Hepatic Enzymes, the Metabolic Syndrome, and the Risk of Type 2 Diabetes in Older Men

Abstract

OBJECTIVE—We have examined the relationship between hepatic enzymes, the metabolic syndrome, insulin resistance, and type 2 diabetes and assessed the potential of hepatic enzyme measurements in determining diabetes risk. RESEARCH DESIGN AND METHODS—We conducted a prospective study of 3,500 nondiabetic men aged 60–79 years who were followed-up for a mean period of 5 years and in whom there were 100 incident type 2 diabetes cases. RESULTS—In cross-sectional analyses, alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) were strongly associated with obesity, insulin resistance, and the metabolic syndrome. Prospectively, the risk of type 2 diabetes significantly increased with increasing levels of ALT and GGT even after adjustment for confounders including BMI (top versus bottom quarter ALT: relative risk 2.72 [95% CI 1.47–5.02]; GGT: 3.68 [1.68–8.04]). Additional adjustment for insulin resistance attenuated the effects, but the relationships with ALT and GGT remained significant (1.91 [1.01–3.60] and 2.69 [1.21–5.97], respectively). Further adjustment for inflammatory markers (C-reactive protein) made minor differences. Among high-risk subjects (obese men or those with the metabolic syndrome), elevated GGT and ALT enhanced the prediction of diabetes risk. CONCLUSIONS— Elevated levels of ALT and GGT within the normal range are independent predictors of type 2 diabetes in older men and are useful additional measures in identifying those at high risk of diabetes.