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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with hepatitis C virus (HCV) infection have a greater risk of developing type 2 diabetes mellitus. However, the mechanism of this association is unclear. In this study, we examined the potential defects in upstream insulin signaling pathways in liver specimens obtained from nonobese/nondiabetic subjects with HCV infection. Fasting liver biopsy specimens were obtained from 42 HCV-infected subjects and 10 non-HCV-infected subjects matched for age and body mass index. Liver tissues were exposed to insulin and examined for the contents and phosphorylation/activation status of the upstream insulin signaling molecules by immunoprecipitation and Western blot analysis. HCV infection resulted in a trend toward a 2-fold to 3-fold increase in insulin receptor (IR) and insulin receptor substrate (IRS)-1 contents when compared with non-HCV. In contrast, insulin-stimulated IRS-1 tyrosine phosphorylation was decreased by 2-fold in HCV-infected subjects compared with non-HCV-infected subjects (P <.05). The observed reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs. non-HCV). This was accompanied by a marked reduction in insulin-stimulated Akt phosphorylation without any alterations in mitogen-activated protein kinase (MAPK) phosphorylation. Cellular contents of the hepatic p85 subunit of PI3-kinase were comparable between HCV-infected and non-HCV-infected subjects. In conclusion, we found that (1). HCV infection leads to a postreceptor defect in IRS-1 association with the IR and (2). insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to insulin resistance, which leads to the development of type 2 diabetes mellitus in patients with HCV infection.
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PMID:Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. 1464 49

Past studies of the relation between hepatitis C virus (HCV) infection and type 2 diabetes conflict. The authors aimed to elucidate the relation by using a large community-based sample with a wide range of liver conditions. Between October 1997 and February 1998, 2,327 consecutive subjects (aged > or =35 years) were enrolled at the public health facility in Taiwan. Blood sugar, hepatitis B surface antigen, and antibody for HCV (anti-HCV) were tested. Abdominal sonography was performed on viral-hepatitis-positive subjects. In univariate analysis, older age, lower educational levels, sedentary work, body mass index of > or 25 kg/m2, and anti-HCV positivity were significantly associated with type 2 diabetes (p<0.05), but smoking, alcohol consumption, gender, and hepatitis B surface antigen status were not. In multivariate logistic regression, anti-HCV positivity was strongly associated with type 2 diabetes in subjects aged 35-49 years (odds ratio (OR)=3.3, 95% confidence interval (CI): 1.4, 8.0) and 50-64-years (OR=1.6, 95% CI: 1.1, 2.5). Sonographic evidence of fatty liver (OR=2.4, 95% CI: 1.2, 4.8) and chronic liver disease (OR=2.0, 95% CI: 1.0, 4.2) in anti-HCV-positive subjects was moderately associated with type 2 diabetes after age and gender adjustment. Data suggest that HCV infection is moderately associated with type 2 diabetes; the association was strongest for subjects aged 35-49 years and increased with severity of the liver condition.
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PMID:Community-based study of hepatitis C virus infection and type 2 diabetes: an association affected by age and hepatitis severity status. 1465

Nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV)-related liver disease are common in the general population, but their concurrence is 2- to 3-fold higher than would be expected by chance alone. In patients with chronic HCV infection, steatosis is attributable to a variable combination of the mechanisms considered to play a role in the pathogenesis of NAFLD--insulin resistance in the obese and in the lean subject--along with a direct effect of HCV on hepatic lipid metabolism that leads to triglyceride accumulation through inhibition of export proteins that are required for very low density lipoprotein (VLDL) assembly and secretion. Accumulating evidence suggests that steatosis contributes to the progression of fibrosis in HCV-related disease in a pattern similar to that observed in NAFLD. Potential mechanisms of this effect include the increased sensitivity of steatotic livers to oxidative stress and cytokine-mediated injury. Steatosis-related hepatic insulin resistance may also play a role through the profibrogenic effects of the compensatory hyperinsulinemia and provides a potential explanation for the association between HCV and type 2 diabetes mellitus. Indeed, an appreciation of the importance of fat in HCV has recently led to trials of adjuvant therapy for HCV directed at steatosis-associated disease mechanisms, with encouraging results reported for various modalities, including weight loss and antioxidants. Future therapy should be aimed at exploiting the interactions of HCV with host insulin and lipid metabolism, particularly in nonresponders to standard antiviral schedules.
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PMID:Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. 1476 95

Diabetes mellitus is a independent risk factor for the hepatitis C and for the hepatocellular carcinoma. Fatty liver is a obviously finding in patients with type 2 diabetes. It can develop steatofibrosis, steatohepatitis or liver cirrhosis. Steatohepatitis may be affected with weight reduction, metformin, rosiglitazon, or orlistat.
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PMID:[Diabetes mellitus and liver diseases]. 1530 36

Epidemiological studies have shown that obesity is a risk factor for hepatocellular carcinoma. Similar studies further indicate that diabetes is also a major risk factor. Both obesity and diabetes are frequently associated with nonalcoholic fatty liver disease, and case reports have shown progression of nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma. Although no study has clearly tied all of these variables together, it is likely that the association of hepatocellular carcinoma with obesity represents the progression of underlying nonalcoholic fatty liver disease to cirrhosis. The mechanism most likely involves replicative senescence of steatotic mature hepatocytes and compensatory hyperplasia of progenitor (oval) cells as a reaction to chronic injury due to ongoing nonalcoholic steatohepatitis and resultant hepatic fibrosis. Growth factors associated with chronic inflammation, type 2 diabetes, and DNA mutations as a result of lipid peroxidation probably play significant roles in clonal expansion and hepatocellular carcinoma progression. It remains unclear whether cirrhosis is a prerequisite for the development of hepatocellular carcinoma or whether hepatocellular carcinoma can develop in fatty liver in the absence of cirrhosis. However, well-documented case reports suggest that most cases of hepatocellular carcinoma arise in the setting of nonalcoholic steatohepatitis with cirrhosis. Whether therapy aimed at nonalcoholic fatty liver disease reduces the risk of hepatocellular carcinoma remains to be shown. Prophylactic measures and the role of cancer surveillance have not been adequately investigated, but current evidence suggests a risk for hepatocellular carcinoma in nonalcoholic steatohepatitis-related cirrhosis that rivals that of hepatocellular carcinoma in hepatitis C virus-related cirrhosis, particularly in older male patients.
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PMID:Obesity and hepatocellular carcinoma. 1550 9

Diabetic nephropathy (DN) is the number one cause of end-stage renal disease (ESRD) in the United States and is highly prevalent in African Americans. Since 1997, DN has been the number one cause of ESRD in African Americans. In African Americans, almost all DN is due to type 2 diabetes mellitus (T2DM), and nephropathy may affect female more than male patients. African Americans with T2DM are at increased risk for developing and having progression of DN. Glycemic control, development of albuminuria, family history of renal disease, and control of blood pressure are important risk factors for progression of DN. In addition, cigarette smoking, presence of hepatitis C, and use of thiazolinediones has an impact on renal survival in African Americans. Large vessel complications may be less frequent in African Americans with T2DM, when compared with white persons. Yet, cardiovascular disease and other microvascular complications are very common, and both are dependent on control of blood pressure. Achieving the recommended blood pressure of less than 130/80 mm Hg is essential but requires multiple antihypertensive medications, including an inhibitor of the renin-angiotensin system.
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PMID:Diabetic nephropathy in African-American patients. 1553 11

The hepatitis C virus (HCV) infection is a worldwide disease that is characterized by a preferential chronic evolution with mild to severe liver disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of these complications, HCV is frequently reported to complicate extrahepatic manifestations. Among those associated to HCV infection with a high degree of certainty, mixed cryoglobulinemia and its complications (skin, neurological, renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected patients. The other diseases include noncryoglobulinemic systemic vasculitis, splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda, sicca syndrome, and autoantibodies production. The extrahepatic manifestations that share mild-degree certainty of association with HCV infection include B-cell non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are more questionable for their eventual association with HCV and others (pulmonary fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case reports. Howerver, even in cases of tight association, the mechanisms through which HCV may promote or induce extrahepatic manifestations remain unclear and merit further investigations.
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PMID:Hepatitis C virus-associated extrahepatic manifestations: a review. 1555 28

Diabetes mellitus is the fifth leading cause of death in the United States; 17 million people are affected. Liver disease is one of the leading causes of death in persons with type 2 diabetes. The standardized mortality rate for death from liver disease is greater than that for cardiovascular disease. The spectrum of liver disease in type 2 diabetes ranges from nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma. The incidence of hepatitis C and acute liver failure is also increased. Nonalcoholic fatty liver disease is now considered part of the metabolic syndrome, and, with alcohol and hepatitis C, is the most common cause of chronic liver disease in the United States. Weight reduction and exercise are the mainstays of treatment for nonalcoholic fatty liver disease, but there are promising results with the new thiazolidinediones (pioglitazone and rosiglitazone) as well as metformin and 3-hydroxy-3-methylglutaryl coenzyme A inhibitors.
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PMID:Narrative review: hepatobiliary disease in type 2 diabetes mellitus. 1561 92

Recently, an epidemiological association between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (DM) has been reported in several studies, although many of them did not consider known risk factors in the pathogenesis of type 2 DM. The aim of this study was to assess the prevalence of type 2 DM among Brazilian HCV (+) and HCV (-) liver transplant candidates, analyzing known confounding factors for the development of type 2 DM. We conducted a cross-sectional study to evaluate the prevalence of type 2 DM among 106 liver transplant adult candidates, comparing 36 HCV (+) cirrhotic patients with 70 HCV (-) patients who developed cirrhosis from other causes. Type 2 DM was diagnosed after two consecutive fasting glucose values > or =126 mg/dL. The age, sex, and race distribution, severity of liver disease (Child-Pugh score), and family history of DM were similar in both groups, but the mean body mass index (BMI) was higher in the HCV (-) subjects (26.81 +/- 5.29 vs 24.0 +/- 4.71, P < .01) Most of the patients were Caucasians (70.75%). Type 2 DM was detected in 36.11% of HCV (+) group and in 25.71% of the HCV (-) (P = .27). A multivariate analysis revealed that family history of DM was the only significant independent predictor for DM (odds ratio = 2.55, 95% CI = 1.03 to 6.31, P = .04). In conclusion, our study did not show an association between HCV infection and Type 2 DM in Brazilian liver transplant candidates. It confirmed that the family history of DM was a determinant factor for the development of type 2 DM.
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PMID:Prevalence of type 2 diabetes mellitus in Brazilian liver transplant candidates: negative association with HCV status. 1562 Nov 46

Hepatic steatosis is the hallmark of nonalcoholic fatty liver disease (NAFLD), which is the consequence of multiple metabolic derangements among which insulin resistance plays a pivotal role. Steatosis is, also, a feature of hepatitis C virus (HCV) infection. However, in chronic hepatitis C, the prevalence of steatosis is 2.5-fold more elevated than that expected by a chance concurrence with NAFLD, suggesting that HCV may be implied in the development of steatosis. As observed in NAFLD, in patients infected with HCV genotype 1 steatosis is associated with an increased body mass index. On the other hand, in patients infected with genotype 3 the extent of steatosis strictly correlates with the viral load indicating that steatosis is mainly "virus-related". Regardless of the "metabolic" or "viral" etiology, hepatic steatosis in HCV contributes to the progression of liver fibrosis, to the development of hepatocellular carcinoma and to an impaired response to interferon treatment. Features such as obesity, insulin resistance and type 2 diabetes mellitus are shared by NAFLD and HCV-associated steatosis. In addition, HCV infection, directly or through steatosis, favors the development of type 2 diabetes mellitus. Hyperlipidemia is an independent predictor of the development of NAFLD, but not of HCV-associated steatosis. Arterial hypertension is common in nonalcoholic steatohepatitis patients, and HCV infection has recently been acknowledged as an independent risk factor for atherosclerosis. The role of iron in the progression of both NAFLD and HCV-associated steatosis remains controversial while lipoperoxidation and oxidative stress are pathogenic mechanisms shared by both. Some metabolic risk factors may be shared by both HCV-associated steatosis and NAFLD although the disease progression and pathophysiological background may be different. Preliminary data suggest that the therapeutic options for NAFLD may also be useful to improve HCV-associated steatosis.
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PMID:[Hepatitis C virus-associated and metabolic steatosis. Different or overlapping diseases?]. 1585 90


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