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Type 1 Diabetes risk increased if high postpartum Vitamin D binding protein – Jan 2019

Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes.

Diabetes Care. 2019 Apr;42(4):553-559. doi: 10.2337/dc18-2176. Epub 2019 Jan 28.
Tapia G1, Mårild K2, Dahl SR3, Lund-Blix NA2,4,5, Viken MK6, Lie BA6,7, Njølstad PR8,9, Joner G5,10, Skrivarhaug T5,10, Cohen AS11, Størdal K2,12, Stene LC2.

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Table 2 Association between exposures and T1D

Image
P value shown for adjusted analysis. aOR, adjusted OR. *Adjusted for child’s HLA genotype, sex, maternal ethnicity, age, prepregnancy BMI, caesarean section, and smoking. †Using maternal (midpregnancy and postpartum) samples in a mixed model to predict maternal DBP values at gestational week 36. Owing to the reduction of the sampling variation in prediction of maternal DBP, the predicted values have a lower SD of 0.35 (while, e.g., DBP in the postpartum samples has an SD of 1.52). This results in a greater observed estimate, as an increase per unit is roughly equivalent to 3 SD in this analysis. We used bootstrapping (10,000 replications) to obtain unbiased CIs and present bias-corrected CIs. ‡As these results arise from bootstrapping estimations,a P value is not provided. §There was a statistically significant interaction (Pinteraction = 0.01) between rs11568820 and 25(OH)D (Supplementary Table 3).

OBJECTIVE:
Circumstantial evidence links 25-hydroxy vitamin D [25(OH)D], vitamin D-binding protein (DBP), vitamin D-associated genes, and type 1 diabetes (T1D), but no studies have jointly analyzed these. We aimed to investigate whether DBP levels during pregnancy or at birth were associated with offspring T1D and whether vitamin D pathway genetic variants modified associations between DBP, 25(OH)D, and T1D.

RESEARCH DESIGN AND METHODS:
From a cohort of >100,000 mother/child pairs, we analyzed 189 pairs where the child later developed T1D and 576 random control pairs. We measured 25(OH)D using liquid chromatography-tandem mass spectrometry, and DBP using polyclonal radioimmunoassay, in cord blood and maternal plasma samples collected at delivery and midpregnancy. We genotyped mother and child for variants in or near genes involved in vitamin D metabolism (GC, DHCR7, CYP2R1, CYP24A1, CYP27B1, and VDR). Logistic regression was used to estimate odds ratios (ORs) adjusted for potential confounders.

RESULTS:
Higher maternal DBP levels at delivery, but not in other samples, were associated with lower offspring T1D risk (OR 0.86 [95% CI 0.74-0.98] per μmol/L increase). Higher cord blood 25(OH)D levels were associated with lower T1D risk (OR = 0.87 [95% CI 0.77-0.98] per 10 nmol/L increase) in children carrying the VDR rs11568820 G/G genotype (P interaction = 0.01 between 25(OH)D level and rs11568820). We did not detect other gene-environment interactions.

CONCLUSIONS:
Higher maternal DBP level at delivery may decrease offspring T1D risk. Increased 25(OH)D levels at birth may decrease T1D risk, depending on VDR genotype. These findings should be replicated in other studies. Future studies of vitamin D and T1D should include VDR genotype and DBP levels.


Created by admin. Last Modification: Friday May 10, 2019 20:11:16 GMT-0000 by admin. (Version 5)

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11656 DBP postpartum.jpg admin 24 Mar, 2019 12:17 61.99 Kb 75
11655 10.2337@dc18-2176.pdf admin 24 Mar, 2019 12:17 790.44 Kb 37
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