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.