First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus

Abstract

The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy. Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean±SD: TTR 3.96±0.89 μmol/L vs. 4.68±1.21 μmol/L, RBP4 1.13±0.25 μmol/L vs. 1.33±0.38 μmol/L and ROH 1.33±0.17 μmol/L vs. 1.62±0.29 μmol/L, p<0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p<0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95% CI 0.87–0.98, p<0.05). First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.