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

• Published in: Diabetes care Vol. 30; no. 10; pp. 2673 - 2678
• Main Authors: WALLACE, Tara M, UTZSCHNEIDER, Kristina M, TONG, Jenny, CARR, Darcy B, ZRAIKA, Sakeneh, BANKSON, Daniel D, KNOPP, Robert H, KAHN, Steven E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2007
• Subjects: Adipose Tissue - physiology; Adult; Aged; Alanine Transaminase - blood; Aspartate Aminotransferases - blood; Biological and medical sciences; Body fat; Cardiovascular disease; Chemical properties; Diabetes; Diabetes. Impaired glucose tolerance; Diet; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzymes; Family trusts; Fat metabolism; Female; gamma-Glutamyltransferase - blood; Humans; Insulin; Insulin - pharmacology; Insulin Resistance; Liver diseases; Male; Medical research; Medical sciences; Metabolic diseases; Metabolic syndrome; Middle Aged; Miscellaneous; Mortality; Native North Americans; Obesity; Obesity - blood; Obesity - enzymology; Plasma; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reference Values; Thyroid diseases; Womens health; United States; Human; Pancreatic hormone; Adipose tissue; Nutrition; Digestive system; Enzyme; Liver; Metabolic diseases; Insulin; Fat mass; Visceral obesity; Abdomen; Endocrinology
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc06-1758

Relationship of Liver Enzymes to Insulin Sensitivity and Intra-Abdominal Fat Tara M. Wallace , MD 1 , Kristina M. Utzschneider , MD 1 , Jenny Tong , MD 1 , Darcy B. Carr , MD 2 , Sakeneh Zraika , PHD 1 , Daniel D. Bankson , MD 3 , Robert H. Knopp , MD 4 and Steven E. Kahn , MB, CHB 1 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 Abstract 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 γ-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/m 2 ) and S I (< or ≥7.0 × 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. ALT, alanine aminotransferase AST, aspartate aminotransferase FSIGT, frequently sampled intravenous glucose tolerance test GGT, γ-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 SI, insulin sensitivity index WHR, waist-to-hip ratio Footnotes Published ahead of print at http://care.diabetesjournals.org on 31 July 2007. DOI: 10.2337/dc06-1758. T.M.W., K.M.U., and J.T. contributed equally to this work. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact. Accepted June 29, 2007. Received August 18, 2006. DIABETES CARE