Adequate levels of vitamin D are essential for bone health, immune
function, proliferation and differentiation of cells, inflammation,
insulin secretion and action, and vascular health.1Vitamin D deficiency is common worldwide, involving genetic, lifestyle
and geographical factors.1, 2 Vitamin D metabolism is
markedly altered during pregnancy. Specifically, for reasons not fully
understood, the active metabolite 1,25-dihydroxyvitamin D
(1,25(OH)2D) increases 2-3 fold in the first trimester,
reaching concentrations that would normally be toxic, and continues to
increase as pregnancy advances.3-5 Associations of
active vitamin D levels with preeclampsia (PE) in the presence of
maternal diabetes have not been investigated.
In the general population, the serum concentration of 25-hydroxyvitamin
D (25(OH)D), the prohormone and precursor of ‘active’
1,25(OH)2D, is considered the principal metric to assess
vitamin D status: deficiency and insufficiency are defined as
<20 and <32 ng/mL (50 and 80 nmol/L),
respectively.6 Vitamin D deficiency is associated with
poor pregnancy outcomes for both mother and child.2,
7-20
PE is a multisystem disorder defined by hypertension and proteinuria or
other end-organ dysfunction, with onset after 20 weeks’ gestation in a
previously normotensive woman.21 Women with type 1
diabetes (T1DM) have a markedly increased risk for PE
(~20% vs ~5% in the general
population).22 Vitamin D deficiency is associated with
abnormal placentation, altered angiogenesis, immune dysfunction, insulin
secretion and action, adverse lipid profiles, and inflammation: problems
that are also associated with diabetes.2, 4, 10, 12-16,
18, 23 Vitamin D deficiency may also be implicated in
PE.8, 12
We previously reported associations between PE and concentrations of
fat-soluble vitamins and antioxidant pro-vitamins in women with type 1
diabetes.24 In that study, we performed only one
measure of vitamin D status, 25(OH)D measured by HPLC. Women with T1DM
were more likely to be vitamin D deficient than the non-diabetic group,
but almost all diabetic women were deficient, and concentrations did not
differ significantly according to subsequent PE
status.24 Extending that work, we now investigate
whether total, bioavailable, or free forms of 25(OH)D, its active
metabolite
1,25(OH)2D,
Vitamin D Binding Protein (VDBP) concentrations, and relevant ratios are
associated with the risk for subsequent PE in women with T1DM. As
before, we include a group of healthy, normotensive non-diabetic
pregnant women to obtain normal reference values.