Haptoglobin Concentration, Pregnancy, and Preeclampsia in Women with Type 1 Diabetes

Abstract

Haptoglobin (Hp) binds the globin portion of free haemoglobin (Hb) thus inhibiting oxidative damage: it also has anti-inflammatory and pro-angiogenic properties. There are two Hp alleles and three phenotypes, Hp 1-1, Hp 2-1, and Hp 2-2; the latter is present in ∼50% of people, and is associated with cardiovascular risk and declining renal function in diabetes patients. Preeclampsia (PE) occurs more frequently in diabetic than nondiabetic women (∼20% vs. ∼5%): reasons are not fully elucidated, but oxidative stress, inflammation, and altered angiogenesis are implicated. We determined maternal plasma Hp levels (ELISA, R and D Systems) and Hp phenotype (ELISA, Savyon Diagnostics Ltd.) in a prospective study of 23 pregnant women with type 1 diabetes (T1D) who developed PE, 24 who remained normotensive, and 19 pregnant normotensive nondiabetic women. Samples were collected at 3 visits (V1-V3) (12.4 ± 1.8, 21.7 ± 1.4, and 31.3 ± 1.4 weeks gestation (mean ± SD)). All subjects were free of microalbuminuria and hypertension at enrolment, and all visits preceded clinical PE onset. Results: Longitudinal analyses revealed significant temporal decreases of plasma Hp during pregnancy in T1D women who developed PE (p=0.001) and in nondiabetic normotensive women (p=0.017), but not in T1D who remained normotensive. Among all T1D women, plasma Hp was lower in those with Hp 2-2 vs. ’non-Hp 2-2’ phenotype at V2 (p=0.005) and V3 (p=0.002), independent of PE status. In Hp 2-2 T1D women only, plasma Hp was higher in those who did vs. did not develop PE at V1 (77.0 ± 31.4 vs. 50.7 ± 14.5 (mg/dl)) (p=0.033) and V2 (61.9 ± 19.0 vs. 42.0 ± 21.5) (p=0.046). Plasma Hp correlated positively with CRP at all visits (p<0.01), but not with previously-measured anti-angiogenic/angiogenic factors. Conclusion: Maternal plasma Hp may serve as an early marker for PE in T1D pregnancy, particularly in women with the Hp 2-2 phenotype. Disclosure C.B. Kelly: None. J. Yu: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US. Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations, Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Novo Nordisk A/S. C.E. Aston: None. T. Lyons: None.