Association of Hepatitis C With Insulin Resistance and Type 2 Diabetes in US General Population

The Impact of the Epidemic of Obesity

M. Stepanova; B. Lam; Y. Younossi; M. K Srishord; Z. M. Younossi


J Viral Hepat. 2012;19(5):341-345. 

In This Article

Abstract and Introduction


Studies from tertiary care medical centres have linked hepatitis C virus (HCV) to the development of insulin resistance (IR) and type 2 diabetes. The aim of the study is to assess the relationship between HCV positivity and insulin resistance/diabetes in the US population. Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 1988 and 2008 were used. HCV infection was diagnosed using a positive serologic anti-HCV test. Additionally, diabetes was diagnosed as fasting blood glucose ≥126 mg/dL and/or the use of hypoglycaemic medications. Insulin resistance was defined as a homeostasis of model assessment (HOMA) score of >3.0. Logistic regression was used to estimate the odds ratios (ORs) of each of the potential risk factors for diabetes mellitus (DM). The SUDAAN 10.0 was used to run descriptive and regression analyses. A total of 39 506 individuals from three NHANES cycles (1988–1994, 1999–2004 and 2005–2008) with complete demographic and relevant clinical data were included. Over these three NHANES cycles, prevalence of hepatitis C did not significantly change. During the first NHANES cycle (1988–1994), insulin and diabetes were independently associated with hepatitis C. However, during the later study cycles (1998–2008), these associations were no longer significant. In contrast, other important known risk factors for diabetes and IR (male gender, non-Caucasian race, age and obesity) remained significant over all three NHANES cycles. Although HCV infection was independently associated with an increased risk of diabetes and IR in the US population over a decade ago, assessment of the later NHANES cycles shows that this relationship may have become diluted by the rapid rise of other risks for diabetes, specifically, the prevalence of obesity.


Hepatitis C viral (HCV) infection has been suspected to affect glucose metabolism and predispose HCV-infected individuals to insulin resistance (IR) and type 2 diabetes diabetes mellitus (DM).[1,2] Although not entirely clear, the proposed mechanisms for HCV-related IR/DM may include direct pancreatic β-cell destruction, autoimmune β-cell injury and other mechanisms.[3–6] To support these hypotheses, one study has linked HCV core protein levels with IR as measured by increasing HOMA score values and decreasing the expression of insulin receptor substrate (IRS)-1 and IRS-2.[7] Findings of this study suggest that HCV can upregulate proteosomal degradation of IRS-1 and IRS-2, directly contributing to the development of insulin resistance.

In addition to the molecular mechanism for the interaction between HCV and IR/DM, there are clinical and epidemiological studies providing support for this association. Nevertheless, the clinical and the epidemiological data linking HCV with IR and DM come from both tertiary care medical centres and from population-based studies. In one such study, the prevalence of anti-HCV positivity in DM was 4.39-fold higher than in the matched blood donor controls.[8] In another study involving 1117 HCV and HBV patients, the prevalence of DM was 21% in HCV and 12% in HBV patients.[3] These results were subsequently supported by the Atherosclerosis Risk in Communities (ARIC) study reporting that HCV-infected individuals who were at risk for DM were 11 times more likely than those without HCV to develop overt DM.[9] Finally, a decade ago, a study analysing the data from the Third National Health and Nutrition Examination Survey (NHANES) (1988–1994) suggested that HCV infection in those aged ≥40 years was associated with 3.77-fold increased risk for DM.[10]

It is important to note that the findings from population-based studies reporting association between DM and HCV infection were based on the data collected in the 1980s and 1990s.[10,11] Given the rapid increase in the rate of obesity and DM in the US population in the recent decades, our understanding of the interaction between DM and HCV may benefit from re-examination of this population-based data. In this study, we use the recent NHANES data collections to assess association of HCV infection with IR and DM.


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