Aims/Hypothesis. Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes.

Methods. A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication.

Results. There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10–19, 20–29, 30–39, 40–49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration.

Conclusion/Interpretation. This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes.