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 ( H p) predicts cardiovascular disease risk and treatment response to antioxidant vitamins in individuals with diabetes. Our objective was to determine whether H p 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 E ngland, S cotland, and N orthern I reland). Population Pregnant women with type‐1 diabetes. Methods H p 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 H p 2‐1, H p 1‐1 ( OR 0.59, 95% CI 0.30–1.16) and H p 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 H b A 1c at randomisation. Our study was not powered to detect an interaction between H p phenotype and treatment response; however, our preliminary analysis suggests that vitamins C and E did not prevent pre‐eclampsia in women of any H p phenotype ( H p 1‐1, OR 0.77, 95% CI 0.22–2.71; H p 2‐1, OR 0.81, 95% CI 0.46–1.43; H p 2‐2, 0.67, 95% CI 0.34–1.33), after adjusting for H b A 1c at randomisation. Conclusions The H p phenotype did not significantly affect pre‐eclampsia risk in women with type‐1 diabetes.