Gastroenterology

Gastroenterology

Volume 135, Issue 6, December 2008, Pages 1935-1944.e1
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
Aminotransferase Levels and 20-Year Risk of Metabolic Syndrome, Diabetes, and Cardiovascular Disease

https://doi.org/10.1053/j.gastro.2008.09.018Get rights and content

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.

Section snippets

Study Sample

The Framingham Heart Study began in 1948;27, 28 in 1971, 5,124 men and women were enrolled into the Framingham Offspring Study, which included the children or spouses of the children of the original cohort. Offspring subjects underwent examinations approximately every 4 years, as previously described.29 The current investigation is composed of subjects from the Framingham Offspring Study who attended a baseline examination in 1978–1982 (second examination cycle), when aminotransferase levels

Baseline Characteristics

The baseline characteristics of the study participants are summarized in Table 1. The mean age of the participants at baseline was 44 years, and 56% were women. The baseline prevalence of obesity was 14.2%, of MetS 20.1%, and of CVD 4.0%. The age/gender-adjusted correlation between log ALT and log AST was 0.54 (P < .001).

Incident MetS and its Components

Among individuals free of MetS and diabetes at baseline, 621 developed MetS at 20-year follow-up (Table 2). The results for individuals in the overall sample are shown in Table

Discussion

The most important finding in our study is the association between ALT levels and the development of incident MetS and DM over 20 years of follow-up. These results were observed when analyzed in the overall cohort, including individuals with elevated ALT levels to 3 times the upper limit of normal. The results remained significant, however, for individuals with ALT values within the normal range. A significant interaction was observed between obesity status, ALT levels, and the development of

Conclusions

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 for metabolic disease.

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    The authors disclose the following: Supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195). W.G. is supported by K08-DK071940 (NIDDK/NIH). R.S.V. is supported in part by 2K24HL04334 (NHLBI/NIH). W.G. and C.S.F. designed and conducted the study, analyzed and interpreted the data, and prepared the manuscript. They had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. J.M.M. performed all the statistical analyses. All authors reviewed and approved the manuscript.

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