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.