Insulin resistance/β‐cell function and serum ferritin level in non‐diabetic patients with hepatitis C virus infection

Furutani, Masanori; Nakashima, Tomoki; Sumida, Yoshio; Hirohama, Akihisa; Yoh, Takaharu; Kakisaka, Yuko; Mitsuyoshi, Hironori; Senmaru, Hiroshi; Okanoue, Takeshi

doi:10.1034/j.1600-0676.2003.00841.x

Cited by 27 publications

(23 citation statements)

References 22 publications

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“…To our knowledge, this is the first report that describes the relationship between insulin resistance and Zn deficiency in patients with CH-C. Previously, Furutani and colleagues revealed that insulin resistance was characterized by iron accumulation in the liver (19). We confirmed the correlation between insulin resistance and iron overload in patients with ch-c and postulated that iron overload may derive from Zn deficiency.…”

Section: Discussionsupporting

confidence: 75%

“…Zn deficiency has been shown to result in attenuation of antioxidative properties and thereby a significant elevation in the serum ferritin level, which corresponds to iron accumulation in the liver. iron overload in the liver eventually evokes insulin resistance (19), as well as necroinflammation (30) in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…impaired signaling of the insulin receptor substrate (irS) by the hcV core protein is considered to trigger insulin resistance in patients with hcV-related cld (14). previous studies revealed that insulin resistance is significantly associated with body mass index (BMI) (15), hepatic steatosis (16), hepatic fibrosis (17,18) and/or iron overload (19) in patients with chronic hepatitis c (ch-c).…”

Section: Introductionmentioning

confidence: 99%

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Insulin resistance derived from zinc deficiency in non-diabetic patients with chronic hepatitis C

Himoto

Yoneyama

Deguch³

et al. 2010

Experimental and Therapeutic Medicine

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Abstract. chronic hepatitis c virus (hcV) infection frequently evokes metabolic abnormalities including insulin resistance. a decrease in serum zinc (Zn) levels is often observed in association with hepatic fibrosis. Zn also plays important roles in insulin secretion. however, little is known about the relationship between Zn deficiency and insulin resistance in patients with hcV-related chronic liver disease. the main purpose of this study was to examine the contribution of Zn deficiency to insulin resistance in patients with chronic hepatitis c (ch-c). Forty-eight non-diabetic patients with ch-c were enrolled. Serum alanine aminotransferase (alt), ferritin and Zn levels were examined in the enrolled patients with ch-c. insulin resistance was determined by the homeostasis model for assessment of insulin resistance (HOMA-IR). Zn deficiency was defined as serum Zn levels <65 µg/dl. Seven out of the 48 (15%) patients with CH-C fulfilled the criteria for Zn deficiency. Serum Zn levels were inversely correlated with serum ferritin levels (r=-0.364, p=0.0140). The values of HOMA-IR were positively linked to serum ferritin levels (r=0.299, p=0.0484). The mean value of HOMA-IR in the Zn deficiency group was significantly higher than that in the normal-range Zn group (3.76±0.66 vs. 2.08±1.35, p=0.0019). Serum ALT levels were also closely associated with serum ferritin levels (r=0.727, p<0.001). These findings were independent of HCV genotypes or loads of hcV-rna. Our data suggest that iron overload in patients with CH-C derives from Zn deficiency and thereby causes insulin resistance. IntroductionZinc (Zn) is an essential trace element that serves as the active center of approximately 300 enzymes and participates in physiological functions including immune function, neurosensory function, protein metabolism, wound healing and sexual function (1,2). Zn plays important roles as a growth co-factor, an immunomodulator and a cytoprotectant with antioxidant, antiapoptotic and anti-inflammatory effects (3,4). Therefore, Zn depletion results in numerous types of symptoms including taste disorder, hyperkeratotic skin change, wound healing disturbance and testicular dysfunction.Zn deficiency is also frequently observed in patients with chronic liver diseases (cld), including chronic hepatitis and liver cirrhosis (5-8). Serum Zn levels inversely correlate with the severity of hepatic fibrosis (7). Zn depletion in patients with liver cirrhosis is closely related to the progression of hepatic encephalopathy. Zn deficiency usually leads to a decrease in the activity of ornitine transcarbamylase, a key Zn-containing enzyme for the urea cycle. this consequently causes the accumulation of ammonia and seems to account for the pathogenesis of hepatic encephalopathy (9). Zn administration has favorable effects on the inhibition of hepatic fibrosis, activating collagenase, which belongs to a zinc-metallo-enzyme, and/or diminishing prolyl hydroxylase, which contributes to collagen synthesis (10). Zn supplementation also relieves hepatic ence...

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin resistance derived from zinc deficiency in non-diabetic patients with chronic hepatitis C

Himoto

Yoneyama

Deguch³

et al. 2010

Experimental and Therapeutic Medicine

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“…Insulin resistance, a precursor to the development of type 2 DM, has been shown to be higher in HIV/HCV-coinfected patients and HCVmonoinfected controls compared with HIV-monoinfected patients [17]. HCV-monoinfected patients without cirrhosis have also been shown to have insulin resistance, which increases with fibrosis and may be mediated by cytokines [18,[29][30][31]. A biologically plausible mechanism for insulin resistance in HCV infection was shown in a transgenic murine model that expressed HCV core protein.…”

Section: Discussionmentioning

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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“…Na hepatite C diversos estudos têm demonstrado a associação entre RI e níveis elevados de ferritina, mesmo quando pacientes diabéticos são excluídos da análise (18,19) . Entretanto, tem sido observado que a ferritina medida no sangue periférico está associada à presença de síndrome metabólica, tanto na população geral quanto entre diabéticos (30) .…”

Section: Mecanismos De Ri Na Hepatite Cunclassified

Importância da resitência insulínica na hepatite C crônica

Parise

Oliveira

2007

Arq. Gastroenterol.

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RESUMO -Objetivo -Revisar a importância da resistência insulínica no desenvolvimento da hepatite C crônica e sua interferência na resposta ao tratamento antiviral de pacientes infectados pelo vírus da hepatite C. Fonte de dados -Revisão bibliográfica de trabalhos publicados pelo MEDLINE e dados dos próprios autores. Síntese de dados -Nos últimos anos, grande número de publicações tem demonstrado importante associação entre resistência insulínica e hepatite C crônica. Aumento na prevalência de diabetes mellitus tipo 2, desenvolvimento de esteatose hepática (principalmente nos pacientes com infecção pelo genótipo não-3), progressão mais rápida da doença e redução na taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina, têm sido todos associados à presença de resistência insulínica nos pacientes infectados pelo vírus da hepatite C. A produção aumentada de fator de necrose tumoral pelo core do vírus da hepatite C é o principal mecanismo responsável pelo aparecimento da resistência insulínica. O fator de necrose tumoral afetaria a fosforilação do substrato do receptor de insulina diminuindo a captação de glicose e acarretando hiperinsulinemia compensatória. Aumento da siderose hepática e alterações dos níveis circulantes das adipocitocinas podem ter efeito adicional sobre a sensibilidade à insulina na hepatite C crônica. Conclusões -O diagnóstico e o tratamento da resistência insulínica nesses pacientes podem não só evitar o aparecimento das complicações, mas também prevenir a progressão da doença e, possivelmente, aumentar a taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina. DESCRITORES -Hepatite C crônica. Fígado gorduroso. Cirrose hepática. Resistência à insulina. Diabetes mellitus tipo 2. Interferons.A resistência à ação da insulina tem papel fundamental no aparecimento da síndrome metabólica. No tecido periférico dependente de insulina, ocorre um defeito intracelular pós-receptor na sinalização da insulina (Figura 1). Há bloqueio na fosforilação em tirosina dos substratos protéicos dos receptores de insulina (IRS), o que impede a transativação do GLUT 4 e, conseqüentemente, a entrada da glicose para o interior da célula. Isso faz com que maiores quantidades de insulina sejam secretadas pelas células β pancreáticas, criando um estado de hiperinsulinemia compensatória. Esse excesso de insulina resultante consegue, durante certo tempo, manter a glicemia dentro dos níveis da normalidade, mas acaba determinando importantes alterações em todo organismo. A mais conhecida é a extensiva deposição centrípeta da gordura corporal, conhecida como obesidade central ou visceral, onde ocorre grande aumento da gordura abdominal, em detrimento dos membros. Outros efeitos incluem o aumento da pressão arterial e dos níveis séricos de triglicérides e redução dos valores de HDL colesterol, com ou sem hiperglicemia. A presença de três ou mais dessas manifestações caracteriza a síndrome metabólica ou síndrome de resistência insulínica (64,72) .O estudo da re...

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Insulin resistance/β‐cell function and serum ferritin level in non‐diabetic patients with hepatitis C virus infection

Cited by 27 publications

References 22 publications

Insulin resistance derived from zinc deficiency in non-diabetic patients with chronic hepatitis C

Insulin resistance derived from zinc deficiency in non-diabetic patients with chronic hepatitis C

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

Importância da resitência insulínica na hepatite C crônica

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