Association between liver enzymes and incident type 2 diabetes in Singapore Chinese men and women

AIMS To assess the association between liver enzymes and the risk of type 2 diabetes (T2D) in a Chinese population. METHODS A nested case-control study comprising 571 T2D cases and 571 matched controls was conducted within the Singapore Chinese Health Study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were quantified in baseline plasma collected from them, while γ-glutamyltransferase (GGT) was assayed among 255 T2D cases with baseline hemoglobin A1c <6.5% and 255 matched controls. Participants were free of diagnosed diabetes, cardiovascular disease, and cancer at blood collections (1999-2004). Incident self-reported T2D cases were identified at follow-up II interview (2006-2010). Controls were matched to cases on age, sex, dialect group, and date of blood collection. RESULTS Higher levels of ALT and GGT were significantly associated with increased risk of T2D (p for trend <0.001 for ALT, p for trend=0.03 for GGT), and the ORs (95% CIs) comparing highest versus lowest tertiles of ALT and GGT were 2.00 (1.01 to 3.96) and 2.38 (1.21 to 4.66), respectively. A null association was observed for AST, ALP, and LDH with T2D risk. Adding GGT (<23 vs ≥23 IU/L) or ALT (<21 vs ≥21 IU/L) to a prediction model resulted in significant gain in net reclassification improvement and integrated discrimination improvement of T2D prediction (all p<0.001). CONCLUSIONS Higher levels of GGT and ALT are associated with increased T2D risk. GGT ≥23 IU/L and ALT ≥21 IU/L may identify people at higher risk of developing T2D in this Chinese population.