Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance

Shintani, Yoshizumi; Fujie, Hajime; Miyoshi, Hideyuki; Tsutsumi, Takeshi; Tsukamoto, Kazuhisa; Kimura, Satoshi; Moriya, Kyoji; Koike, Kazuhiko

doi:10.1053/j.gastro.2003.11.056

Cited by 703 publications

(556 citation statements)

References 40 publications

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“…A Spanish cross-sectional study found an OR of about 4 for having type II diabetes or impaired fasting glucose among patients with HCV-related chronic hepatitis compared to those with non-HCV chronic hepatitis (Lecube et al, 2004) and a USA cohort study showed that among people at high risk for diabetes, those with HCV infection were more than 11 times as likely as those without HCV infection to develop diabetes (Mehta et al, 2003). Experiments on transgenic mice have provided evidence for the contribution of HCV in the development of insulin resistance in HCV infection, which eventually leads to type II diabetes (Shintani et al, 2004). Overall, epidemiologic and biological data both suggest that the association between HCV infection and diabetes is real and appears to be causally linked, at least in predisposed individuals (older and overweight), as recently reviewed (Mehta et al, 2001;.…”

Section: Diabetes and Hepatocellular Carcinomamentioning

confidence: 99%

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

et al. 2006

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Hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol consumption are major causes of hepatocellular carcinoma (HCC) worldwide. We performed a systematic review of epidemiologic studies carried out on HCC aetiology in Southern Europe, an area with an intermediatehigh prevalence of these agents as well as of putative risk factors such as tobacco smoking, diabetes and obesity. To retrieve the articles, we performed a Medline search for titles and abstracts of articles. After the Medline search, we reviewed the papers and reference lists to identify additional articles. A synergism between HCV infection and HBV infection, overt (hepatitis B virus antigen (HbsAg) positivity) or occult (HBsAg negativity with presence of HBV DNA in liver or serum), is suggested by the results of some studies. The pattern of the risk for HCC due to alcohol intake shows a continuous dose-effect curve without a definite threshold, although most studies found that HCC risk increased only for alcohol consumption above 40-60 g of ethanol per day. Some evidence supports a positive interaction of alcohol intake probably with HCV infection and possibly with HBV infection. A few studies found that coffee has a protective effect on HCC risk due to various risk factors. Some data also support a role of tobacco smoking, diabetes and obesity as single agents or preferably cofactors in causing HCC. In countries with a relatively high alcohol consumption and intermediate levels of HCV and HBV infections (1-3% of population infected by each virus), such as Mediterranean countries, the three main risk factors together account for about 85% of the total HCC cases, leaving little space to other known risk factors, such as haemochromatosis, and to new, still unrecognised, factors as independent causes of HCC.

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Section: Diabetes and Hepatocellular Carcinomamentioning

confidence: 99%

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

et al. 2006

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“…Hence, glucose intolerance is common in patients with liver cirrhosis of whatever aetiology, and around 20% of cirrhotic patients have overt diabetes [3]. Chronic hepatitis C virus (HCV) infection is well known to be associated with increased risk of type 2 diabetes [4][5][6][7][8][9][10]. This risk association is independent of the presence of cirrhosis [11,12], and has been hypothesised to be mediated through insulin resistance and chronic inflammation [12].…”

Section: Introductionmentioning

confidence: 99%

Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients

et al. 2006

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Aims/hypothesis: We examined the association between chronic hepatitis B virus (HBV) infection and clinical outcomes in a consecutive cohort of Chinese patients with type 2 diabetes. Subjects, materials and methods: Between 1995 and 1999, 2,838 type 2 diabetes patients underwent comprehensive assessments and blood screening for hepatitis B surface antigen (HBsAg). The risk of occurrence of cardiovascular events and end-stage renal disease (defined as need for dialysis, doubling of serum creatinine or serum creatinine ≥500 μmol/l) was compared between HBsAg-positive and HBsAg-negative groups. Results: At baseline, HBV-infected patients (n=286, 10.1%) were younger (51.0±11.5 vs 53.7±12.7 years, p=0.004), had earlier onset of diabetes (51.0±11.5 vs 53.7±12.7 years, p=0.001) and a higher frequency of retinopathy (28 vs 22%, p=0.03) than non-HBV-infected patients. After a median follow-up of 3.5 years (interquartile range: 1.7-5.9 years) and adjustment of age, glycaemic control and other potential confounding factors, HBV-infected patients were more likely to develop end-stage renal disease than non-HBV infected patients (8.7 vs 6.4%) with a hazard ratio of 4.5 (95% CI 1.1-18.6). The difference in the frequency of cardiovascular endpoints was not statistically significant. Conclusions: In Chinese type 2 diabetes patients, chronic HBV infection was associated with increased risk of end-stage renal disease, and this was independent of other potential confounding factors. Early identification of HBV status and close surveillance of renal function are important in patients with type 2 diabetes who are living in areas where HBV is endemic or who are at risk of chronic HBV infection.

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“…Hepatic steatosis, commonly observed in HCV genotype 3 infected patients, could be regarded as a risk factor for the development of insulin resistance. However, the presence of impaired insulin action before the onset of hepatic steatosis would appear to imply a secondary role for liver fat storage, as demonstrated by Shintani et al in a transgenic mouse model expressing the HCV core protein in the liver [58]. Another mechanism thought to be involved in insulin resistance in chronic hepatitis C is the pro-inflammatory cytokine profile observed during HCV infection.…”

Section: Viral Hepatitismentioning

confidence: 99%

“…Another mechanism thought to be involved in insulin resistance in chronic hepatitis C is the pro-inflammatory cytokine profile observed during HCV infection. The high intrahepatic levels of TNF-α in experimental animal models of HCV infection [59], as well as the high levels of circulating TNF-α in HCV-infected patients [11], could be involved in the altered insulin sensitivity by influencing the IR activity [48,58,60]. Whether HCV-related insulin resistance involves primarily the liver [58] or other peripheral effectors of insulin action, such as skeletal muscle and adipose tissue, is still a matter of debate.…”

Section: Viral Hepatitismentioning

confidence: 99%

Diabetes in chronic liver disease: from old concepts to new evidence

Picardi

D’Avola

Gentilucci

et al. 2006

Diabetes Metab. Res. Rev.

102

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SummaryThe liver is one of the principal organs involved in glucose metabolism together with skeletal muscle and adipose tissue. A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, but to date several questions remain unsolved. Altered glucose tolerance has been well described in alcoholic CLD, non-alcoholic fatty liver disease, chronic hepatitis C and portal hypertension. Moreover, insulin resistance is assuming an ever-growing importance in CLD; chronic hepatitis C has recently been proposed as a metabolic disease and insulin sensitivity as a predictive factor for liver fibrosis.CLD is also complicated by acquired growth hormone (GH) resistance, characterized by low concentrations of insulin-like growth factor-1 (IGF-1) with respect to normal or elevated GH levels. GH resistance in CLD is determined by several factors, including malnutrition, impaired liver function and reduced expression of hepatic GH receptors. We recently described the possible role of tumour necrosis factor-alpha (TNF-α) in blunting the hepatic response to GH in patients with chronic hepatitis C. The role of GH in impaired glucose metabolism is well known, and recent evidence suggests a receptor and/or post-receptor modulation of insulin signalling. Moreover, as in other chronic inflammatory conditions, pro-inflammatory cytokines may directly modulate the signal cascade that follows insulin binding to its receptor in the course of CLD.In this review, the proposed links between impaired glucose tolerance and CLD are analysed, special emphasis being focussed on the most recent findings concerning the interplay of chronic inflammation, GH resistance and insulin resistance.

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Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance

Cited by 703 publications

References 40 publications

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients

Diabetes in chronic liver disease: from old concepts to new evidence

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