Zhao Wei, Tong Jingjing, Liu Jie, Liu Jin, Li Jinghua, Cao Yongtong
Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, China.
Liver Failure Treatment and Research Center, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China.
Int J Endocrinol. 2020 Feb 21;2020:5356498. doi: 10.1155/2020/5356498. eCollection 2020.
The purpose of this study was to examine the association between baseline serum gamma-glutamyl transferase (GGT) and incident diabetes mellitus and to explore their dose-response relationship in a cohort of Japanese adults. . Data were drawn from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study between 2004 and 2015, including hierarchical information on participants ≥18 years of age without diabetes mellitus, preexisting diabetes mellitus, heavy alcohol drinking, or other liver diseases (e.g., hepatitis B/C). The final analytic sample included 15464 participants, 373 of who were diagnosed as diabetes mellitus with a maximum 13-year follow-up. The risk of incident diabetes mellitus according to baseline serum GGT was estimated using multivariable Cox proportional hazards models and a two-piecewise linear regression model was developed to find out the threshold effect.
Being in the highest quintile versus the lowest quintile of GGT levels was associated with an almost twofold increased risk of incident diabetes mellitus (hazard ratio 1.83 (95% CI 1.06, 3.15)), independent of age, gender, smoking status, alcohol intake, BMI, SBP, triglycerides, fatty liver, ALT, AST, and fasting plasma glucose. Further analysis revealed a positive curvilinear association between GGT and incident diabetes mellitus, with a saturation effect predicted at 24 IU/L. When serum GGT level was less than 24 IU/L, the risk of developing diabetes mellitus increased significantly with an increase in serum GGT levels (HR 1.04 (1.02, 1.07), =0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers (=0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers ( for interaction = 0.0378).
Serum GGT level was a significant predictor of subsequent risk of diabetes mellitus, which increased by 4% for every 1 IU/L increase in GGT when GGT was less than 24 IU/L.
本研究旨在探讨基线血清γ-谷氨酰转移酶（GGT）与新发糖尿病之间的关联，并在一组日本成年人队列中探究它们的剂量反应关系。数据取自2004年至2015年的NAGALA（岐阜地区非酒精性脂肪性肝病纵向分析）研究，包括年龄≥18岁、无糖尿病、无糖尿病前期、无大量饮酒或其他肝脏疾病（如乙型/丙型肝炎）的参与者的分层信息。最终分析样本包括15464名参与者，其中373人在最长13年的随访中被诊断为糖尿病。使用多变量Cox比例风险模型估计根据基线血清GGT发生糖尿病的风险，并建立了一个两段式线性回归模型以找出阈值效应。
与GGT水平最低五分位数相比，处于最高五分位数与新发糖尿病风险几乎增加两倍相关（风险比1.83（95%可信区间1.06, 3.15）），独立于年龄、性别、吸烟状况、酒精摄入量、体重指数、收缩压、甘油三酯、脂肪肝、丙氨酸转氨酶、天冬氨酸转氨酶和空腹血糖。进一步分析显示GGT与新发糖尿病之间呈正曲线关联，预测在24 IU/L时出现饱和效应。当血清GGT水平低于24 IU/L时，患糖尿病的风险随着血清GGT水平的升高而显著增加（风险比1.04（1.02, 1.07），P = 0.0017）。此外，这种关联在非吸烟参与者中比曾经吸烟或当前吸烟的参与者更显著（交互作用P = 0.0378）。
血清GGT水平是后续糖尿病风险的显著预测指标，当GGT低于24 IU/L时，GGT每升高1 IU/L，糖尿病风险增加4%。
