Liver enzymes as a predictor for incident diabetes in a Japanese population: The Hisayama study

Objective: We studied the relationship between liver enzymes and the development of diabetes in a general Japanese population. Research Methods and Procedures: A total of 1804 non-diabetic subjects 40 to 79 years of age were followed-up prospectively for a mean of 9.0 years. Results: During the follow-up, 135 subjects developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly with elevating quartiles of serum γ-glutamyltransferase (GGT) and alanine aminotransferase (ALT) levels. This pattern was also observed in aspartate aminotransferase (AST) quartiles for men but not for women. In multivariate analyses after adjusting for comprehensive risk factors and other liver enzymes, the risk of developing diabetes was significantly higher in the highest GGT quartile than in the lowest quartile [odds ratio (OR), 2.54; 95% confidence interval (CI), 1.03 to 6.26 for men; OR, 5.73; 95% CI, 1.62 to 20.19 for women]. Similar results were observed in ALT quartiles (OR, 2.32; 95% CI, 0.91 to 5.92 for men; OR, 4.40; 95% CI, 1.38 to 14.06 for women) but not in AST quartiles in either sex. Significant positive associations of GGT and ALT with diabetes were seen within each stratified category of risk factors, namely fasting insulin, BMI, waist-to-hip ratio, high-sensitivity C-reactive protein, and alcohol consumption. In receiver operating characteristic analyses, the areas under the receiver operating characteristic curve of GGT and ALT were significantly larger than that of AST, fasting insulin, waist-to-hip ratio, or C-reactive protein. Discussion: Our findings suggest that serum GGT and ALT concentrations are strong predictors of diabetes in the general population, independent of known risk factors.