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We assessed the nature of the dose-response relationship between gamma-glutamyl transferase (GGT) levels and risk of incident type II diabetes mellitus (T2DM) in the general population.Systematic review and dose-response meta-analysis of published prospective studies. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science databases up to June 2014. We examined a potential nonlinear relationship using restricted cubic splines.Of the 300 titles reviewed, we included 24 cohort studies with data on 177,307 participants and 11,155 T2DM cases. In pooled analysis of 16 studies with relevant data, there was evidence of a nonlinear association between GGT and T2DM risk in both males (P for nonlinearity = .02) and females (P for nonlinearity = .0005). In a comparison of extreme thirds of baseline levels of GGT, relative risk for T2DM in pooled analysis of all 24 studies was 1.34 (95% confidence interval, 1.27-1.42). There was heterogeneity among the studies (P < .001), which was to a large part explained by blood sample used, study size, degree of confounder adjustment, and quality of studies.Circulating level of GGT contributes to an increased risk of T2DM in the general population in a nonlinear dose-response pattern.

Original publication




Journal article


Annals of epidemiology

Publication Date





809 - 816


Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Electronic address:


Humans, Diabetes Mellitus, Type 2, gamma-Glutamyltransferase, Risk Factors, Sex Factors, Adult, Aged, Middle Aged, Female, Male