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Published online April 11, 2007
Diabetes Care 30:1819-1827, 2007
DOI: 10.2337/dc07-0086
© 2007 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Article

Alanine Aminotransferase and Directly Measured Insulin Sensitivity in a Multiethnic Cohort

The Insulin Resistance Atherosclerosis Study

Anthony J.G. Hanley, PHD1,2, Lynne E. Wagenknecht, DRPH3, Andreas Festa, MD2, Ralph B. D'Agostino, Jr., PHD3 and Steven M. Haffner, MD2

1 Nutritional Sciences and Medicine and Leadership Sinai Centre for Diabetes, Mt. Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada
2 Clinical Epidemiology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas
3 Public Health Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina

Address correspondence and reprint requests to Dr. Steven Haffner, Clinical Epidemiology, University of Texas Health Science Center at San Antonio, Mail Code 7873, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: haffner{at}uthscsa.edu

OBJECTIVE— The objective of the present analysis was to evaluate the association of alanine aminotransferase (ALT) with directly measured insulin sensitivity (Si) in a large, multiethnic cohort of U.S. adults and to determine whether ALT adds to existing metabolic risk definitions in identifying subjects with insulin resistance.

RESEARCH DESIGN AND METHODS— Si was directly measured from frequently sampled intravenous glucose tolerance tests among 999 nondiabetic African-American, Hispanic, and non-Hispanic white subjects aged 40–69 years who were participating in the Insulin Resistance Atherosclerosis Study. Subjects also received an oral glucose tolerance test, and fasting insulin, ALT, and alcohol intake were determined.

RESULTS— ALT was associated with Si after adjustment for age, sex, ethnicity, impaired fasting glucose, triglycerides, HDL, blood pressure, and waist (clinical model) (P < 0.0001). The association remained significant after further adjustment for fasting insulin and impaired glucose tolerance (P = 0.004). In logistic regression analysis, elevated ALT (upper quartile) was associated with insulin resistance (lowest quartile of Si) after adjustment for age, sex, and ethnicity (odds ratio 3.0 [95% CI 2.2–4.1]). Elevated ALT was independently associated with insulin resistance when included in models with waist circumference, National Cholesterol Education Program criteria for metabolic syndrome, hypertriglyceridemic waist, elevated triglyceride-to-HDL ratio, or homeostasis model assessment of insulin resistance (HOMA-IR) (all P < 0.01). Finally, the addition of elevated ALT improved classification of insulin resistance by area under the receiver operating characteristic curve criteria for all models except HOMA-IR.

CONCLUSIONS— ALT was associated with insulin resistance independently of conventional and more detailed metabolic measures. These findings suggest that the addition of ALT to existing clinically based metabolic risk definitions is an inexpensive way to improve the identification of subjects with insulin resistance.

Abbreviations: ALK, alkaline phosphatase • ALT, alanine aminotransferase • AROC, area under the receiver-operating characteristic • AST, aspartate aminotransferase • CRP, C-reactive protein • CVD, cardiovascular disease • EWET, enlarged waist and elevated triglycerides • FSIVGTT, frequently sampled intravenous glucose tolerance test • GGT, {gamma}-glutamyl aminotransferase • HOMA-IR, homeostasis model assessment of insulin resistance • IFG, impaired fasting glucose • IGT, impaired glucose tolerance • IRAS, Insulin Resistance Atherosclerosis Study • NGT, normal glucose tolerance • NAFLD, nonalcoholic fatty liver disease • NCEP, National Cholesterol Education Program, Si, insulin sensitivity index


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