Haptoglobin phenotype, pre-eclampsia, and response to supplementation with vitamins C and E in pregnant women with type-1 diabetes

Abstract

Objective: The phenotype of the antioxidant and pro-angiogenic protein haptoglobin (Hp) predicts cardiovascular disease risk and treatment response to antioxidant vitamins in individuals with diabetes. Our objective was to determine whether Hp phenotype influences pre-eclampsia risk, or the efficacy of vitamins C and E in preventing pre-eclampsia, in women with type-1 diabetes.

Design: This is a secondary analysis of a randomised controlled trial in which women with diabetes received daily vitamins C and E, or placebo, from 8 to 22 weeks of gestation until delivery.

Setting: Twenty-five antenatal metabolic clinics across the UK (in north-west England, Scotland, and Northern Ireland).

Population: Pregnant women with type-1 diabetes.

Methods: Hp phenotype was determined in white women who completed the study and had plasma samples available (n = 685).

Main outcome measure: Pre-eclampsia.

Results: Compared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30-1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60-1.45) were not associated with significantly decreased pre-eclampsia risk after adjusting for treatment group and HbA1c at randomisation. Our study was not powered to detect an interaction between Hp phenotype and treatment response; however, our preliminary analysis suggests that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95% CI 0.22-2.71; Hp 2-1, OR 0.81, 95% CI 0.46-1.43; Hp 2-2, 0.67, 95% CI 0.34-1.33), after adjusting for HbA1c at randomisation.

Conclusions: The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.

Keywords: Haptoglobin phenotype; pre-eclampsia; pregnancy; type-1 diabetes; vitamin C; vitamin E.

Figure 1. Hp phenotypes by Native and SDS PAGE

Panel A: Hp phenotyping of Hb-supplemented plasma by Native PAGE on a 6% gel using Hb peroxidase detection. Hp 1-1 has a single fast migrating band (Lane 2). Hp 2-2 has a series of slowly migrating bands (Lane 6). Hp 2-1 (Lanes 1, 3–5) has one band between the Hb/Hp 1-1 and Hb/Hp 2-2 bands, and several slowly migrating bands in the same region as the Hb/Hp 2-2 bands. Panel B: Hp phenotyping of plasma by SDS PAGE on a 12% gel with Western blotting. All phenotypes have the Hp β band. The α₁ band indicates that the Hp 1 allele is present. The α₂ band indicates that the Hp 2 allele is present. Hp 2-2 has α₂ and β bands (Lane 1), Hp 2-1 has α₁, α₂ and β bands (Lane 2), and Hp 1-1 has α₁ and β bands (Lane 3).