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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. lorenzo@uthscsa.edu
C
C
Lorenzo
A J
AJ
Hanley
M J
MJ
Rewers
S M
SM
Haffner
D050154:Adiposity; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D001053:Apolipoproteins / Q000097:blood*; D050197:Atherosclerosis / Q000097:blood* / Q000208:ethnology / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
D001053:Apolipoproteins; D008074:Lipoproteins; D000410:Alanine Transaminase