Results
Maternal characteristics: Table 1 shows the baseline clinical
characteristics of all women. There were no significant differences in
age, ethnicity, smoking, gravidity, parity, duration of T1DM, systolic
and diastolic blood pressure, mean arterial pressure (MAP), total
cholesterol, LDL-cholesterol, triacylglycerol, and gestational age per
visit between DM+PE+ and DM+PE-. However, at the initial study visit,
HbA1c, Body Mass Index (BMI) and total daily insulin dose were
significantly higher in DM+PE+
than DM+PE-, and HDL-cholesterol was significantly lower. There were no
significant differences between the two normotensive groups at V1,
except as expected, HbA1c was higher in women with diabetes.
25(OH)D deficiency was not associated with subsequent PE in women
with T1DM: Vitamin D insufficiency and deficiency are defined as
<32 and <20 ng/mL, respectively.6As shown in Figure 1, a majority (97%) of all women fell below the
‘normal’ level of vitamin D throughout pregnancy. Women with T1DM were
more likely to be 25(OH)D deficient (DM+PE+: 73%; DM+PE-: 65%) than
non-diabetic women (22%) at the first visit (p=0.009); however there
were no significant differences in any measure of 25(OH)D during
pregnancy between the DM+PE+ and DM+PE- groups. Total 25(OH)D was lower
in DM+PE- than in DM- groups at the beginning of pregnancy (V1, p=0.020;
V2, p=0.034), but neither bioavailable nor free 25(OH)D differed by
diabetes status at any visit.
Higher second and/or third trimester 1,25(OH)2D
(total, bioavailable, free) are associated with subsequent PE in women
with T1DM: As shown in Figure 2, in the DM+PE+ vs the DM+PE- group,
total 1,25(OH)2D
was higher at V2 (p=0.005), and bioavailable and free
1,25(OH)2D were higher at V2 and V3 (bioavailable: V2,
p=0.005; V3, p=0.031; free: V2, p=0.007 & V3, p=0.009). In the DM+PE-
vs. the DM- group, all measures of 1,25(OH)2D were lower
at V2 (total, p=0.002; bioavailable, p=0.004; free, p=0.018). Total
1,25(OH)2D significantly increased as pregnancy advanced
in DM+PE+ (p<0.001) and DM+PE- (p=0.007).
Using logistic regression, data were analysed without and with
covariates to assess the effectiveness of 1,25(OH)2D as
a biomarker of PE. At V2, without covariates and in women with T1DM
only, every 1 pg/mL increase in total 1,25(OH)2D
increased the odds of developing PE by 3% (OR: 1.03 (1.01-1.05),
p=0.012), while every 1pg/mL
increase in bioavailable 1,25(OH)2D increased the odds
for PE by 28% (OR: 1.28 (1.06-1.54), p=0.010). Likewise, at V3, every 1
pg/mL increase in bioavailable 1,25(OH)2D increased the
odds for PE by 18% (OR: 1.18 (1.00-1.39), p=0.047). Covariate analyses
including BMI, HbA1c and total adiponectin did not affect significance.
Ratios of total, bioavailable, and free 1,25(OH)2D
to corresponding 25(OH)D concentrations (Table 2): In the DM+PE+ vs the
DM+PE- group, total, bioavailable and free
1,25(OH)2D/25(OH)D (product:substrate) ratios were all
higher at V3 (all p<0.05). There were no significant
differences in these ratios at any stage of pregnancy between the DM+PE-
and DM- groups, and there were no significant changes over time in any
of the groups. For women with T1DM only, at V3, for every unit increase
in total 1,25(OH)2D/25(OH)D, the odds of developing PE
increased by 17% (OR: 1.17 (1.01-1.35), p=0.037), however, this
significance did not persist after covariate adjustment.
Lower VDBP and higher 1,25(OH)2D/VDBP ratio are
associated with subsequent PE in women with T1DM: As summarized in
Table 2, in the DM+PE+ vs the DM+PE- group, VDBP was lower at V3
(p=0.032), and total 1,25(OH)2D/VDBP and
[1,25(OH)2D bound to VDBP]/VDBP were both higher at
V2 & V3 (all p<0.01). Total 25(OH)D/VDBP and [‘25(OH)D
bound to VDBP’]/VDBP did not differ between DM+PE+ and DM+PE- at any
study visit. In the DM+PE- vs the DM- group, total
1,25(OH)2D/VDBP and
[‘1,25(OH)2D
bound to VDBP’]/VDBP were lower at V2 (p=0.025 and p=0.018
respectively). VDBP significantly increased throughout pregnancy in all
groups (all p<0.001). For women with T1DM only, for every 1
mg/dL increase in VDBP at V3, the odds of developing PE decreased by 8%
(OR: 0.92 (0.85-1.00), p<0.05). At V2, for every unit increase
in total 1,25(OH)2D/VDBP, the odds of developing PE
increased almost three-fold (OR: 2.71 (1.28-5.77), p=0.009). Likewise,
at V3, for every unit increase in total 1,25(OH)2D/VDBP,
the odds of developing PE increased similarly (OR: 2.53 (1.21-5.29),
p=0.013). Consideration of covariates had no effect.