Dataset Information

Synergistic association between alcohol intake and body mass index with serum alanine and aspartate aminotransferase levels in older adults: the Rancho Bernardo Study.

ABSTRACT: The association between body-mass-index (BMI), alcohol consumption and their joint effect in increasing the risk of elevated serum alanine (ALT) and aspartate (AST) is unclear in older community-dwelling adults.To determine the association between alcohol, BMI, and their combined effect with serum ALT and AST in older community-dwelling adults in the United States.A cross-sectional, population-based study in participants (n = 2364) from the Rancho Bernardo Study (54% women; mean age: 70 years, BMI: 25 kg/m(2), alcohol users: 63%) who attended a research visit in 1984-87. BMI was recorded by a trained nurse and alcohol use ascertained by a validated questionnaire. Odds-ratio (OR) and 95% confidence intervals (CI) of elevated serum ALT and AST (defined as > or =30 U/L in men and > or =19 U/L in women) were calculated for alcohol and BMI separately and their joint exposure using logistic regression models.In multivariate logistic regression models adjusted for age, alcohol use, total cholesterol, serum triglycerides, fasting plasma glucose, systolic blood pressure, and diabetes mellitus, obesity independently increased the odds of elevated ALT in this cohort of older men and women by 3.0 (95% CI, 1.7-5.3) and 1.8 (95% CI, 1.1-2.7) respectively. Joint effects of consuming >3 alcoholic drinks/day and obesity raised the odds of elevated ALT by 8.9 (95% CI, 2.4-33.1) and AST by 21-fold (95% CI, 2.6-170.1), demonstrating synergism. Obese participants had higher odds of elevated ALT even at 0 < or = 1 drink/day.In older men and women, the combination of obesity with alcohol is synergistic in increasing the risk of liver injury.

SUBMITTER: Loomba R

PROVIDER: S-EPMC3220929 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Synergistic association between alcohol intake and body mass index with serum alanine and aspartate aminotransferase levels in older adults: the Rancho Bernardo Study.

Loomba R R Bettencourt R R Barrett-Connor E E

Alimentary pharmacology & therapeutics 20090908 11-12

<h4>Background</h4>The association between body-mass-index (BMI), alcohol consumption and their joint effect in increasing the risk of elevated serum alanine (ALT) and aspartate (AST) is unclear in older community-dwelling adults.<h4>Aim</h4>To determine the association between alcohol, BMI, and their combined effect with serum ALT and AST in older community-dwelling adults in the United States.<h4>Methods</h4>A cross-sectional, population-based study in participants (n = 2364) from the Rancho B ...[more]

PMID: 19737152

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Project description:Experiments were conducted with intact rat hepatocytes to identify inhibitors and incubation conditions that cause selective inhibition of alanine aminotransferase or aspartate aminotransferase. Satisfactory results were obtained by preincubating cells with L-cycloserine or L-2-amino-4-methoxy-trans-but-3-enoic acid in the absence of added substrates. When cells were incubated for 20 min with 50 microM-L-cycloserine, alanine aminotransferase activity was decreased by 90%, whereas aspartate aminotransferase was inhibited by 10% or less. On subsequent incubation, synthesis of glucose and urea from alanine was strongly inhibited, but glucose synthesis from lactate was unaffected. L-2-Amino-4-methoxy-trans-but-3-enoic acid (400 microM) in hepatocyte incubations caused 90-95% inactivation of aspartate aminotransferase, but only 15-30% loss of alanine aminotransferase activity. After preincubation with the inhibitor, glucose synthesis from lactate was almost completely blocked; with alanine as the substrate, gluconeogenesis was unaffected, and urea synthesis was only slightly decreased. By comparison with preincubation with inhibitors, simultaneous addition of substrates (alanine; lactate plus lysine) and inhibitors (cycloserine; aminomethoxybutenoic acid) resulted in smaller decreases in aminotransferase activities and in metabolic rates. Other compounds were less satisfactory as selective inhibitors. Ethylhydrazinoacetate inactivated the two aminotransferases to similar extents. Vinylglycine was almost equally effective in blocking the two enzymes in vitro, but was a very weak inhibitor when used with intact cells. Concentrations of DL-propargylglycine (4 mM) required to cause at least 90% inhibition of alanine aminotransferase in hepatocytes also caused a 16% decrease in aspartate aminotransferase. When tested in vitro, alanine aminotransferase was, as previously reported by others, more sensitive to inhibition by amino-oxyacetate than was aspartate aminotransferase, but in liver cell incubations the latter enzyme was more rapidly inactivated by amino-oxyacetate.

Project description:The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.

Dataset Information

Synergistic association between alcohol intake and body mass index with serum alanine and aspartate aminotransferase levels in older adults: the Rancho Bernardo Study.

Publications

Synergistic association between alcohol intake and body mass index with serum alanine and aspartate aminotransferase levels in older adults: the Rancho Bernardo Study.

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