Maternal Plasma Ages And Preeclampsia In Women With Type 1 Diabetes

Preeclampsia (PE) occurs four times more frequently in pregnant women with type 1 diabetes (T1D) than in nondiabetic women. We hypothesized that elevated plasma advanced glycoxidation products (AGEs) predict PE in T1D women. In a prospective T1D pregnancy cohort (study visits at 12, 22, 32 weeks' gestation), we used liquid chromatography/mass spectrometry, with internal stable heavy isotope substituted standards, to determine plasma levels of nine AGE and oxidation products (carboxymethyl-lysine [CML], carboxyethyl-lysine [CEL], methylglyoxal-hydroimidazolone [MGHI], 3-deoxyglucosone hydroimidazolones [3DGH], methionine sulfoxide [MetSO], glyoxal hydroimidazolone [GHI], 3-nitrotyrosine [3NT], dityrosine [DT], 2-aminoadipic acid [2AAA]) in 23 women with T1DM who developed PE vs. 24 who did not, and in 19 nondiabetic normotensive pregnant women. These products have been associated with CVD and renal failure in non-pregnant cohorts. All women were free of microalbuminuria and hypertension at enrolment, and all visits preceded clinical PE onset. GFR was estimated (Chronic Kidney Disease Epidemiology Collaboration equation). Results: Plasma CML, CEL, MGHI, 3DGH, MetSO, GHI, and 2AAA did not differ between the three groups at any study visit, and thus did not predict preeclampsia in T1D. In T1D women who later developed PE, eGFR was inversely associated at V3 with CML (p=0.008), CEL (p=0.03), MGH1 (p=0.03), 3DGH (p=0.03), GHI (p<0.001), and 2AAA (p<0.05); and at V2 with CEL (p=0.04), MGHI (p=0.02), and GHI (p=0.02). No such associations were observed in normotensive T1D or in nondiabetic pregnant women. Plasma levels of 3NT and DT were undetectable in all participants. Conclusions: Plasma AGEs did not predict PE in well-controlled, previously healthy T1D women, and levels did not differ from healthy nondiabetic controls. Uniquely, in T1D women who developed PE, plasma AGEs were associated with renal function, consistent with the notion that subclinical alterations in renal function precede PE. Disclosure H. Karanchi: None. 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. C.E. Aston: None. S. Howell: Employee; Self; PreventAGE Health Care, LLC. P.J. Beisswenger: Other Relationship; Self; PreventAGE Health Care, LLC. T. Lyons: None.