Combined effect of serum alanine aminotransferase and gamma-glutamyltransferase on incidence of diabetes mellitus: A longitudinal study

Abstract

High levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are associated with increased diabetes risk. In the present study, we investigated the combined effects of ALT and GGT on the development of diabetes in a Korean population. A total of 9405 individuals (4020 women and 5385 men) without diabetes were enrolled in this study. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in ALT and GGT quartile levels, was analyzed. In addition, we analyzed the quartiles of ALT and GGT together to determine any synergistic effect from the fourth quartile of ALT and GGT on the development of diabetes. The development of diabetes gradually increased with an increase in the circulating levels of ALT and GGT. For the fourth quartile ALT and GGT, the hazard ratios of diabetes compared with the first quartile were 1.892 (95% confidence interval [CI]: 1.26-2.83, P = .002) and 3.526 (95% CI: 2.12-5.85, P < .001) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both fourth quartiles of ALT and GGT were 3.663 (95% CI: 2.42-5.52, P < .001), as compared with the first and second quartiles. Serum ALT and GGT levels are well associated with diabetes in Koreans after adjusting for confounders, and a combination of ALT and GGT levels can have a synergy in predicting the development of diabetes.

Figure 1

Adjusted hazard ratios^∗ (95% confidence interval; P) of the development of diabetes mellitus according to the combined categories of ALT and GGT levels (1st and 2nd quartile, 3rd quartile, and 4th quartile). The reference category consisted of the 1st and 2nd quartile of ALT and GGT levels. Interaction terms for ALT and GGT combinations were statistically significant (P < .001). ALT = alanine aminotransferase, BMI = body mass index, GGT = gamma-glutamyltransferase. ^∗The model was adjusted for age, sex, BMI = log-transformed weekly alcohol consumption, fasting glucose, current smoker, hypertension, dyslipidemia, and uric acid.