Association of fetuin-A with incident type 2 diabetes: results from the MONICA/KORA Augsburg study and a systematic meta-analysis

Abstract

Objective We investigated the association of circulating fetuin-A with incident T2D particularly examining potential sex differences. Additionally, we determined whether putative associations were independent of subclinical inflammation, adiponectin and liver fat content. Design Case-cohort study plus systematic meta-analysis. Methods We investigated the association between baseline fetuin-A levels and incident T2D in the MONICA/KORA Augsburg study using Cox proportional hazards analyses. Furthermore, we conducted a systematic review within PubMed and EMBASE and pooled association estimates of eligible studies with the MONICA/KORA Augsburg data using a DerSimonian-Laird random effects model. Results Within MONICA/KORA Augsburg, 930 participants developed incident T2D (median follow-up: 14 years). We observed a significant association between fetuin-A and T2D risk after multivariable adjustment including C-reactive protein and adiponectin. The strength of the association was similar in males and females (P value for sex interaction >0.55). Seven eligible published studies were identified in addition to the MONICA/KORA Augsburg study for the meta-analysis. The pooled hazard ratio (95% CI) for incident T2D per 1 standard deviation (s.d.) increment of fetuin-A was 1.24 (1.14–1.34) for the multivariable adjusted model. Our sex-stratified meta-analysis yielded relative risk estimates per 1 s.d. of 1.19 (1.04–1.38) in males and 1.29 (1.15–1.46) in females. Further individual adjustment for subclinical inflammation, adiponectin and liver fat content had almost no impact on the strength of the association. Conclusions Higher fetuin-A levels are associated with incident T2D in both males and females independently of subclinical inflammation, adiponectin and liver fat content.