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Comparative Study
. 2008 Dec;135(6):1935-44, 1944.e1.
doi: 10.1053/j.gastro.2008.09.018. Epub 2008 Sep 20.

Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease

Wolfram Goessling  1 , Joseph M Massaro, Ramachandran S Vasan, Ralph B D'Agostino Sr, R Curtis Ellison, Caroline S Fox
Affiliations
Comparative Study

Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease

Wolfram Goessling et al. Gastroenterology. 2008 Dec.

Abstract

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.

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Figures

Figure 1
Figure 1
1) Figure 1a.– Age-sex adjusted odds ratios of diabetes by sex-specific tertiles of ALT (tertile 1, light grey bars; tertile 2, medium grey bars, tertile 3, dark grey bars) and by clinical BMI categories (normal weight [BMI <25], overweight [BMI 25–29.9], obese [BMI 30+]) over 20-years of follow-up. Ranges for ALT tertiles were as follows (U/L): men: 1–21; 22–32; 33–104; women: 2–15; 16–22; 23–118. 2) Figure 1b. - Age-sex adjusted odds ratio of MetS by sex-specific tertiles of ALT and by clinical BMI categories (normal weight [BMI <25], overweight [BMI 25–29.9], obese [BMI 30+]) over 20-years of follow-up. Ranges for ALT tertiles were as follows (U/L): men: 1–21; 22–32; 33–104; women: 2–15; 16–22; 23–118.
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