Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study aimed to elucidate the relationship of type 2 diabetes, other known risk factors, and primary hepatocellular carcinoma (HCC) in countries with a high prevalence of hepatitis infection. We followed a prospective cohort of 54,979 subjects who participated in the Keelung Community-Based Integrated Screening program between 1999 and 2002. A total of 5,732 subjects with type 2 diabetes cases were identified at enrollment on the basis of fasting blood glucose level, and a total of 138 confirmed HCC cases were identified either through two-stage liver cancer screening or linkage with the National Cancer Registry. The independent effect of type 2 diabetes on the incidence of HCC and the interaction between type 2 diabetes and hepatitis infection or lipids profile were assessed using the Cox proportional hazards regression model. After controlling for age, sex, hepatitis B virus (HBV), hepatitis C virus (HCV), smoking, and alcohol consumption, the association between type 2 diabetes and incidence of HCC (excluding 33 prevalent cases identified at enrollment) was modified by HCV status and cholesterol level. The associations were only statistically significant (adjusted hazard ratio [HR] = 2.08 [1.03-4.18]) for being HCV negative and for having hypercholesterolemia (adjusted HR = 2.81 [1.20-6.55]). These statistically significant findings remained even excluding cases of diabetes newly diagnosed at enrollment. In conclusion, in an area with a high prevalence of hepatitis virus infection, type 2 diabetes increases the risk of developing HCC in those who are HCV negative or have a high level of total cholesterol.
 ...
PMID:Type 2 diabetes and hepatocellular carcinoma: A cohort study in high prevalence area of hepatitis virus infection. 1713 79

In the last 15 years evidence has been accumulating suggesting that hepatic steatosis may be the starting point for a progressive liver disease. Nonalcoholic steatosis (nonalcoholic fatty liver disease, NAFLD) is now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma. Liver disease of other etiology, namely hepatitis C virus, may interact with NAFLD, although the underlying mechanism(s) have not been fully elucidated. Type 2 diabetes mellitus, obesity and dyslipidemia are the principal factors associated with NAFLD, which is now considered the hepatic expression of metabolic syndrome (MS). Several studies have dealt with the relationship of NAFLD and MS, the risk of liver disease associated with the classical features of MS, the importance of insulin resistance as the common soil of different diseases. We still need to clarify the mechanism(s) responsible for liver disease progression from pure fatty liver, to steatohepatitis and to cirrhosis, and the reason(s) why only a few NAFLD cases progress to terminal liver failure while others (the majority) will have a cardiovascular outcome. The epidemics of obesity and diabetes of Western countries is expected to produce a significant increase of metabolic liver disease in the next years. Prevention and intervention programs based on lifestyle are therefore mandatory to reduce the burden of metabolic liver disease.
 ...
PMID:Nonalcoholic fatty liver disease and the metabolic syndrome. 1677 54

Type 2 diabetes mellitus (DM) has emerged as the commonest cause of end-stage renal disease. Haemodialysis (HD) treatment constitutes a high-risk environment for the transmission of hepatitis C virus (HCV). The aim of this study was to establish a potential relationship between type 2 DM and HCV infection in HD patients. Of the 267 HD patients, 67 (25.1%) had type 2 DM and 200 (74.9%) were with diverse aetiology for end-stage renal disease. The serum markers of HCV infection were tested by a second-generation enzyme-linked immunosorbent assay test for antibodies and by qualitative reverse-transcription polymerase chain reaction technique for viral RNA. The overall prevalence of anti-HCV antibodies and HCV RNA was found to be 12.7% (34/267) and 10.1% (27/267), respectively. Patients with type 2 DM were found to have a higher HCV prevalence compared with non-diabetic patients [20.8% (14/67) vs. 10% (20/200)] (p < 0.05). The mean period on dialysis of anti-HCV-positive patients with type 2 DM was shorter than that observed for anti-HCV-positive non-diabetic patients (43.9 +/- 9.8 months vs. 59.7 +/- 28.4 months) (p < 0.05). This study has shown that although the period on dialysis of diabetic patients are shorter than non-diabetic patients, the prevalence of HCV in HD patients with type 2 DM is higher than that detected in non-diabetic HD patients.
 ...
PMID:Seroprevalence of hepatitis C in patients with type 2 diabetes mellitus and non-diabetic on haemodialysis. 1680 51

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.
 ...
PMID:Hepatitis C, metabolic syndrome, and inflammatory markers: results from the Third National Health and Nutrition Examination Survey [NHANES III]. 1691 55

Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARgamma receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA < or = 2 than patients with HOMA > 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 microU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.
 ...
PMID:Insulin resistance and hepatitis C. 1713 67

The hepatitis C virus (HCV) core protein is a component of nucleocapsids and a pathogenic factor for hepatitis C. Several epidemiological and experimental studies have suggested that HCV infection is associated with insulin resistance, leading to type 2 diabetes. We have previously reported that HCV core gene-transgenic (PA28gamma(+/+)CoreTg) mice develop marked insulin resistance and that the HCV core protein is degraded in the nucleus through a PA28gamma-dependent pathway. In this study, we examined whether PA28gamma is required for HCV core-induced insulin resistance in vivo. HCV core gene-transgenic mice lacking the PA28gamma gene (PA28gamma(-/-)CoreTg) were prepared by mating of PA28gamma(+/+)CoreTg with PA28gamma-knockout mice. Although there was no significant difference in the glucose tolerance test results among the mice, the insulin sensitivity in PA28gamma(-/-)CoreTg mice was recovered to a normal level in the insulin tolerance test. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS1), production of IRS2, and phosphorylation of Akt were suppressed in the livers of PA28gamma(+/+)CoreTg mice in response to insulin stimulation, whereas they were restored in the livers of PA28gamma(-/-)CoreTg mice. Furthermore, activation of the tumor necrosis factor alpha promoter in human liver cell lines or mice by the HCV core protein was suppressed by the knockdown or knockout of the PA28gamma gene. These results suggest that the HCV core protein suppresses insulin signaling through a PA28gamma-dependent pathway.
 ...
PMID:Involvement of the PA28gamma-dependent pathway in insulin resistance induced by hepatitis C virus core protein. 1713 26

The liver plays a unique role in controlling carbohydrate metabolism by maintaining glucose concentrations in a normal range. This is achieved by a tightly regulated system of enzymes and kinases regulating either glucose breakdown or synthesis in hepatocytes. This process is under the control of glucoregulatory mediators among which insulin plays a key role. In type 2 diabetes, as well as in liver disease, alterations in hepatic glucose metabolism like an increased post-absorptive glucose production together with diminished glucose uptake following carbohydrate ingestion occur, implying insulin resistance as a central pathological principle. Knowledge of the processes involved in maintaining glucose homeostasis as well as insulin resistance is a prerequisite to develop new therapeutic approaches in diabetes as well as in liver disease. In the recent years, genetically-altered mouse models that have helped to identify enzymes, transcription factors and mediators that are essential for maintaining glucose homeostasis in the liver and provide a valuable tool to study carbohydrate metabolism in liver disease. In this current review, genetically manipulated animals either overexpressing or lacking key gluconeogenic enzymes, hepatic transcription factors, IGF-1, hepatic insulin receptors, adipokines and hepatitis C core antigen will be discussed in the context of human disease.
 ...
PMID:Carbohydrate metabolism and the liver: actual aspects from physiology and disease. 1723 21

The temporal relation of hepatitis C virus (HCV) infection to the development of type 2 diabetes remains unknown. The authors followed 4,958 persons aged > or =40 years without diabetes (3,486 seronegative, 812 anti-HCV+, 116 with hepatitis B virus/HCV coinfection, and 544 hepatitis B surface antigen (HBsAg)+) from a community-wide cohort in southern Taiwan for 7 years (1997-2003) to study the risk of diabetes associated with HCV infection. A total of 474 participants developed diabetes. The 7-year cumulative incidence was 7.5% for HBsAg+, 8.6% for seronegative, 14.3% for anti-HCV+, and 14.7% for coinfected participants. Compared with HCV- persons, HCV+ persons had a higher cumulative incidence of diabetes (log-rank test, p < 0.0001). A multivariate Cox proportional hazards model showed that anti-HCV+ (hazard ratio = 1.7, 95% confidence interval: 1.3, 2.1), coinfection (hazard ratio = 1.7), overweight, obesity, and increasing age were significantly associated with diabetes (p < 0.05). Gender, educational level, HBsAg+ status, alcohol consumption, and smoking were not significant. After stratification by age and body mass index, the risk ratio for diabetes in anti-HCV+ participants increased when age decreased and body mass index levels increased (p < 0.001). Results show that HCV infection is an independent predictor of diabetes, especially for anti-HCV+ persons who are younger or have a higher body mass index.
 ...
PMID:Hepatitis C virus infection and the development of type 2 diabetes in a community-based longitudinal study. 1822 96

Worldwide approximately 200 million people are chronically infected with hepatitis C virus (HCV). Chronic HCV infection represents the leading cause of liver cirrhosis and the main indication for liver transplantation in the western world. In addition, chronic HCV infection is associated with numerous clinical manifestations, including type 2 diabetes. An obvious and frequently suggested explanation for the connection between HCV infection and type 2 diabetes is that cirrhosis by itself causes insulin resistance. However, the prevalence of type 2 diabetes in HCV cirrhosis is higher than in HBV cirrhosis (23.6% vs 9.4%). This suggests that HCV infection by itself can lead to insulin resistance and predispose to the onset of type 2 diabetes. First, HCV core protein induces hepatic steatosis by inhibition of microsomal triglyceride transfer protein and hepatic steatosis causes insulin resistance. Secondly, HCV core protein inhibits, through elevation of TNF-alfa and other factors, the insulin-signalling pathways causing insulin resistance. Moreover, recent data strongly suggest that insulin resistance is an important predictor of poor response to antiviral therapy in chronic hepatitis patients treated with peginterferon plus ribavirin.
 ...
PMID:Hepatitis C and insulin resistance: mutual interactions. A review. 1754 92

We used available studies to answer two clinically relevant questions, i.e. whether those with type 2 diabetes should undergo hepatitis C virus screening and whether hepatitis C virus positive individuals should be screened for diabetes. Four reasons argue against the hypothesis of screening diabetics for hepatitis C virus. First, although it induces insulin resistance, hepatitis C virus is not directly diabetogenic. Second, the clinical phenotype of hepatitis C virus-associated type 2 diabetes might be a clue to target the specific diabetic population to be screened. Third, diabetic patients are expected to be poor responders to antivirals and evidence that this might result in recovery from type 2 diabetes is insufficient. Fourth, no econometric data are available in the specific subset of those with type 2 diabetes. Case finding of type 2 diabetes in those with hepatitis C virus infection, in contrast, might be considered in those patients with type 2 diabetes who have cirrhosis, in whom--due to increased prevalence and severity of hepatic encephalopathy--diabetes is associated with increased mortality. Preliminary evidence suggests that the prognosis of cirrhosis might benefit from improved glycemic control and thus from earlier diagnosis of type 2 diabetes. Finally, studies are needed to ascertain the most cost-effective strategy of case-finding type 2 diabetes among those who are hepatitis C virus-infected. In conclusion, available data enabled us to answer the two questions. Hepatitis C virus screening should best be restricted to those (lean) diabetic patients with (advanced) liver disease. Glucose tolerance testing should best be performed in those with hepatitis C virus-related cirrhosis. However, additional studies are needed to support the cost-effectiveness of our conclusions.
 ...
PMID:HCV and diabetes. A two-question-based reappraisal. 1761 Nov 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>