The association of alanine aminotransferase within the normal and mildly elevated range with lipoproteins and apolipoproteins: The Insulin Resistance Atherosclerosis Study

Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA, .
Diabetologia (Impact Factor: 6.67). 01/2013; 56(4). DOI: 10.1007/s00125-012-2826-4
Source: PubMed


Markers of liver injury, such as alanine aminotransferase (ALT), have been associated with atherogenic lipoprotein changes. We examined the extent to which this association was explained by insulin resistance, adiposity, glucose tolerance and chronic inflammation.

In this analysis we included 824 non-diabetic participants (age 40-69 years) in the Insulin Resistance Atherosclerosis Study. No participants reported excessive alcohol intake or treatment with lipid-lowering medications. Lipoproteins and apolipoproteins were measured by conventional methods and lipoprotein heterogeneity by nuclear magnetic resonance (NMR) spectroscopy.

ALT had a positive relationship with triacylglycerols, LDL-to-HDL-cholesterol ratio and apolipoprotein B (ApoB) after adjusting for demographic variables (p < 0.001 for all three relationships). ALT was also associated with the following NMR lipoproteins: positively with large VLDL (p < 0.001), intermediate-density lipoprotein (IDL) (p < 0.001) and small LDL subclass particles (p < 0.001), and VLDL particle size (p < 0.001); and negatively with large LDL subclass particles (p < 0.05) and LDL (p < 0.001) and HDL particle sizes (p < 0.01). ALT remained associated with IDL and small LDL subclass particles and ApoB after adjusting for glucose tolerance, adiposity, directly measured insulin sensitivity and C-reactive protein.

ALT is associated with a wide range of atherogenic lipoprotein changes, which are partially explained by insulin resistance, adiposity, glucose tolerance and chronic inflammation. Because of the significant variability in the relationship between ALT and liver fat, further studies are needed to assess the extent of the lipoprotein changes using a direct measure of liver fat.

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    • "All of the enrolled participants were selected within the ULN values (the ULN value is 30 U/l for males and 19 U/l for females) 80. Another Korean national health survey also showed a significantly increased prevalence of MetS components, as defined by NCEP-ATP-III criteria, in the subgroup with high-normal ALT levels 81. With respect to the lipoproteins, ALT was shown to be stably and significantly associated with intermediate-density lipoprotein (IDL) and apolipoprotein B (ApoB) after adjusting various covariates in different models 82. These associations were commonly attributed to the stable and independent effects of insulin resistance and fatty liver disease in subjects with ALT elevations 6, 49. "
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