Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the absence of existing research, we examined the association between longitudinal changes in serum gamma-glutamyltransferase (GGT) levels and the risk for metabolic syndrome (MetS). A MetS-free cohort of 9148 healthy male workers, who had participated in a health checkup program in 2002, was followed until September 2007. Metabolic syndrome was defined according to the modified National Cholesterol Education Program, using body mass index instead of waist circumference. Standard Cox proportional hazards and time-dependent Cox models were performed. During 37 663.4 person-years of follow-up, 1056 men developed MetS. The risk of incident MetS increased across the baseline GGT quartiles, even after further updating GGT values during the follow-up. A longitudinal increase in GGT as a time-dependent variable as well as a non-time-dependent variable was significantly related to MetS after adjusting for age plus the elapsed time from visit 1 to visit 2, baseline MetS traits, uric acid, regular exercise, alcohol consumption, and smoking. Even within the GGT reference interval (<40 U/L), the fourth quartile of GGT change predicted the development of MetS (adjusted hazard risk, 1.61; 95% confidence interval, 1.26-2.07). Furthermore, these associations were consistently observed within the subgroups-those with body mass index less than 23 kg/m(2), C-reactive protein less than 3.0 mg/L, homeostasis model assessment of insulin resistance less than 2.04, alcohol intake not exceeding 20 g/d, alanine aminotransferase less than 35 U/L, an absence of ultrasonographically detected fatty liver, and an absence of any MetS traits. A longitudinal increase in the GGT level, even within the GGT reference interval, may be an independent predictor for MetS, regardless of the baseline GGT.
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PMID:Longitudinal increase in gamma-glutamyltransferase within the reference interval predicts metabolic syndrome in middle-aged Korean men. 1992 66

The aim of this study was to determine whether a relatively low dose of pioglitazone or metformin was effective in diabetic patients with metabolic syndrome. Fifty diabetic patients with metabolic syndrome were randomly assigned to a low-dose pioglitazone (15 mg/day) treatment group or a low-dose metformin (500 mg/day) treatment group. Drugs were administered for 12 weeks. Systolic and diastolic blood pressure, heart rate, body mass index, triglyceride (TG), HDL and LDL-cholesterol, fasting plasma glucose (FPG), fasting plasma insulin (IRI), postprandial glucose, and HOMA-IR in the 75gOGTT, HbA1c, high-sensitivity CRP (hs-CRP) determined by cervical artery echography, and pulse wave velocity (PWV) were measured before/after 12-week drug administration. Significant decreases in HbA1c and HOMA-IR were noted in the pioglitazone group, along with significant decreases in TG, AST, ALT, blood pressure, hs-CRP and PWV. Significant decreases in HbA1c, HOMA-IR, BMI and waist circumference were noted in the metformin group. The pioglitazone group significantly improved the values for ALT, systolic blood pressure, hs-CRP and PWV compared to the metformin group. However, the metformin group demonstrated significant improvement in BMI compared with the pioglitazone group. Using a low dose regimen, pioglitazone significantly improved blood pressure and hepatic function and may be more effective than metformin to reduce risk factors in Japanese diabetic patients with metabolic syndrome at preventing atherosclerosis.
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PMID:Comparative study of low-dose pioglitazone or metformin treatment in Japanese diabetic patients with metabolic syndrome. 1992 5

Mean platelet volume (MPV) is an indicator of platelet activation. Platelet activation and aggregation are central processes in the pathophysiology of coronary heart disease. Non-alcoholic fatty liver disease (NAFLD) is present up to one-third of the general population and the majority of patients with cardio-metabolic risk factors such as abdominal obesity, type 2 diabetes and other components of the metabolic syndrome (MS). The aim of the current study was to investigate the MPV in patients who had NAFLD. MPV values of the patients with NAFLD and of the patients without fatty liver disease were compared. NAFLD patients had significantly higher body mass index compared to the control cases. Among biochemical variables, fasting plasma glucose and triglyceride were significantly higher in the NAFLD group. NAFLD cases also had lower platelet count and higher MPV (10.43 +/- 1.14 vs. 9.09 +/- 1.25; p < 0.001, respectively). MPV was positively correlated with AST (r: 0.186, p < 0.042), ALT level (r: 0.279; p 0.002) and the presence of NAFLD (0.492; p < 0.001) but negatively correlated with platelet number (r: -0.26; p 0.004) and creatinine (r: -0.255; p 0.005). In logistic regression analysis (age, gender, NAFLD, body mass index, high-density lipid (HDL) cholesterol, systolic and diastolic blood pressure, triglyceride and fasting plasma glucose were used as covariates) only NAFLD was found to be the independent predictor of MPV (Odds Ratio (OR) 21.98) [95% confidence interval (CI): 2.404-201.048; p: 0.006]. We have shown for the first time in the literature that, patients with NAFLD have higher MPV. It may have prognostic value in NAFLD patients indicating a possible cardiovascular disease (CVD) risk increase.
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PMID:Mean platelet volume in patients with non-alcoholic fatty liver disease. 2114 6

Cardiovascular disease (CVD) is a leading cause of mortality in renal transplant recipients (RTRs). Metabolic syndrome (MS) is highly prevalent in RTRs. Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of MS. We investigated associations of NAFLD markers with MS and mortality. RTRs were investigated between 2001 and 2003. NAFLD markers, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were measured. Bone and nonbone fractions of AP were also determined. Death was recorded until August 2007. Six hundred and two RTRs were studied (age 52+/-12 years, 55% men). At baseline 388 RTRs had MS. Prevalence of MS was positively associated with liver enzymes. During follow-up for 5.3[4.5-5.7] years, 95 recipients died (49 cardiovascular). In univariate Cox regression analyses, GGT (HR=1.43[1.21-1.69], p<0.001) and AP (HR=1.34[1.11-1.63], p=0.003) were associated with mortality, whereas ALT was not. Similar associations were found for cardiovascular mortality. Adjustment for potential confounders, including MS, diabetes and traditional risk factors did not materially change these associations. Results for nonbone AP mirrored that for total AP. ALT, GGT and AP are associated with MS. Of these three enzymes, GGT and AP are associated with mortality, independent of MS. These findings suggest that GGT and AP are independently related to mortality in RTRs.
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PMID:Markers of the hepatic component of the metabolic syndrome as predictors of mortality in renal transplant recipients. 1995 Dec 80

Insulin resistance, obesity, hypertension, and dyslipidemia are strongly associated with metabolic syndrome (MeSy), which is considered to be a reversible clinical stage before its evolution to coronary heart disease and diabetes. Currently, the antihypertensive and hypolipidemic properties of aqueous Hibiscus sabdariffa extracts (HSE) have been demonstrated in clinical trials and in vivo experiments. The aim of the present study was to evaluate the effects of a Hibiscus sabdariffa extract powder (HSEP) and a recognized preventive treatment (diet) on the lipid profiles of individuals with and without MeSy according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The protocol was a follow-up study carried out in a factorial, randomized design (T1=preventive treatment comprises Diet, T2=HSEP, T3=HSEP+preventive treatment (Diet) X MeSy, non-MeSy individuals). A total daily dose of 100 mg HSEP was orally administered in capsules for one month. The preventive treatment (diet) was selected according to NCEP-ATP III recommendations and adjusted individually. Total cholesterol, LDL-c, HDL-c, VLDL-c, triglycerides, glucose, urea, creatinine, AST, and ALT levels in the blood were determined in all individuals pre- and post-treatment. The MeSy patients treated with HSEP had significantly reduced glucose and total cholesterol levels, increased HDL-c levels, and an improved TAG/HDL-c ratio, a marker of insulin resistance (t-test p<0.05). Additionally, a triglyceride-lowering effect was observed in MeSy patients treated with HSEP plus diet, and in individuals without MeSy treated with HSEP. Significant differences in total cholesterol, HDL-c, and the TAG/HDL-c ratio were found when the means of absolute differences among treatments were compared (ANOVA p<0.02). Therefore, in addition to the well documented hypotensive effects of Hibiscus sabdariffa, we suggest the use of HSEP in individuals with dyslipidemia associated with MeSy.
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PMID:Effects of Hibiscus sabdariffa extract powder and preventive treatment (diet) on the lipid profiles of patients with metabolic syndrome (MeSy). 1996 89

Recently, obesity (BMI>or=25 kg/m2) and type II diabetes mellitus have reached epidemic proportions in Korea, and rates of nonalcoholic fatty liver disease (NAFLD) are between 10% and 25% of the general population. NAFLD in Korea is as closely associated with several components of metabolic syndrome including, obesity, hypertension, diabetes and dyslipidemia as it is in Western countries. Insulin resistance and hyperinsulinemia may play a role in the pathogenesis of fatty liver in patients with normal body weight as well as in patients with obesity. And, obesity induced accumulation of fat in the adipose tissue leads to an imbalance in the regulation of adipokines, such as downregulation of adiponectin and upregulation of retinol-binding protein 4 (RBP4) and ghrelin. High BMI, the AST/ALT ratio, and ALT levels could be used to distinguish NASH from simple steatosis in Korean patients. In large number of NAFLD patients who underwent a voluntary medical checkup, even a small weight reduction was associated with improvements in their hepatic steatosis grade on ultrasonography, serum aminotransferase levels, and related metabolic abnormalities. Subjects with fatty liver disease should be advised to lose weight through lifestyle modifications. Small animal and human studies of treatment with PPAR agonists and betaine have been reported in the Korean literature. It is now acknowledged that NAFLD is the most common liver disease in Korea, largely due to the considerable increase in metabolic abnormalities such as obesity and diabetes. Future studies should continue to focus both on the pathogenesis and the treatment of NAFLD in order to accumulate more of our own data.
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PMID:Current status of liver disease in Korea: nonalcoholic fatty liver disease. 2003 78

Elevated serum amino-transferase levels may be associated with liver injury. Testing for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is part of many routine screening approaches. The aim of this manuscript was to scrutinize the evidence for using ALT testing as a primary screening parameter for liver diseases. We conclude that (i) elevated serum ALT levels indicate a high specificity and a reasonable sensitivity liver injury, (ii) 10 - 25 % of German adults have elevated ALT levels, (iii) ALT values are increased in the majority but not all patients with acute and chronic liver disease (iv) elevated ALT-values are associated with an increased risk of liver-specific mortality, (v) elevated ALT values are also a risk factor for non-hepatic diseases including diabetes mellitus type 2, metabolic syndrome, cardiovascular diseases and malignancies, (vi) many liver diseases identified by an ALT screening can be treated successfully including prevention of development of clinical endpoints, (vii) an ALT-screening is very likely to be cost-effective although studies are needed for Germany to support this conclusion.
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PMID:[ALT screening for chronic liver diseases: scrutinizing the evidence]. 2007 96

Since the widespread introduction of the blood test requirement for life insurance, the interpretation of liver function tests (AST, ALT, GGT) has generated intense interest. Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been shown to be associated with primary liver diseases, as well as increased all-cause mortality. Much of this mortality is mediated by increased cardiovascular risk. Gamma-glutmyltransferase (GGT) has been shown to be a marker for metabolic syndrome and diabetes, cardiovascular diseases and mortality, chronic kidney disease, as well as cancer incidence, and liver disease. In this paper we present a mortality study of abnormal liver function test (LFT) results using a direct life insurer's underwriting application data covering approximately 560,000 applications with insurance blood profiles. The results show a consistent progression of increasing risk ratios as the severity of the LFT finding increases. When GGT alone is elevated or when both ALT and AST are elevated, mortality risk is significantly elevated. Similarly, a trend toward higher mortality with progressively higher levels of ALT, AST and GGT is demonstrated. Related liver chemistry results (alkaline phosphatase, bilirubin, albumin), other risk factors, and age are also considered.
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PMID:Liver function tests and mortality in a cohort of life insurance applicants. 2037 96

Obesity is a heterogeneous disorder with metabolically healthy and unhealthy phenotypes and varying degrees of cardiometabolic complications. To evaluate whether alanine aminotransferase (ALT) could be used for identification of obese phenotypes, the authors measured ALT, adiponectin, leptin, leptin receptor, free leptin index, high-sensitivity C-reactive protein, fasting insulin, glucose, and full lipid profile in 486 (176 men and 310 women) normoglycemic first-degree relatives of patients with type 2 diabetes mellitus with negative medication history and hepatitis screen. Patients were classified into obesity phenotypes on the basis of the degree of adiposity and the International Diabetes Federation criteria for the metabolic syndrome. One hundred and thirty-seven (28%) patients were positive for the metabolic syndrome, 32 (7%) had normal weight but metabolically unhealthy phenotype, and 201 (41%) were obese but metabolically healthy. ALT showed significant positive correlations with body mass index, waist circumference, beta-cell function, insulin, homeostasis model assessment for insulin resistance, high-sensitivity C-reactive protein, total cholesterol, and triglycerides and increased with increasing number of metabolic syndrome components. Binary logistic regression analyses showed that higher ALT levels within the normal range were significantly associated with the metabolic syndrome. ALT could be used for identification of the metabolically obese phenotype. Lowering the ALT upper normal reference limit will facilitate earlier detection of risky phenotypes of obesity.
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PMID:Higher levels of alanine aminotransferase within the reference range predict unhealthy metabolic phenotypes of obesity in normoglycemic first-degree relatives of patients with type 2 diabetes mellitus. 2043 54

Abstract Alcohol abuse is a major cause of abnormal liver function throughout the world. While measurements of liver enzyme activities (GGT, ALT, AST) are important screening tools for detecting liver disease, due to lack of ethanol-specificity and inconsistencies regarding the definitions of significant alcohol consumption, several other blood tests are usually needed to exclude competing and co-existing causes of abnormal liver function. Information on the specific role of ethanol consumption behind hepatotoxicity may be obtained through measurements of blood ethanol and its specific metabolites (ethyl glucuronide, phosphatidylethanol, protein-acetaldehyde condensates and associated autoimmune responses). Recent studies have indicated that being overweight is another increasingly common cause of abnormal liver enzyme levels and adiposity may also increase the impact of ethanol consumption on liver pathology. Interestingly, increased liver enzyme activities in circulation may reflect not only hepatic function but can also serve as indicators of general health and the status of oxidative stress in vivo. ALT and GGT activities predict insulin resistance, metabolic syndrome, mortality from coronary heart diseases and even mortality from all causes. If the upper reference limits for liver enzyme activities were defined based on the data obtained from normal weight abstainers, the clinical value of liver enzyme measurements as screening tools and in patient follow-up could be significantly improved.
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PMID:Biomarkers of alcohol consumption and related liver disease. 2047 Feb 13


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