Levels of alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) have been reported to be associated with increased risk of diabetes mellitus (DM). However, whether a combination of levels of ALT and GGT predicts new onset of DM better than does ALT or GGT alone in both males and females has not fully been addressed. We investigated the relationship between the combination of ALT and GGT and DM development during a 10-year follow-up period in 13,919 subjects (male/female: 8,983/4,936; age 48 ± 10 years) who received health examinations. During the 10-year period, 617 males (6.9%) and 153 females (3.1%) had new onset of DM. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios (HRs) of DM development increased with higher levels of ALT and GGT at baseline in both sexes after adjustment of confounding factors. When divided into 4 subgroups of high (H-) and low (L-) levels of ALT (male/female: 27/21 U/L) and GGT (male/female: 43/23 U/L) using cutoff values shown by receiver operating characteristic curve analyses, the adjusted HR in the H-ALT/H-GGT group was significantly higher than HR in the L-ALT/L-GGT group as the reference in males (HR [95% confidence interval]: 1.73[1.36–2.20], p < 0.001) but was not significantly higher in females (1.50 [0.97–2.33], p = 0.065). The addition of the combination of H-ALT/H-GGT to traditional risk factors with and without H-ALT or H-GGT alone significantly improved the discriminatory capability for predicting development of DM. In conclusion, the combination of H-ALT/H-GGT efficiently predicts development of DM in male individuals but not significantly in female individuals.

据报道，丙氨酸氨基转移酶 (ALT) 和 γ-谷氨酰转移酶 (GGT) 水平与糖尿病 (DM) 风险增加有关。然而，在男性和女性中，ALT 和 GGT 水平的组合是否比单独使用 ALT 或 GGT 更能预测新发 DM 尚未完全得到解决。我们在 13,919 名接受健康检查的受试者（男性/女性：8,983/4,936；年龄 48 ± 10 岁）的 10 年随访期间调查了 ALT 和 GGT 组合与 DM 发展之间的关系。在 10 年期间，617 名男性 (6.9%) 和 153 名女性 (3.1%) 新发 DM。具有受限三次样条的多变量 Cox 比例风险模型显示，在调整混杂因素后，DM 发展的风险比 (HR) 随着基线 ALT 和 GGT 水平的升高而增加。当使用所示的截止值分为高 (H-) 和低 (L-) ALT（男性/女性：27/21 U/L）和 GGT（男性/女性：43/23 U/L）水平的 4 个亚组时通过受试者工作特征曲线分析，H-ALT/H-GGT 组的调整 HR 显着高于 L-ALT/L-GGT 组作为男性参考的 HR（HR [95% 置信区间]：1.73 [1.36–2.20]，p < 0.001）但在女性中没有显着升高（1.50 [0.97–2.33]，p = 0.065）。将 H-ALT/H-GGT 的组合添加到传统的危险因素中，有和没有 H-ALT 或 H-GGT 单独显着提高了预测 DM 发展的辨别能力。总之，H-ALT/H-GGT 的组合有效地预测了男性个体中 DM 的发展，但在女性个体中并不显着。