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

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 0.301.16) 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 preeclampsia 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 preeclampsia risk in women with type-1 diabetes.