Characteristics of the study population are shown in Table 1. The mean age at diabetes diagnosis in the children was 9.0 years (SD 3.6). No significant differences were observed between case and control subjects regarding age and parity of the women, gestational week of the blood sample, frequency of caesarean section, or maternal diabetes before pregnancy. Unexpectedly, there were significantly more girls among the case children than in the control subjects.
The mean serum levels of 25-OH D were significantly lower in case subjects than in control subjects (65.8 vs. 73.1 nmol/L) (Table 2), and there was an expected seasonal variation in 25-OH D levels (Fig. 1). The relationship between the serum levels of 25-OH D during pregnancy and the risk of childhood-onset type 1 diabetes in offspring is presented in Table 2. The odds of type 1 diabetes was more than twofold higher for children born from women with a 25-OH D level in the first quartile compared with women with a 25-OH D level in the fourth quartile, and the linear trend was significant, even after adjustment for sex and season of blood draw (Table 2). Additional adjustments were done for all variables in Table 1, and the results remained similar and significant (OR for the first vs. fourth quartile 2.39 [95% CI 1.07–5.31]; P (trend) = 0.032, data not shown). Figure 2 shows the distribution of maternal 25-OH D during pregnancy in case mothers and in control mothers. The two subjects with the highest 25-OH D values were case subjects. This resulted in a suggested upward trend in risk at the highest values of 25-OH D, but this should be interpreted with caution because of few observations and wide CIs (Supplementary Fig. 1). We further formally compared the model in which 25-OH D was modeled linearly to models with a square and a cubic term and found that the polynomial regression models did not provide any significantly better fit than the linear one (P ≥ 0.23, likelihood ratio tests).
Smoothed average serum levels of 25-OH D versus season of blood collection in pregnant women whose child later developed type 1 diabetes (case subjects, solid line) and control subjects (dotted line). Smoothing was conducted using kernel-weighted local polynomial regression in Stata version 11.
Distribution of maternal 25-OH D during pregnancy in case mothers whose child later developed type 1 diabetes and in control mothers. Two case subjects and one control subject had a 25-OH D value >150 nmol/L.
Diabetes. 2012;61(1):175-178. © 2012 American Diabetes Association, Inc.