Mechanisms of increased insulin resistance in non‐cirrhotic patients with chronic hepatitis C virus infection

Maeno, Tadashi; Okumura, Akihiko; Ishikawa, Tetsuya; Kato, Koichi; Sakakibara, Fumihiko; Sato, Ken; Ayada, Minoru; Hotta, Nigishi; Tagaya, Tsuneaki; Fukuzawa, Yoshitaka; Kakumu, Shinichi

doi:10.1046/j.1440-1746.2003.03179.x

Cited by 78 publications

(59 citation statements)

References 32 publications

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“…Rather, IR in CHC seems to be due to direct virus-specific effects on insulin signaling. Thus, initial studies noted increased serum levels of TNF-α in subjects with CHC [66][67][68] or showed a correlation with IR [69] but did not adequately correct for potential confounders. A later well-controlled study compared 154 HCV-infected non-diabetic males with 75 matched uninfected controls [65] .…”

Section: Inflammation and Irmentioning

confidence: 99%

Molecular mechanisms of insulin resistance in chronic hepatitis C

Douglas

George²

2009

WJG

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It is now widely recognized that chronic hepatitis C (CHC) is associated with insulin resistance (IR) and type 2 diabetes, so can be considered a metabolic disease. IR is most strongly associated with hepatitis C virus (HCV) genotype 1, in contrast to hepatic steatosis, which is associated with genotype 3 infection. Apart from the well-described complications of diabetes, IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma. More recently, it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined. This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.

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Section: Inflammation and Irmentioning

confidence: 99%

Molecular mechanisms of insulin resistance in chronic hepatitis C

Douglas

George²

2009

WJG

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“…However, other studies have suggested that HCV may be directly involved in the development of type 2 DM or insulin resistance even in those without cirrhosis [8,[17][18][19] 491 HCV-infected persons over the age of 40 years in a nationwide cross-sectional study [11] and then in a longitudinal cohort study found that those with HCV infection were at increased risk for developing DM with increasing age and body mass index (BMI). Another nationwide crosssectional study dividing patients into young and old groups found an association of HCV and DM in those who were younger and had a family history of DM [20].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C is associated with type 2 diabetes mellitus in HIV‐infected persons without traditional risk factors

et al. 2007

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ObjectivesHepatitis C virus (HCV) monoinfection has been linked to type 2 diabetes mellitus (DM). We evaluated the effect of HCV on risk of DM in relation to traditional risk factors such as age, body mass index (BMI) and family history of DM in an HIV-infected population. MethodsThis was a retrospective, cross-sectional study of 1529 HIV-infected out-patients. An adjusted multivariate logistic regression was performed to assess the effect of HCV seropositivity on DM stratified by low and high propensity for DM based on age, BMI and family history. ResultsRace, age, BMI, family history and HCV were associated with DM. Use of protease inhibitors (PIs) was not associated with DM, but HIV/HCV-coinfected patients were less likely to be on PIs than those with HIV infection alone. In a multivariate analysis controlled for race, the association between HCV and DM was stronger in lean, young patients without a family history of DM; the low-risk group. No association between HCV and type 2 DM was seen in patients who were older or overweight or had a family history of DM; the high-risk group. PI use did not affect the association between HCV and DM. ConclusionsHepatitis C is an independent risk factor for type 2 diabetes in young, lean, HIV-infected patients. HIV-infected patients with HCV infection, regardless of whether they are on PIs, should be carefully screened for DM even if traditional risk factors for DM are not present.Keywords: diabetes mellitus, hepatitis C virus, HIV, protease inhibitors, risk factors IntroductionType 2 diabetes mellitus (DM) is a common comorbid condition in those coinfected with HIV and the hepatitis C virus (HCV). Multiple factors may lead to the development of DM in HIV-infected persons. First, patients infected with HIV but not HCV who are taking protease inhibitors (PIs) are at increased risk for developing DM [1][2][3]. Secondly, longer duration of HIV-positive survival as a result of highly active antiretroviral therapy (HAART) leads to an older population which may contribute to the higher prevalence of DM, especially in those with HIV/HCV coinfection [4]. HCV itself has been linked to type 2 DM [5][6][7][8][9][10][11], and the higher prevalence of HCV in HIV-infected persons may also contribute to the increased prevalence of DM in the HIV-infected population [12].The association of HCV and type 2 DM is complex, with some studies suggesting that the higher prevalence of DM is a result of more severe liver disease in both the HCV-and hepatitis B virus (HBV)-infected groups [7,9,[13][14][15][16]. However, other studies have suggested that HCV may be directly involved in the development of type 2 DM or insulin resistance even in those without cirrhosis [8,[17][18][19] 491 HCV-infected persons over the age of 40 years in a nationwide cross-sectional study [11] and then in a longitudinal cohort study found that those with HCV infection were at increased risk for developing DM with increasing age and body mass index (BMI). Another nationwide crosssectional study dividing patients into yo...

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“…Many reports state that diabetes is associated with persistent HCV infection (22,23). Because she had received highdose corticosteroid therapies, we are not certain about the cause-effect relationship, but the possibility remains.…”

Section: Discussionmentioning

confidence: 99%

Sjoegren's Syndrome Associated with Chronic Hepatitis C, Severe Thrombocytopenia, Hypertrophic Cardiomyopathy, and Diabetes Mellitus

et al. 2005

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A 74-year-old woman with Sjögren's syndrome and chronic hepatitis C (CHC) was admitted to our hospital in October 2003 for treatment of diabetes mellitus. She had the past history of recurrent thrombocytopenia, which was proven to be due to peripheral destruction. Although she had been diagnosed with hypertrophic cardiomyopathy (HCM) for 2 years, she had never felt palpitation. She suddenly died probably of fatal arrhythmia related to HCM during the last hospitalization.

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Mechanisms of increased insulin resistance in non‐cirrhotic patients with chronic hepatitis C virus infection

Abstract: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.

Cited by 78 publications

References 32 publications

Molecular mechanisms of insulin resistance in chronic hepatitis C

Molecular mechanisms of insulin resistance in chronic hepatitis C

Hepatitis C is associated with type 2 diabetes mellitus in HIV‐infected persons without traditional risk factors

Sjoegren's Syndrome Associated with Chronic Hepatitis C, Severe Thrombocytopenia, Hypertrophic Cardiomyopathy, and Diabetes Mellitus

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