Macrophage inhibitory cytokine-1 is increased in individuals before type 2 diabetes diagnosis but is not an independent predictor of type 2 diabetes: the Whitehall II study

摘要

Objective Macrophage inhibitory cytokine-1 (MIC-1) belongs to the transforming growth factor (TGF)-β superfamily, and has been reported to be involved in energy homoeostasis and weight loss and to have anti-inflammatory properties. We hypothesized that decreased concentrations of MIC-1 would be associated with higher risk of developing type 2 diabetes. Design and methods We designed a nested case–control study within the Whitehall II cohort and measured serum concentrations of MIC-1 by ELISA in 180 individuals without type 2 diabetes at baseline who developed type 2 diabetes during the follow-up period of 11.5±3.0 years and in 372 controls frequency-matched for age, sex, and body mass index with normal glucose tolerance throughout the study. Results MIC-1 concentrations at baseline were higher in cases (median (25/75th percentiles) 537.1 (452.7–677.4) pg/ml) than in controls (499.7 (413.8–615.4) pg/ml; P=0.0044). In the age- and sex-adjusted model, a 1-s.d. increase in MIC-1 (206.0 pg/ml) was associated with an odds ratio (95% confidence interval) of 1.21 (0.997; 1.46; P=0.054) for type 2 diabetes. Adjustment for waist circumference, cardiovascular risk factors, socioeconomic status, proinflammatory mediators, and glycemia abolished the association. Conclusions Baseline MIC-1 concentrations were increased, not decreased, in individuals before type 2 diabetes manifestation, but not independently associated with incident type 2 diabetes in multivariable analyses. This upregulation of MIC-1 could be part of an anti-inflammatory response preceding the onset of type 2 diabetes, which has been described before for interleukin-1 receptor antagonist and TGF-β1.