γ-Glutamyltransferase Is a Predictor of Incident Diabetes and Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract

Background: ␥-Glutamyltransferase (GGT), which maintains cellular concentrations of glutathione, may be a marker of oxidative stress, and GGT itself may produce oxidative stress. We performed a prospective study to examine whether serum GGT predicts diabetes and hypertension. Methods: Study participants were 4844 black and white men and women 18 -30 years of age in 1985-1986; they were reexamined 2, 5, 7, 10, and 15 years later. Year 0 GGT cutpoints were 12, 17, 25, and 36 U/L (overall 25th, 50th, 75th, and 90th percentiles; the laboratory cutpoints for abnormal are 40 U/L in women and 50 U/L in men). We deleted 32 participants with prevalent diabetes and 140 participants with prevalent hypertension from the respective incidence analyses. Results: After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0 -8.1), and 5.5 (2.7-11.1) for 15-year incident diabetes and 1.

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

“…Furthermore, the association between serum GGT and type 2 diabetes was stronger among the obese, and obesity did not predict the risk of type 2 diabetes among participants with GGT levels at the low end of the normal range [1]. A similar pattern of associations was observed in datasets from the Coronary Artery Risk Development in Young Adults (CARDIA) study [2], the Finland Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (FinMONICA) study [3], the National Health and Nutrition Examination Survey (NHANES) [4], and in German women, but not men [5], leading us to search for new interpretations of serum GGT. Cellular GGT, found on the plasma membrane in most tissues [6], metabolises extracellular glutathione (GSH), the main intracellular antioxidant, allowing precursor amino acids to be reutilised for intracellular GSH re-synthesis [7]a process known as the 'γ-glutamyl cycle' (Fig.…”

“…Supporting this hypothesis, serum GGT is inversely associated with serum antioxidants [11] and positively associated with F 2 -isoprostanes and C-reactive protein [2].…”

“…These mechanisms may partly explain some of the associations between GGT and type 2 diabetes, especially those observed at relatively high levels of serum GGT activity. However, it is important that even a slight increase in serum GGT activity at the low end of the normal range, where hepatic steatosis is unlikely, increased the risk of type 2 diabetes [1][2][3]. Fig.…”

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels # †

“…[4][5][6][7][8][9][10] GGT levels also correlate positively with novel cardiovascular risk factors, such as CRP, 38 fibrinogen, F2-isoprostanes, 39 and inversely with antioxidant levels. 40 Thus, high GGT levels are suggested as an early marker of oxidative stress and inflammation, explaining various associations in the pathway of GGT-disease-mortality.…”

“…As development of diabetes is predicted by high GGT levels, 7,34 even if in its reference range, diagnosis of diabetes may mediate the revealed association between GGT and mortality. But inclusion of diabetes in a model that predicted all-cause mortality by elevated GGT levels did not affect the esti- mates, as well as inclusion of a summative CVD score.…”