The risk for preeclampsia (PE) is increased 4-fold in women with type 1 diabetes (T1D), in whom we previously demonstrated that elevated cholesterol-rich lipoproteins confer risk at the 1st trimester. Sphingolipids, including ceramides (Cer) and glycosphingolipids (hexosyl- (HexCer) and lactosyl-ceramides (LacCer)), are lipoprotein constituents that regulate cell signaling. We propose that these bio-active lipids could be modulators of PE risk.
In a prospective T1D pregnancy cohort (studied at 12, 22, 32 weeks’ gestation), we used liquid chromatography/electrospray ionization-tandem mass spectrometry to determine plasma levels of 12 species of Cer, HexCer, and LacCer in 23 women with T1DM who did vs. 24 who did not develop PE, and in 19 normotensive nondiabetic pregnant women. All were free of microalbuminuria and hypertension at enrolment; all visits preceded clinical PE onset.
Results: Plasma levels of C22-Cer (1st and 3rd study visits); C26:1-Cer (1st and 2nd visits); C26-Cer (1st visit); C18-Cer and C18:1-Cer (2nd visit) were significantly higher in women with T1DM who did vs. did not develop PE. C22-Cer and C26-Cer were significantly lower in T1DM vs. non-T1DM (1st visit). There were no overall PE- or diabetes-related differences in any HexCer- or LacCer species. Longitudinally, most Cer and HexCer species increased throughout pregnancy in all groups (except C14- and C18-Cer; and C14 and C26-HexCer). C16-LacCer increased, while C22:1-, C26-, and C26:1-LacCer decreased as pregnancy advanced, independent of PE status. Independent of LDL-C, total Cer increased throughout pregnancy in all groups.
Conclusions: Maternal Cer species may serve as early biomarkers for PE in women with T1DM. T1DM was associated with lower levels of two Cer species. Like cholesterol-rich lipoproteins, Cer, HexCer and some LacCer species increase as pregnancy advances in all groups, but other LacCer species decrease: the significance of these findings requires further study.
C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None.
JDRF; Novo Nordisk; National Institutes of Health