Abstract. Nakanishi N, Nishina K, Li W, Sato M, Suzuki K, Tatara K (Osaka University Graduate School of Medicine, Osaka; and Japan Labor and Welfare Association, Tokyo; Japan). Serum c-glutamyltransferase and development of impaired fasting glucose or type 2 diabetes in middle-aged Japanese men. J Intern Med 2003; 254: 287-295.Objective. To investigate the association between serum c-glutamyltransferase (GGT) and risk for development of diabetes. Design. Longitudinal study (followed from 1994 to 2001). Setting. A work site in Japan. Subjects. A total of 2918 Japanese male office workers aged 35-59 years who did not have impaired fasting glucose (IFG) (a fasting plasma glucose concentration of 6.1-6.9 mmol L )1 ), type 2 diabetes (a fasting plasma glucose concentration of P7.0 mmol L )1 or receipt of hypoglycaemic medication), medication for hypertension or hepatitis, alanine aminotransferase concentrations higher than three times the upper limit of the reference range or a history of cardiovascular disease at study entry. Main outcome measure. Incidence of IFG or type 2 diabetes over a 7-year period.Results. With adjustment for potential risk factors for diabetes, the relative risk for IFG compared with serum GGT <16 U L )1 was 1.23 (95% CI, 0.79-1.90), 1.50 (CI, 0.97-2.32) and 1.70 (CI, 1.07-2.71) with serum GGT of 16-24, 25-43 and P44 U L )1 , respectively (P for trend ¼ 0.014). The respective relative risks for type 2 diabetes compared with serum GGT <16 U L )1 were 2.54 (CI, 1.29-5.01), 2.64 (CI, 1.33-5.23) and 3.44 (CI, 1.69-6.70) (P for trend ¼ 0.002). From stratified analyses by body mass index (BMI) and alcohol intake, a stronger linear association between serum GGT and development of IFG or type 2 diabetes was found in men with a BMI P23.2 kg m )2 in both those who drank <46 and P46 g day )1 of ethanol. Conclusions. The risk for development of IFG or type 2 diabetes increased in a dose-dependent manner as serum GGT increased in middle-aged Japanese men. The increased relative risk for IFG or type 2 diabetes associated with serum GGT was more pronounced in obese men.