Hepatitis C, metabolic syndrome, and inflammatory markers: Results from the Third National Health and Nutrition Examination Survey [NHANES III]

Abstract

Studies have shown that hepatitis C (HCV) is associated with type 2 diabetes mellitus (DM2) possibly due to insulin resistance and inflammation. Metabolic syndrome is a risk factor for DM2. Our objectives were to assess the relationship between HCV and metabolic syndrome and inflammatory markers. We used data from The Third National Health Nutrition and Examination Survey (NHANES-III). We excluded pregnant women, subjects with diabetes, those taking non-steroidal anti-inflammatory drugs, and those diagnosed with concomitant infection. We analyzed the data controlling for demographic variables, body mass index, use of contraceptives, had arthritis, and had gout. Among the 10,383 subjects, 2.3% had HCV and 16.7% had metabolic syndrome using the ATP III criteria. After controlling for the confounders, HCV was not associated with metabolic syndrome but associated with HOMA insulin resistance and inflammatory marker ferritin. Among subjects with both HCV and metabolic syndrome, the adjusted HOMA insulin level was higher than those without HCV and metabolic syndrome. In addition, the serum ferritin level was a strong predictor of HOMA insulin resistance. In clinical practice, serum ferritin can be obtained along with routine blood tests in any laboratory, and it has a potential to be a surrogate marker of insulin resistance in people with HCV and metabolic syndrome.

Introduction

Over four million Americans are infected with the hepatitis C virus (HCV), 85% of whom will develop chronic active hepatitis [1]. Chronic HCV infection progresses to the development of liver inflammation, fibrosis and in at least 20% of the cases, cirrhosis [2]. Many studies have shown an association between hepatitis C and type 2 diabetes mellitus (DM2) [3], [4], [5], [6], [7], [8], [9], [10]. The major proposed mechanisms for HCV-related diabetes mellitus have included direct pancreatic beta cell destruction by HCV, autoimmune beta cell damage, increased iron stores, non-alcoholic fatty liver disease, development of insulin deficiency and insulin resistance [1], [11], [12], [13]. Molecular studies documented that an inflammatory process is responsible for an insulin resistant state in those with HCV, thus leading to a predisposition for developing type 2 diabetes mellitus [14], [15], [16], [17], [18]. Other studies have shown that the prevalence of insulin resistance is higher in non-diabetic patients with chronic hepatitis C and found that insulin resistance is associated with a higher rate of fibrosis progression [19].

Metabolic syndrome is a risk factor for diabetes mellitus. Subjects with metabolic syndrome have higher rates of insulin resistance and therefore are at a higher risk of developing type 2 diabetes mellitus [20], [21], [22], [23]. According to the National Cholesterol Education Program Adult Treatment Panel III (ATP III), it is estimated that one-quarter of US adults 20 years or older meet the diagnostic criteria for metabolic syndrome [20]. This study also showed ethnic differences in the prevalence of metabolic syndrome ranging from a low of 13.9% in African-American men to a high of 27.2% in Mexican-American women, establishing the critical importance of studying this phenomenon in ethnic minorities, where rates of hepatitis C and type 2 diabetes mellitus are high.

Studies have shown an association between the metabolic syndrome and inflammatory markers such as C-reactive protein, fibrinogen, white blood cell count and ferritin [24], [25]. Other studies demonstrated that people with metabolic syndrome have a low-grade inflammation that subjects them to an increased risk for cardiovascular disease and DM2 [17]. These studies have suggested a relationship among hepatitis C, insulin resistance, and the metabolic syndrome, but few studies are available on the relationship between hepatitis C and inflammatory markers among subjects with metabolic syndrome. Using data from the the Third National Health and Nutrition Examination Survey (NHANES III), we examined the relationship between hepatitis C and metabolic syndrome. In addition, we studied the association between hepatitis C and inflammatory markers in subjects with metabolic syndrome.