Alanine aminotransferase and risk of the metabolic syndrome: a linear dose-response relationship.

Abstract

BackgroundElevated baseline circulating alanine aminotransferase (ALT) level has been demonstrated to be associated with an increased risk of the metabolic syndrome (MetS), but the nature of the dose-response relationship is uncertain.MethodsWe performed a systematic review and meta-analysis of published prospective cohort studies to characterize in detail the nature of the dose-response relationship between baseline ALT level and risk of incident MetS in the general population. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Prospective studies in which investigators reported relative risks (RRs) of MetS for 3 or more categories of ALT levels were eligible. A potential nonlinear relationship between ALT levels and MetS was examined using restricted cubic splines.ResultsOf the 489 studies reviewed, relevant data were available on 29,815 non-overlapping participants comprising 2,125 incident MetS events from five prospective cohort studies. There was evidence of a linear association (P for nonlinearity=0.38) between ALT level and risk of MetS, characterised by a graded increase in MetS risk at ALT levels 6-40 U/L. The risk of MetS increased by 14% for every 5 U/L increment in circulating ALT level (95% CI: 12-17%). Evidence was lacking of heterogeneity and publication bias among the contributing studies.ConclusionsBaseline ALT level is associated with risk of the MetS in a linear dose-response manner. Studies are needed to determine whether the association represents a causal relationship.