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

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. Methods: 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 matrixassisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Results: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean ± SD: TTR 3.96 ± 0.89 μ mol/L vs. 4.68 ± 1.21 μ mol/L, RBP4 1.13 ± 0.25 μ mol/L vs. 1.33 ± 0.38 μ mol/L and ROH 1.33 ± 0.17 μ mol/L vs. 1.62 ± 0.29 μ mol/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). Conclusions: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.