Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance (IR), glucose intolerance and diabetes mellitus are commonly associated with cirrhosis. The exact pathogenetic mechanisms responsible are still unknown; however, they may be related to both hepatitis C virus itself and to liver injury. IR may be the earliest abnormality, which in the following years may progress to clinical diabetes mellitus. The aim of this study was to investigate the presence of IR by euglycaemic hyperinsulinemic clamp technique, in chronic hepatitis C patients. 15 patients and nine healthy controls without any known condition that may affect IR were enrolled to the study. Chronic hepatitis C was diagnosed by liver biopsy (hepatic activity index was also determined in 10 patients) and appropriate viral and biochemical tests. Eight patients were given interferon therapy, which had been stopped for at least 3 months before the study. Euglycaemic hyperinsulinemic clamp technique was performed as previously described and peripheral glucose utilisation rate, M value, was calculated in mg/kg/min by infusion of 40 IU/m2/min regular insulin. M value of the control group was significantly higher than that of chronic hepatitis C patients (M = 5.1+/-1 vs. 3.7+/-1; p = 0.004), which was consistent with IR in the patient group. There was no significant correlation between the M value and alanine aminotransferase, aspartate aminotransferase and hepatic activity index (p = 0.621, 0.549, 0.479, respectively). Our results suggest that IR is present in chronic hepatitis C patients; it is not directly related to hepatic injury, moreover, it may be associated with some component(s) inherent to hepatitis C virus.
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PMID:Insulin resistance in chronic hepatitis C. 1560 64

Non-alcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is a well-established cause for chronic liver disease. In most studies on NASH, elevation in alanine aminotransferase (ALT) is taken as one of the diagnostic criteria. However, the clinical and histological spectrum and natural history of NAFLD with normal ALT are not well explored. This study was planned to define the clinical spectrum and natural history of patients with NAFLD with normal ALT, and to compare them with NAFLD with abnormal ALT. A prospective study including 81 consecutive patients with ahistological diagnosis ofNAFLD was planned during the period from 1999 to 2003. Consecutive (n=81) patients with the histological diagnosis of NAFLD were included in the study. In all the patients, clinical, anthropometric, laboratory, histological and imaging features were noted at the baseline. All these patients were followed up regularly at 6-month intervals. Of the 81 cases, 25 patients (including 60% cirrhotics) had persistently normal enzyme, whereas 56 (including 23% cirrhotics) had abnormal ALT. Both the groups were comparable with respect to distribution of age, gender, ethnicity, clinical features, imaging features, histological severity and laboratory features; except a higher incidence of diabetes and higher occurrence of advanced liver disease at baseline in NAFLD with normal ALT. Natural history of NAFLD was better in patients without cirrhosis irrespective of baseline ALT levels than in patients with cirrhosis; except for a higher incidence of decompensation in cirrhotics with normal ALT. The entire clinical and histological spectrum of NAFLD is seen in patients with normal ALT and is not different from patients with abnormal ALT. In patients with diabetes and hepatomegaly in the absence of other obvious liver diseases, even normal ALT may not rule out advanced liver disease, and liver biopsy may be necessary to identify the severity of liver disease.
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PMID:Clinical spectrum and natural history of non-alcoholic steatohepatitis with normal alanine aminotransferase values. 1568 60

Clinical presentations of drug-induced liver injury (DILI) cover essentially the entire spectrum of known liver diseases. However, in the last 8 years the form of liver injury that has most frequently resulted in labeling restrictions is idiosyncratic hepatocellular injury leading to acute liver failure. This rare form of DILI has a characteristic clinical presentation that includes an acute onset after uneventful treatment with drug for weeks to months. Serum alanine aminotransferase rises to very high levels and the appearance of jaundice indicates a high mortality even if the therapy is discontinued. Drugs that can cause this type of injury almost always are associated with frequent (2-15% of all treated patients) and minor serum aminotransferase elevations. These elevations are believed to reflect true liver injury, but often reverse even if drug therapy is continued. The bases for this "adaptation" is not known, as is why some patients do not adapt and develop progressive liver injury. Understanding how drugs cause severe idiosyncratic hepatocellular toxicity has been frustrated by the lack of good preclinical models. Indeed, because these events occur so rarely, the vast majority of humans are not good models. Studies of genomic DNA from affected individuals should provide important insight but not the complete answer because environmental factors almost certainly contribute to individual susceptibility. The most fruitful approach may therefore lie in focused and well-controlled phenotype/genotype studies of the rare patients who have survived this type of injury. The National Institute of Diabetes and Digestive and Kidney Diseases of The National Institutes of Health has recently sponsored a cooperative agreement (UO1) to create a Drug Induced Liver Injury Network (DILIN). DILIN consists of University of Michigan, Indiana University, University of Connecticut, University of California, San Francisco, University of North Carolina, and Duke University. This network should provide heretofore missing resources required to address the problem.
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PMID:Idiosyncratic liver injury: challenges and approaches. 1580 49

The antidiabetic effect of the crude exopolysaccharides (EPS) produced from submerged mycelial culture of Phellinus baumii in streptozotocin (STZ)-induced diabetic rats was investigated. The produced EPS consisted of two different heteropolysaccharides and two proteoglycans. The food intake of the diabetic control rats (STZ) was increased by 28.1%, whereas body weight gain was reduced by 44.1% as compared to the nondiabetic animals (NC). The plasma glucose level in the EPS-fed rats (EPS) was substantially reduced by 52.3% as compared to the diabetic rats (STZ), which is the highest hypoglycemic effect among mushroom-derived materials documented in literature. The activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST) were significantly decreased by administration of P. baumii EPS, thereby exhibiting a remedial role in liver function. The significant increase in weights of liver, spleen, and kidney was observed in diabetic groups (both STZ and EPS) compared to NC. The results suggest that orally administrated P. baumii EPS exhibited considerable hypoglycemic effect in STZ-induced diabetic rats and that these EPS may be useful for the management of diabetes mellitus.
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PMID:Hypoglycemic effect of crude exopolysaccharides produced by a medicinal mushroom Phellinus baumii in streptozotocin-induced diabetic rats. 1585 May 99

The mechanisms linking obesity and inactivity to diabetes mellitus are unclear. Recent studies have shown associations of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) with diabetes. In a random sample of 3,789 British women aged 60-79 years, the authors examined the associations of obesity and physical activity with ALT and GGT (1999-2001). Both body mass index and waist:hip ratio were independently (of each other, physical activity, alcohol consumption, smoking, and childhood and adulthood social class) positively and linearly associated with ALT and GGT. In adjusted models, a one-standard-deviation increase in body mass index was associated with a 0.46-units/liter (95% confidence interval (CI): 0.16, 0.75) increase in ALT and a 2.14-units/liter (95% CI: 0.99, 3.30) increase in GGT. Similar results for a one-standard-deviation increase in waist:hip ratio were 13.96 (95% CI: 10.44, 17.48) for ALT and 39.44 (95% CI: 25.89, 52.98) for GGT. Frequency of physical activity was inversely and linearly associated with GGT in fully adjusted models, but the inverse association with ALT was attenuated towards the null after adjustment for body mass index and waist:hip ratio. Adjustment for ALT and GGT resulted in some attenuation of the strong linear associations of body mass index and waist:hip ratio with diabetes. These findings provide some support for the suggestion that the relation between obesity and diabetes is, at least in part, mediated by liver pathology.
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PMID:The associations of physical activity and adiposity with alanine aminotransferase and gamma-glutamyltransferase. 1590 29

Using data from the Third National Health and Nutrition Examination Survey (United States, 1988-1994), we compared clinical phenotypes of hepatitis C virus (HCV)-seropositive and seronegative adults aged 20-89 years with hyperglycemia (impaired fasting glucose (IFG) or type 2 diabetes, n=3566 including 86 with HCV). Seroprevalence was higher among younger persons (3.4% for ages 20-59 versus 0.9% for ages 60-89, p=0.002), while traditional correlates of diabetes (hypertension, coronary heart disease) were more prevalent among older persons (both comparisons, p<0.0001). To prevent confounding by age, younger and older persons were analyzed separately. In both age groups, HCV was associated with signs of hepatic impairment and B-cell clonal expansion (higher alanine aminotransferase (ALT) and serum globulin, lower total cholesterol and platelet count). Only among younger persons, however, was HCV also associated with a marker for advanced hepatic fibrosis (elevated serum ferritin) and absence of the classical diabetic phenotype (overweight, coronary heart disease). In addition, among younger persons, HCV was currently associated with family history of diabetes, positively in persons with diabetes and inversely in those with IFG, suggesting that family history of diabetes may serve as a cofactor for progression from HCV-associated IFG to diabetes.
Diabetes Res Clin Pract 2006 Jan
PMID:Hyperglycemia among persons with hepatitis C: not the classical diabetic phenotype. 1661 68

Hyperglycemia increases the generation of free radicals by glucose auto-oxidation, and the increment of free radicals may lead to liver cell damage. In this study, we tested the hypothesis that hyperglycemia-induced increases of serum liver enzymes among its physiological concentration would be inversely associated with serum antioxidant carotenoid level. Study subjects were 857 male and female Japanese who had received health examinations in 2003. Those with a history of liver disease and excessive alcohol drinkers were excluded. The associations of serum six-carotenoid concentrations with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) stratified by glucose tolerance status were evaluated cross-sectionally. Serum AST and ALT concentrations in the groups of impaired fasting glucose (IFG) and diabetes were significantly higher than those in the normal group. The multivariate-adjusted means of the serum AST and ALT concentrations in IFG and diabetes group were significantly low in accordance with the tertiles of the serum beta-cryptoxanthin and beta-carotene concentrations. The most inverse association of serum liver enzyme and carotenoid concentration was observed in beta-cryptoxanthin. Antioxidant carotenoid, especially beta-cryptoxanthin, may act a deterrent substance against increasing the serum aminotransferase in the earlier pathogenesis of liver dysfunction among hyperglycemic subjects.
Diabetes Res Clin Pract 2006 Jan
PMID:Serum carotenoid concentrations are inversely associated with serum aminotransferases in hyperglycemic subjects. 1600 96

Alcoholic extract of the stems of Coscinium fenestratum, a medicinal plant indigenous to India and Sri Lanka used in ayurveda and siddha medicine for treating diabetes, was studied for its carbohydrate metabolism effect and antioxidant status in streptozotocin-nicotinamide induced type 2 diabetic rats. Oral administration of C. fenestratum stem extract in graded doses caused a significant increase in enzymatic antioxidants such as catalase, superoxide dismutase, glutathione synthetase, peroxidase, and glutathione peroxidase and in the nonenzymatic antioxidants ascorbic acid, ceruloplasmin and tocopherol. Effects of alcoholic extract on glycolytic enzymes such as glucose-6-phosphate dehydrogenase, lactate dehydrogenase and hexokinase showed a significant increase in their levels, whereas a significant decrease was observed in the levels of gluconeogenic enzyme, glucose-6-phosphatase and alanine aminotransferase in treated diabetic rats. Serum creatinine and urea levels also declined significantly. This investigation demonstrates significant antidiabetic activity of C. fenestratum.
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PMID:Alcoholic stem extract of Coscinium fenestratum regulates carbohydrate metabolism and improves antioxidant status in streptozotocin-nicotinamide induced diabetic rats. 1613 16

Nonalcoholic steatohepatitis is prevalent among obese individuals with excessive caloric intake, insulin resistance, and type II diabetes. However, no animal models exist that recapitulate this important association. This study produced and characterized steatohepatitis (SH) caused by intragastric overfeeding in mice. C57BL/6, tumor necrosis factor (TNF) type I receptor-deficient, and genetically matched wild type mice were fed via an implanted gastrostomy tube a high-fat diet for 9 weeks in the increasing amount up to 85% in excess of the standard intake. Animals were examined for weight gain, insulin sensitivity, and histology and biochemistry of liver and white adipose tissue (WAT). Overfed C57BL/6 mice progressively became obese, with 71% larger final body weights. They had increased visceral WAT, hyperglycemia, hyperinsulinemia, hyperleptinemia, glucose intolerance, and insulin resistance. Of these mice, 46% developed SH with increased plasma alanine aminotransferase (121 +/- 27 vs. 13 +/- 1 U/L), neutrophilic infiltration, and sinusoidal and pericellular fibrosis. Obese WAT showed increased TNFalpha and leptin expression and reciprocally reduced adiponectin expression. The expression of lipogenic transcription factors (SREBP-1c, PPARgamma, LXRalpha) was increased, whereas that of a lipolytic nuclear factor PPARalpha was reduced in SH. SH was associated with reduced cytochrome P450 (Cyp)2e1 but increased Cyp4a. TNF type I receptor deficiency did not prevent obesity and SH. In conclusion, forced overfeeding with a high-fat diet in mice induces obesity, insulin resistance, and SH in the absence of TNF signaling or Cyp2e1 induction.
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PMID:Steatohepatitis induced by intragastric overfeeding in mice. 1617 2

Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome, although it is not known whether markers of NAFLD, including elevated concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK), predict the development of metabolic syndrome. Our objective was to investigate the associations of elevated AST, ALT, and other liver markers, including C-reactive protein (CRP), with incident National Cholesterol Education Program-defined metabolic syndrome among 633 subjects in the Insulin Resistance Atherosclerosis Study who were free of metabolic syndrome at baseline. Insulin sensitivity (Si) and acute insulin response (AIR) were directly measured from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. After 5.2 years, 127 individuals had developed metabolic syndrome. In separate logistic regression models adjusting for age, sex, ethnicity, clinic, and alcohol consumption, subjects in the upper quartiles of ALT, ALK, and CRP were at significantly increased risk of incident metabolic syndrome compared with those in the lowest quartile: ALT, odds ratio 2.50 (95% CI 1.38-4.51); ALK, 2.28 (1.24-4.20); and CRP, 1.33 (1.09-1.63). Subjects in the upper quartile of the AST-to-ALT ratio were at significantly reduced metabolic syndrome risk (0.40 [0.22-0.74]). After further adjustment for waist circumference, Si, AIR, and impaired glucose tolerance, the associations of ALT and the AST-to-ALT ratio with incident metabolic syndrome remained significant (ALT, 2.12 [1.10-4.09]; the AST-to-ALT ratio, 0.48 [0.25-0.95]). These associations were not modified by ethnicity or sex, and they remained significant after exclusion of former and heavy drinkers. In conclusion, NAFLD markers ALT and the AST-to-ALT ratio predict metabolic syndrome independently of potential confounding variables, including directly measured Si and AIR.
Diabetes 2005 Nov
PMID:Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. 1624 37


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