infection was present in 64% in the cirrhosis group and 74% of patients in the chronic hepatitis group. Age and cirrhosis were independent predictors of T2D, but HCV infection was not. However, a major limitation of this study was that T2D was diagnosed using fasting plasma glucose alone.⁴

A recent study from 2014 also did not find a link between HCV infection and T2D. This population-based study analyzed cross-sectional data from 15,128 adults from the US National Health and Nutrition Examination Survey (NHANES). A total of 1.7% of participants were positive for HCV antibodies, 1.1% were positive for HCV RNA, and 10.5% had T2D. Insulin resistance was measured using homeostatic model assessment-estimated insulin resistance (HOMA-IR), and T2D was diagnosed using hemoglobin A1C and fasting plasma glucose. Increased alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) levels were identified as risk factors for T2D. No association between HCV and T2D was found.⁵

Although the NHANES study appeared to refute the relationship between HCV infection and T2D, Yaron Tomer, MD, an endocrinologist from the Albert Einstein College of Medicine in New York, does not believe that these results necessarily disprove the connection. “In the NHANES study, while not statistically significant, there was a trend for higher HOMA-IR, which is a measure of insulin resistance, in patients with HCV,” he said.

“Also, the evidence supporting the association between HCV and T2D goes back almost 20 years and comes from all over the world. I think that there is an association after reviewing the bulk of the data,” he added.