Serum [Gamma]-Glutamyltransferase was Differently Associated with Microalbuminuria by Status of Hypertension Or Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study (Lipids, Lipoproteins, And Cardiovascular Risk Factors)

Serum [gamma]-glutamyltransferase (GGT) [5] concentrations within the physiologic range have been strongly associated with most cardiovascular disease risk factors and predicted the development of heart disease, hypertension, stroke, and type 2 diabetes (1-6). In particular, serum GGT concentrations have shown a strong graded relationship with incident diabetes, suggesting a role in the pathogenesis of diabetes (2, 3). Although serum GGT activity has commonly been used as a marker for excessive alcohol consumption or liver diseases (7), neither alcohol consumption nor liver dysfunction likely explain the association between serum GGT and diabetes (2, 3). A series of Coronary Artery Risk Development [gamma] Adults (CARDIA) studies (3, 8, 9) suggested that oxidative stress might explain these associations because serum GGT within the physiologic range had dose-response relationships with serum and/or dietary antioxidant vitamins and markers of oxidative stress such as [F.sub.2]-isoprostanes. Although the relationship between cellular GGT and serum GGT is not known, cellular GGT has been known to play an important role in antioxidant defense systems (10-12); paradoxically, cellular GGT may also be involved in the generation of reactive oxygen species in the presence of transition metals (13-16). Recently, a role of serum GGT as an early and sensitive marker of oxidative stress was reviewed (17). Microalbuminuria, slightly increased albumin excretion in the urine, is now considered to be a predictor of atherosclerotic diseases (18,19). Recent evidence strongly suggested that microalbuminuria is an independent predictor of cardiovascular disease in diabetic or hypertensive patients, in elderly patients, and in the general population (18,19). The mechanisms linking microalbuminuria and risk for cardiovascular disease are not fully understood; a recent concept is that microalbuminuria is a marker of endothelial dysfunction (18,19). Generalized endothelial dysfunction has been hypothesized to be the underlying factor for microalbuminuria on the one hand and the underlying factor for increased cardiovascular risk on the other. Accumulating evidence suggests that oxidative stress alters many functions of the endothelium, including modulation of vasomotor tone (20).