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Alanine Aminotransferase (ALT) and Directly Measured Insulin Sensitivity in a Multi-ethnic Cohort The Insulin Resistance Atherosclerosis Study

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

haffner{at}uthscsa.edu

ABSTRACT

Objective: The objective of the present analysis was to evaluate the association of ALT with directly-measured insulin sensitivity (S_I) in a large, multi-ethnic cohort of US adults, and to determine whether ALT adds to existing metabolic risk definitions in identifying subjects with IR.

Research Design and Methods: S_I was directly measured from frequently sampled intravenous glucose tolerance tests among 999 non-diabetic African American, Hispanic and non-Hispanic white subjects aged 40-69 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 S_I after adjustment for age, sex, ethnicity, impaired fasting glucose, triglyceride, HDL, blood pressure and waist (clinical model) (p<0.0001). The association remained significant after further adjustment for fasting insulin and impaired glucose tolerance (IGT) (p=0.004). In logistic regression analysis, elevated ALT (upper quartile) was associated with IR (lowest quartile of S_I) after adjustment for age, gender, and ethnicity (OR = 3.0, 95% CI 2.2-4.1). Elevated ALT was independently associated with IR when included in models with waist, NCEP metabolic syndrome (MetS), hypertriglyceridemic waist, elevated Tg/HDL, or HOMA IR (all p<0.01). Finally, the addition of elevated ALT improved classification of insulin resistance by AROC curve criteria for all models except HOMA IR.

Conclusions: ALT was associated with IR 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 IR.

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