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

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.