Background & aims: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of obesity and metabolic syndrome (MetS). Alanine aminotransferase (ALT) levels are used to detect NAFLD and have also been associated with increased risk for MetS, diabetes mellitus, and cardiovascular disease (CVD). We studied the relationship between ALT levels and these disorders in a long-term follow-up study.

Methods: Framingham Offspring Heart Study participants (n = 2812; mean age, 44 years; 56% women) were followed for the development of MetS, diabetes, CVD, and all-cause mortality using logistic regression (MetS, diabetes) or Cox proportional hazards models (CVD, all-cause mortality).

Results: Among individuals at baseline, per 1 standard deviation increase in log ALT level, there were increased odds of the development of MetS (odds ratio [OR] 1.21, P < .001) and diabetes (OR, 1.48; P < .0001) over 20 years of follow-up. These findings also applied to participants with ALT levels within the normal range (MetS OR, 1.17; P = .006; diabetes OR, 1.34; P =.002). There was an increased risk of CVD in age/gender-adjusted models (hazard ratio, 1.23; P < .0001), but this was attenuated in multivariable-adjusted models (hazard ratio 1.05; P = .27); no association was observed for all-cause mortality. Aspartate aminotransferase levels were found to be associated with an increased risk of only diabetes.

Conclusions: Both normal and increased levels of ALT are associated with long-term development of multiple metabolic disorders. These results indicate the potential for ALT values as biomarkers for the risk of metabolic disease.