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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 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-alpha) 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.
Diabetes Metab Res Rev
PMID:Diabetes in chronic liver disease: from old concepts to new evidence. 1650 76

Diabetes mellitus has been reported to have an increased prevalence and to be associated with more severe fibrosis in patients with chronic hepatitis C. We evaluated the prevalence of diabetes mellitus in patients with chronic hepatitis B or C as well as the possible association between presence of diabetes and extent of liver fibrosis. In total, 434 consecutive patients with histologically documented hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (n = 174) or chronic hepatitis C (n = 260) were studied. The relationships of diabetes and epidemiological, somatomorphic, laboratory and histological patient characteristics were evaluated. Liver histological lesions were blindly evaluated according to the Ishak's classification. Diabetes was present in 58 (13%) patients, without any difference between those with chronic hepatitis B (14%) or C (13%). Diabetes was observed significantly less frequently in patients with fibrosis score 0-2 (7.7%) than 3-4 (10.4%) than 5-6 (29.2%) (P < 0.001). The presence of diabetes was independently associated with higher gamma-glutamyl-transpeptidase (GGT) levels and more severe fibrosis or presence of cirrhosis (P < 0.001) as well as with presence of hepatic steatosis and increased serum triglycerides levels (P < 0.02). In the noncirrhotic patients, diabetes was significantly associated with older age and higher GGT levels, but not with the extent of fibrosis. In conclusion, diabetes mellitus is observed in more than 10% of patients with either HBeAg-negative chronic hepatitis B or chronic hepatitis C. The presence of diabetes is strongly associated with more severe liver fibrosis, but such an association may be related to the high prevalence of diabetes in patients with cirrhosis.
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PMID:Diabetes mellitus in chronic hepatitis B and C: prevalence and potential association with the extent of liver fibrosis. 1663 60

The aim of our study was to assess the long-term liver histology in renal transplant patients infected with hepatitis C virus (HCV) who were treated with a cyclosporine-based regimen. Among 55 anti-HCV+/RNA+ patients, liver biopsies (LB) were requested every 3 to 4 years after transplantation: two LBs (n=55); three LBs (n=44); four LBs (n=10). Overall, the rate of liver fibrosis progression was 0.07+/-0.03 Metavir U/y. Only three patients out of 55 (5.4%) developed cirrhosis. Liver fibrosis remained stable throughout follow-up in 21 patients; increased in 21 patients; and improved in the remaining 13 patients. The incidence of posttransplant diabetes mellitus was low (9%). We concluded that HCV infection is not harmful to liver histology in more than 50% of renal transplant patients with grafts functioning more than 6 years. Cyclosporine might have beneficial effects on the natural course of HCV infection after renal transplantation.
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PMID:Does cyclosporine have a beneficial effect on the course of chronic hepatitis C infection after renal transplantation? 1679 94

We carried out a retrospective review of infants with biliary atresia splenic malformation (BASM). We found that 56 infants (10.2%) met the criteria for inclusion from a series of 548 infants (from January 1977 to December 2004). Syndromic infants were more likely to be female (P = .04) and to have a higher incidence of antenatal pathology (specifically maternal diabetes; 12.5% vs 1.2%; P < .0001). Situs inversus was noted in 21 (37%) and cardiac abnormalities in 25 (45%) infants. There were no differences in liver histology (eg, degree of liver fibrosis) or in the HLA genotype between BASM and nonsyndromic infants. Five-year and 10-year estimated native liver survival were 46% and 32%, respectively. There were 7 long-term survivors with their native liver and a follow-up of more than 10 years; all were anicteric. BASM is a distinct subgroup, with an implied onset during the embryological phase of organ development.
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PMID:The biliary atresia splenic malformation syndrome: a 28-year single-center retrospective study. 1693 55

It is estimated that 43% of patients with nonalcoholic steatohepatitis (NASH) will progress to liver fibrosis or cirrhosis. Although NASH is more common in Hispanics, most studies have been conducted on Caucasians, and there is scarce information regarding ethnic differences in this disease. The aim of this study was to identify the independent predictors of cirrhosis in Hispanic patients with NASH. A retrospective case-control study was conducted on 80 patients with biopsy-proven NASH. Forty-two were Hispanic (study group) and 38 were Caucasians controlled for age and BMI (control group). Clinical, biochemical, and histologic features were analyzed for correlation with cirrhosis. There were no significant differences in demographic features between the two groups. In multivariate analysis, independent predictors of cirrhosis among Hispanic patients were age (OR, 1.07; 95% CI, 1.01-1.14) and AST/ALT ratio (OR, 10.56; 95% CI; 2.46-45.29), while independent predictors among non-Hispanic patients were age (OR, 1.085; 95% CI, 1.0-1.186), and diabetes mellitus (OR, 6.46; 95% CI, 1.19-35.07). In patients with NASH, predictors of cirrhosis varied according to ethnic background. Age was an independent predictor in both groups, however, AST/ALT ratio was found to be an independent predictor of cirrhosis only in Hispanic patients, and diabetes mellitus only in non-Hispanic patients.
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PMID:Predictors of cirrhosis in Hispanic patients with nonalcoholic steatohepatitis. 1695 1

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy-proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver-related (P = .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.
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PMID:Long-term follow-up of patients with NAFLD and elevated liver enzymes. 1700 14

We sought to investigate survival among kidney transplant candidates with varying degrees of liver fibrosis. We studied 108 patients with hepatitis C+ who underwent pre-kidney transplant liver biopsy (1992-2004). Eighteen patients had advanced fibrosis (bridging fibrosis or cirrhosis), and 90 had lesser degrees of fibrosis. Advanced fibrosis patients were younger and had lower prevalence of diabetes. Survival was similar between those with and without advanced fibrosis among all 108 patients (P = 0.92) and among the 58 patients who underwent kidney transplantation (P = 0.83). Fibrosis stage was associated with a 1.1 (0.72, 1.7; P = 0.65) adjusted hazards ratio for mortality among all 108 patients and a 0.64 (0.24, 1.73; P = 0.38) adjusted hazards ratio among the 58 patients who underwent kidney transplantation. These data support the premise that non-liver disease comorbidities are more important outcome determinants in this population. Kidney transplantation alone may be considered in patients with hepatitis C with compensated cirrhosis or bridging fibrosis.
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PMID:Effects of hepatitis C-induced liver fibrosis on survival in kidney transplant candidates. 1739 69

Nonalcoholic steatohepatitis (NASH) may cause progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Treatment, thus far, has been restricted to diet and weight loss, but without compelling results. In this study we aimed to evaluate the efficacy of orlistat therapy in obese patients with NASH. Fourteen obese patients with NASH underwent liver biopsy prior to and subsequent to 6 months treatment with orlistat (120 mg tid). Hepatic fat extension was graded as normal, mild, moderate, or severe. Hepatic fibrosis was scored on a scale from 0 to 4, with 0 denoting no fibrosis and 4, cirrhosis. Portal inflammation was scored as 0-3, with 0 = normal, 1 = mild, 2 = moderate, and 3 = severe inflammation. Fourteen patients had NASH associated with diabetes, hyperlipidemia, or obesity. Orlistat reduced fatty infiltration in 10 patients (70%; P<0.01), 3 of whom had normal liver fat content after treatment. Orlistat improved inflammatory activity by 2 grades in 28% and by 1 grade in 50% of patients and effected no change in 22% of patients. Five patients (35%) returned to normal inflammatory activity. Orlistat improved hepatic fibrosis by 2 grades in three patients (21%) and by 1 grade in seven patients (50%). There was no change in four patients (28%). Orlistat lowered aminotransferases levels, total cholesterol, triglycerides and low-density lipoprotein, respectively. Insulin resistance index and malonyl dialdehyde levels improved significantly after orlistat therapy, whereas HbAic remained unchanged. In conclusion, in obese patients with NASH, liver fibrosis and inflammation improved after therapy with orlistat.
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PMID:Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). 1740 56

Endothelin-1 (ET-1) is known to play an important role in hepatic fibrosis. ET-1 is also a mediator that is elevated in conditions such as insulin resistance, hyperglycemia, oxidative stress, and endothelial cell dysfunction. In this study, we investigated whether ET-1 has a role in determining the severity of liver fibrosis in NASH. Also, the relation between ALT levels, obesity, diabetes, and AST/ALT ratio and fibrosis and ET-1 level was sought. A total of 92 patients were enrolled in the study. The patients were categorized into three groups: group 1, patients with elevated transaminase levels who were diagnosed as NASH by liver biopsy (n=40); group II, patients with only hepatosteatosis determined by biopsy but having elevated transaminase levels (n=12); and group III, patients with hepatosteatosis observed by ultrasonography, having normal transaminase levels (n=40). The serum ET-1 level was measured by an appropriate ELISA kit for all patients. Mean serum ET-1 level was statistically significantly higher in the NASH group compared to the other two groups (15.56+/-4.63 vs 6.75+/-2.46 and 5.74+/-2.34 micromol/L; P < 0.01). Mean serum ET-1 levels in NASH patients with grade I, grade II, and grade IV fibrosis were 14.06+/-0.92, 17.70+/-2.32, and 20.40+/-1.40 micromol/L, respectively. None of the patients were identified as grade III fibrosis. It was found that the serum ET-1 level showed a statistically significant increase as fibrosis severity increased in NASH patients (P < 0.05). In conclusion, the serum ET-1 level is higher in NASH patients compared to patients having only steatosis. There appears to be a correlation between severity of fibrosis and serum ET-1 level in NASH patients. It has been found that NASH patients having a twofold increase in their ALT levels had higher ET-1 levels and a more severe grade of fibrosis.
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PMID:The serum endothelin-1 level in steatosis and NASH, and its relation with severity of liver fibrosis. 1742 33

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. It encompasses a wide spectrum of liver lesions, from pure steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma. Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can be considered a liver manifestation of the metabolic syndrome, its prevalence is high in obese people and in patients who have type 2 diabetes-insulin resistance is one of the key elements of the pathogenesis of NAFLD. This disease is often asymptomatic in the absence of decompensated cirrhosis, but should be suspected in patients with elevated aminotransferase levels or radiological evidence of a fatty liver or hepatomegaly. Liver fibrosis is associated with age over 50 years, obesity, diabetes and high triglyceride levels. Liver biopsy is the only way to assess the histologic features of necrotic inflammation and fibrosis that define nonalcoholic steatohepatitis and to determine its probable prognosis. The prognosis is good for pure steatosis, whereas the presence of necrotic inflammation is associated with a significant risk of progression to cirrhosis and, possibly, hepatocellular carcinoma. Lifestyle changes, such as dietary modifications and exercise, are recommended. To date, there have been very few randomized, placebo-controlled trials of drug treatments for NAFLD.
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PMID:Nonalcoholic fatty liver disease: from pathogenesis to patient care. 1751 90


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