AIM: It has been shown, mainly in men, that gamma-glutamyltransferase (gammaGT) and alanine-aminotransferase (ALT) predict the development of type 2 diabetes. This study investigates the association between hepatic markers and the 3-year risk of diabetes. METHODS: Incident diabetes was studied in 2071 men and 2130 women without diabetes at baseline from the D.E.S.I.R. cohort. RESULTS: Adjusting on age, only gammaGT was predictive of diabetes in both sexes, whereas ALT and aspartate-aminotransferase (AST) were only predictive in men, and bilirubin was not predictive. After adjustment on classical confounding factors and on ALT activity, the odds ratios (OR) for incident diabetes increased across baseline gammaGT quartiles: 1, 3.1, 2.6, 5.0 in men (P<0.0003) and 1, 0.9, 3.2, 3.5 in women (P<0.01). The relations with ALT and AST were not significant after adjusting on gammaGT. Additional adjustment on markers of insulin resistance, BMI or fasting plasma glucose attenuated the risk associated with gammaGT in both sexes, and it remained significantly predictive only in the men. Pooling men and women, those with gammaGT above the median had adjusted ORs of developing diabetes of 13.7 (1.8-99.8) if WHR > =0.85 and 1.7 (0.6-4.8) if WHR<0.85 (interaction P<0.007). CONCLUSION: gammaGT was the main hepatic risk marker for type-2 diabetes in both sexes, especially in subjects with central adiposity.