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Relationship of Liver Enzymes to Insulin Sensitivity and Intra-Abdominal Fat

¹ Department of Medicine, VA Puget Sound Health Care System, and University of Washington, Seattle, Washington
² Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington
³ Department of Pathology and Laboratory Medicine, VA Puget Sound Health Care System, and University of Washington, Seattle, Washington
⁴ Harborview Medical Center, University of Washington, Seattle, Washington

Address correspondence and reprint requests to Steven E. Kahn, MB, ChB, VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108. E-mail: skahn{at}u.washington.edu

OBJECTIVE— The purpose of this study was to determine the relationship between plasma liver enzyme concentrations, insulin sensitivity, and intra-abdominal fat (IAF) distribution.

RESEARCH DESIGN AND METHODS— Plasma -glutamyl transferase (GGT), aspartate transaminase (AST), alanine transaminase (ALT) levels, insulin sensitivity (insulin sensitivity index [S_I]), IAF area, and subcutaneous fat (SCF) area were measured in 177 nondiabetic subjects (75 men and 102 women, aged 31–75 years) with no history of liver disease. On the basis of BMI (< or 27.5 kg/m²) and S_I (< or 7.0 x 10^–5 min/pmol) subjects were divided into lean insulin sensitive (LIS, n = 53), lean insulin resistant (LIR, n = 60), and obese insulin resistant (OIR, n = 56) groups.

RESULTS— Levels of all three liver enzymes were higher in men than in women (P < 0.0001 for each). In men, GGT levels were higher in insulin-resistant than in insulin-sensitive subjects (P < 0.01). In women, GGT levels were higher in the OIR than in the LIS group (P < 0.01) but no different in the LIR group. There was no difference in ALT and AST levels among the LIS, LIR, and OIR groups. GGT was associated with S_I (r = –0.26, P < 0.0001), IAF area (r = 0.22, P < 0.01), waist-to-hip ratio (WHR) (r = 0.25, P = 0.001), BMI (r = 0.17, P < 0.05), and SCF area (r = 0.16, P < 0.05) after adjustments for age and sex. In men, only S_I (r = –0.29, P < 0.05) remained independently correlated with GGT in multiple regression analysis. In women, IAF area (r = 0.29, P < 0.01) and WHR (r = 0.29, P < 0.01) were independently associated with GGT, but S_I was not.

CONCLUSIONS— In nondiabetic men GGT but not AST or ALT levels, are inversely related to insulin sensitivity independent of IAF area. However in women, GGT is related to measures of central body fat rather than to insulin sensitivity.

Abbreviations: ALT, alanine aminotransferase • AST, aspartate aminotransferase • FSIGT, frequently sampled intravenous glucose tolerance test • GGT, -glutamyl transferase • IAF, intra-abdominal fat • IQR, interquartile range • LIR, lean insulin resistant • LIS, lean insulin sensitive • NAFLD, nonalcoholic fatty liver disease • NASH, nonalcoholic steatohepatitis • OIR, obese insulin resistant • SCF, subcutaneous fat • S_I, insulin sensitivity index • WHR, waist-to-hip ratio

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