Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statins frequently do not control all of the lipid abnormalities found in patients with the metabolic sydrome. Pioglitizone (PIO), an insulin sensitizing agent, has been shown to have favorable lipid effects in diabetic patients. Little information is available regarding the effect of combined statin and PIO therapy in non-diabetic patients with the metabolic syndrome. We report our experience of adding PIO to statin therapy in non-diabetic patients with the metabolic syndrome. Pioglitazone was administered to 24 non-diabetic patients in our lipid clinic who were already on a statin yet continued to have significant lipid abnormalities. All patients had characteristic lipid abnormalities and clinical features of the metabolic syndrome. The treatment period was 59+/-29 (range 7-123) weeks. Lipid profiles, fasting glucose, and alanine aminotransferase were assessed before and at least 6 weeks after pioglitazone was added to statin. Triglyceride levels decreased from 307+/-295mg/dL to 173+/-129mg/dL (P=0.003), non-high-density lipoprotein cholesterol (non-HDL) decreased from 151+/-53mg/dL to 130+/-49mg/dL, (P=0.003), and high-density lipoprotein cholesterol (HDL) levels increased from 42+/-11mg/ dL to 45+/-12mg/dL, (P=0.039). The addition of PIO to statin in non-diabetic patients with metabolic sydrome produced significant additional benefits in the lipid profile over statin monotherapy. Favorable effects were seen in triglycerides, HDL, and non-HDL levels. Study limitations include: this is a small non-blinded observational study in which patients served as their own controls. The duration of combination therapy and type of statin employed were variable.
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PMID:Benefit of adding pioglitazone to statin therapy in non-diabetic patients with the metabolic syndrome. 1693 9

Increasing evidence suggests an association between elevated serum aminotransferase level and the metabolic syndrome. However, the significance of relatively low levels of aminotransferase in relation to the metabolic syndrome has not been fully investigated in the general population. We investigated the association between serum amiontransferase level and the metabolic syndrome using data from a nationwide survey in Korea. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and metabolic conditions among 9771 participants aged 20 or more in the 1998 and 2001 Korean National Health and Nutrition Examination Surveys. Metabolic syndrome was defined according to NCEP-ATP III criteria with a modified waist circumference cutoff (men > 90 cm; women > 80 cm). Serum aminotransferase level, even within normal range, was associated with the metabolic syndrome independent of age, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (< 20 IU/L), the adjusted odds ratios (95% CI) for an AST level of 20-29, 30-39, 40-49 and > or = 50 IU/L were 1.10 (0.85-1.42), 1.37 (1.02-1.83), 1.62 (1.08-2.43), and 2.25 (1.47-3.44) in men, and 1.18 (0.99-1.41), 1.43 (1.29-1.83), 1.71 (1.09-2.68), and 2.14 (1.20-3.80) in women, respectively. Corresponding odds ratios for ALT levels were 1.27 (0.99-1.63), 1.69 (1.28-2.23), 2.17 (1.58-2.99), and 2.65 (1.96-3.58) in men, and 1.44 (1.22-1.70), 1.65 (1.26-2.15), 2.94 (1.93-4.47), and 2.25 (1.54-3.30) in women, respectively. In conclusion, elevated serum aminotransferase levels, even in the normal to near normal range, are associated with features of the metabolic syndrome.
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PMID:Normal serum aminotransferase levels and the metabolic syndrome: Korean National Health and Nutrition Examination Surveys. 1694 45

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1-2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease.
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PMID:Who should receive a statin these days? Lessons from recent clinical trials. 1696 68

Cochlospermum vitifolium (Willd.) Sprengel is a Mexican medicinal plant that is used in the folk medicine for the treatment of hypertension, diabetes, hepatitis and related diseases. The purpose of the present study was to assess the pharmacological properties of different extracts from Cochlospermum vitifolium bark as potential agent for the treatment of some factors related with metabolic syndrome (MS), a complex disease produced for several pathophysiological factors such as visceral fat obesity, insulin resistance, hypertension, dyslipidemia and liver steatosis. Hexane (HECv), dichloromethane (DECv) and methanol (MECv) extracts were subjected to some pharmacological assays to determine their vasorelaxant and hypoglycemic activity. On the other hand, MECv was also evaluated to determine its hepatoprotective effect on sub-chronic experimental assay. HECv showed a significant endothelium-independent relaxation on rat aorta rings (intact endothelium: IC(50)=14.42+/-5.90 microg/mL, E(max)=92.71+/-8.9%; denuded endothelium: IC(50)=27.94+/-4.0 microg/mL, E(max)=78.68+/-4.6%) and MECv produced an endothelium-dependent relaxation (IC(50)=21.94+/-6.87 microg/mL, E(max)=79.12+/-7.80%) on this tissue. Furthermore, HECv (at a dose of 120 mg/kg) also showed a significant decrease of blood glucose levels (p<0.05) on normoglycemic rats. Moreover, MECv (at a dose of 100 mg/kg) also was administered to bile duct-obstructed rats to determine its hepatoprotective activity, showing a statistically significant decrease of serum glutamic-pyruvic transaminase (PGT, 45%) and alkaline phosphatase (APh, 15%) (p<0.05). Finally, we obtained a crystalline polyphenolic compound from MECv by spontaneous precipitation. Those crystals were identified as (+/-)-naringenin by X-ray diffraction, NMR, IR and GC-MS techniques. Results suggest that Cochlospermum vitifolium could be used as a potential agent against MS since it shows hypoglycemic, vasorelaxant and hepatoprotective properties.
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PMID:Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum vitifolium (Willd.) Sprengel: a potential agent for the treatment of metabolic syndrome. 1697 15

Nonalcoholic fatty liver disease (NAFLD) has been associated with metabolic disorders, including central obesity, dyslipidema, hypertension, and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of NAFLD. The aim of this study was to identify the relative contribution of the metabolic syndrome, obesity, and insulin resistance to alanine aminotransferase (ALT) activity in NAFLD. A total of 3091 subjects diagnosed with fatty liver by ultrasonography were enrolled. All components of metabolic syndrome criteria, anthropometric parameters, fasting insulin levels, high-sensitivity C-reactive protein (hs-CRP) as an inflammation marker, and ALT were measured in each subject. Homeostasis model assessment--insulin resistance (HOMA-IR) as a measure of insulin resistance and body mass index (BMI) as a measure of obesity were calculated. The prevalence of increased ALT levels (>40 IU/L) was 26.7%. Increased ALT activity was significantly associated with the following characteristics: male sex, young age, increased triglycerides, fasting glucose, fasting insulin, HOMA-IR, hs-CRP, waist circumference, BMI and diastolic blood pressure, and decreased high-density lipoprotein cholesterol (HDL-C). According to the increase in the number of metabolic syndrome components, BMI, HOMA-IR, and hs-CRP, the prevalence and odds ratio for having increased ALT activity were significantly increased. Central obesity, raised triglycerides, reduced HDL-C, and raised fasting glucose were strongly associated with increased ALT activity. In conclusion, a number of metabolic syndrome components, obesity, insulin resistance, and hs-CRP, are strong predictors of increased ALT activity in NAFLD. Central obesity, raised triglycerides, reduced HDL-C, and raised fasting glucose are metabolic syndrome components that contributed to increased ALT activity.
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PMID:The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease. 1714 31

We compared the levels of hepatic enzymes in 220 Japanese men with metabolic syndrome with those in age and sex-matched subjects without the syndrome. Metabolic syndrome was defi ned by the new criteria published in Japan, and hepatic enzymes, i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (gammaGTP), were measured. AST, ALT and gammaGTP in subjects with metabolic syndrome were significantly higher than those in subjects without the syndrome, and metabolic syndrome was closely associated with hepatic enzymes in this cohort of Japanese men.
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PMID:Comparison of hepatic enzymes between Japanese men with and without metabolic syndrome. 1733 39

There are limited data on nonalcoholic fatty liver disease (NAFLD) from India. The clinicopathological profile of Indian patients with NAFLD may be different from that of Western patients. One hundred NAFLD patients with increased liver enzymes were prospectively evaluated for clinical presentation, associated diseases, overweight/obesity, central obesity (n=54), presence of diabetes mellitus, lipid abnormalities, insulin resistance (n=39), metabolic syndrome (n=54), serum iron, serum ferritin, and transferrin saturation (n=60), and HFE gene mutations (n=30). Risk factors for the grade and stage of the disease on histology were studied in 38 biopsy-proven patients. Patients were treated with lifestyle modifications and ursodeoxycholic acid (UDCA). Seventeen nonresponder patients were treated with metformin. The majority of patients were males (n=70). Twenty percent of patients were overweight, 68% had obesity, and 78% had central obesity. Abnormal cholesterol, HDL, and triglycerides were present in 36%, 66%, and 53% of patients, respectively. Twelve percent of patients had diabetes mellitus and 16% patients had various associated diseases. All 22 (100%) patients studied by ITT and all but 1 (98%) studied by HOMA-IR were found to have reduced insulin sensitivity and 50% were found to have metabolic syndrome by the modified ATP III criteria. Two (3%) patients were found to have high serum iron, 4 (7%) patients had high ferritin, 5 (8%) patients had increased transferrin saturation, and 4 (13%) patients were found to be heterozygotes for H63D HFE gene mutation. Twenty patients of 38 (53%) had histological evidence of NASH (class 3=6, class 4=14). The other 18 (47%) qualified for class I (n=1) or class II (n=17) NAFLD. Four (10.5%) patients had bridging fibrosis and none had evidence of cirrhosis liver. Seventy-four (74%) patients achieved a biochemical response to lifestyle modification and UDCA. All 17 patients treated with metformin had a reduction in ALT level and 10 (59%) of them had normalization of their enzymes. We conclude that the clinicopathological profile of NAFLD in Indian patients is different from that in the West.
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PMID:The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. 1742 Sep 51

Elevations in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of the metabolic syndrome and related diseases. However, information is limited regarding the persistence (tracking) in levels of these enzymes over time and their influence on cardiovascular (CV) risk in young adults. The study sample consisted of white and black subjects (N = 489, 40% male, 73% white; baseline age, 18-32 years) followed over a period of 12 years as part of the Bogalusa Heart Study, with repeat measurements of CV risk factor variables and liver enzymes. Both at baseline and follow-up, males vs females had higher ALT (P < .01 to .0001) and GGT (P < .0001); blacks vs whites had higher GGT (P < .0001). With respect to persistence in enzyme levels over time, of those individuals who had ALT and GGT at the top quintile specific for age, race, and sex at baseline, about 50% of them continued to remain so with high values after 12 years. Individuals with levels persistently in the highest quintile vs those in the lowest quintile showed higher (P < .0001) body mass index, waist circumference, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, insulin resistance index, and systolic and diastolic blood pressures; lower (P < .0001) high-density lipoprotein cholesterol; and higher (P < .05 to .001) prevalence of obesity, hypertension, dyslipidemia, metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III, positive parental history of type 2 diabetes, and coronary heart disease. In addition, based on a multivariate analysis using 2 separate models for ALT and GGT, baseline levels of both enzymes were independent predictors of follow-up; insulin resistance index and baseline GGT were also predictive of follow-up systolic blood pressure. Elevations in liver enzymes ALT and GGT, within "reference" range, persist over time and relate to clinically relevant adverse CV risk profile in young adults.
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PMID:Persistent elevation of liver function enzymes within the reference range is associated with increased cardiovascular risk in young adults: the Bogalusa Heart Study. 1751 12

This study investigated the effects of rimonabant (SR141716), an antagonist of the cannabinoid receptor type 1 (CB1), on obesity-associated hepatic steatosis and related features of metabolic syndrome: inflammation (elevated plasma levels of tumor necrosis factor alpha [TNFalpha]), dyslipidemia, and reduced plasma levels of adiponectin. We report that oral treatment of obese (fa/fa) rats with rimonabant (30 mg/kg) daily for 8 weeks abolished hepatic steatosis. This treatment reduced hepatomegaly, reduced elevation of plasma levels of enzyme markers of hepatic damage (alanine aminotransferase, gamma glutamyltransferase, and alkaline phosphatase) and decreased the high level of local hepatic TNFalpha currently associated with steatohepatitis. In parallel, treatment of obese (fa/fa) rats with rimonabant reduced the high plasma level of the proinflammatory cytokine TNFalpha and increased the reduced plasma level of the anti-inflammatory hormone adiponectin. Finally, rimonabant treatment also improved dyslipidemia by both decreasing plasma levels of triglycerides, free fatty acids, and total cholesterol and increasing the HDLc/LDLc ratio. All the effects of rimonabant found in this study were not or only slightly observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with rimonabant compared to diet. These results demonstrate that rimonabant plays a hepatoprotective role and suggest that this CB1 receptor antagonist potentially has clinical applications in the treatment of obesity-associated liver diseases and related features of metabolic syndrome.
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PMID:Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. 1759 67

Evidence-based management guidelines for non-alcoholic fatty liver disease (NAFLD) are lacking in the Asia-Pacific region or elsewhere. This review reports the results of a systematic literature search and expert opinions. The Asia-Pacific Working Party on NAFLD (APWP-NAFLD) has generated practical recommendations on management of NAFLD in this region. NAFLD should be suspected when there are metabolic risk factors and/or characteristic changes on hepatic ultrasonography. Diagnosis by ultrasonography, assessment of liver function and complications, exclusion of other liver diseases and screening for metabolic syndrome comprise initial assessment. Liver biopsy should be considered when there is diagnostic uncertainty, for patients at risk of advanced fibrosis, for those enrolled in clinical trials and at laparoscopy for another purpose. Lifestyle measures such as dietary restrictions and increased physical activity (aerobic exercise) should be encouraged, although the best management strategy to achieve this has yet to be defined. Complications of metabolic syndrome should be screened for regularly. Use of statins to treat hypercholesterolemia is safe and recommended; frequent alanine aminotransferase (ALT) monitoring is not required. Obese patients who do not respond to lifestyle measures should be referred to centers specializing in obesity management; consideration should be given to bariatric surgery or gastric ballooning. The role of pharmacotherapy remains investigational and is not recommended for routine clinical practice. Non-alcoholic fatty liver disease should be recognized as part of the metabolic syndrome and managed in a multidisciplinary approach that addresses liver disease in the context of risk factors for diabetes and premature cardiovascular disease. Lifestyle changes are the first line and mainstay of management.
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PMID:How should we manage patients with non-alcoholic fatty liver disease in 2007? 1756 32


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