Aminotransferase levels as a potential biomarker for the risk of metabolic disease
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Alanine aminotransferase (ALT) is a liver-specific cytosolic enzyme, the circulating levels of which are used for non-invasive screening of nonalcoholic fatty liver disease (NAFLD). ALT levels have also been associated with increased risk of metabolic disease, type 2 diabetes mellitus, and cardiovascular disease (CVD). In order to investigate the relationship between ALT levels and metabolic disorders, 2812 participants of the Framingham Offspring Heart Study were followed-up over 20 years. The primary outcomes were incident metabolic syndrome and its components, diabetes, CVD, and all-cause mortality. Logistic regression analysis or Cox proportional hazards models revealed that, per 1 standard deviation increase in log(ALT) level at baseline, there were increased odds of developing a metabolic syndrome and diabetes during follow-up, these findings being also applicable to subjects presenting with ALT levels within the normal range. In age/gender-adjusted models, there was an increased risk of CVD, which was attenuated in multivariable-adjusted models. No association was observed for all-cause mortality. A significant interaction was found between obesity, ALT levels, and incident diabetes, suggesting that for the latter, the combination of both former conditions was more detrimental than either alone. These results indicate the potential for ALT values as a biomarker for incident risk of metabolic disease, including diabetes.
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