Vitamin D metabolites and binding protein predict preeclampsia in women
with Type 1 diabetes: a cohort study
Abstract
Objective: Preeclampsia (PE) occurs about four times more frequently in
women with than without diabetes. Vitamin D is essential for healthy
pregnancy. We investigated detailed measures of maternal plasma
25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D
(1,25(OH)2D), and vitamin D binding protein (VDBP) to
define associations with PE in women with Type 1 diabetes (T1DM). Design
and setting: A multicentre prospective study in women at
~12, ~22 and ~32 weeks’
gestation (‘Visits’ (V) 1, 2, and 3, respectively). Population: We
studied 23 T1DM women who subsequently developed PE, 24 who remained
normotensive, and 19 non-diabetic, normotensive women (reference
controls). Diabetic women were complication-free at V1, and all study
visits preceded PE onset. Main Outcome Measures: Total, bioavailable,
and free concentrations of 25(OH)D and 1,25(OH)2D; and
VDBP. Results: 25(OH)D deficiency was more frequent in diabetic than
non-diabetic women (69% vs 22%, p<0.05), but no measure of
25(OH)D predicted PE. In contrast, higher 1,25(OH)2D
concentrations at V2 (total and bioavailable: p<0.01; free:
p<0.05) and V3 (bioavailable: p<0.05; free:
p<0.01) were associated with subsequent PE in T1DM women, as
were lower concentrations of VDBP at V3 (p<0.05) and elevated
ratios of 1,25(OH)2D/VDBP (V2, V3: p<0.01) and
1,25(OH)2D/25(OH)D (V3, p<0.05). Significance
persisted after adjustment for covariates. Conclusions:In women with
T1DM, concentrations of active vitamin D were higher, and VDBP lower, in
the second and third trimesters in those who developed PE than in those
who did not. Active vitamin D may serve as a new marker for PE risk, and
could be implicated in pathogenesis.