Maternal Serum Levels of 25-Hydroxy-Vitamin D During Pregnancy and Risk of Type 1 Diabetes in the Offspring

Ingvild M. Sørensen; Geir Joner; Pål A. Jenum; Anne Eskild; Peter A. Torjesen; Lars C. Stene


Diabetes. 2012;61(1):175-178. 

In This Article

Abstract and Introduction


Previous studies indicate reduced risk of type 1 diabetes after intake of vitamin D supplements during pregnancy or early childhood. We aimed to test whether lower maternal serum concentrations of 25-hydroxy-vitamin D (25-OH D) during pregnancy were associated with an increased risk of childhood-onset type 1 diabetes. In this case-control study nested within a cohort of 29,072 women in Norway, 25-OH D levels were measured using a radioimmunoassay on samples from late pregnancy in 109 women delivering a child who developed type 1 diabetes before 15 years of age (case subjects) and from 219 control women. Dividing the levels of maternal 25-OH D into quartiles, there was a trend toward a higher risk of type 1 diabetes with lower levels of vitamin D during pregnancy. The odds of type 1 diabetes was more than twofold higher for the offspring of women with the lowest levels of 25-OH D compared with the offspring of those with levels above the upper quartile. Given future replication in independent cohorts, our findings provide support for the initiation of a randomized intervention trial to prevent type 1 diabetes in children by enhancing maternal 25-OH D status during pregnancy.


Type 1 diabetes is an autoimmune disease that is one of the most common chronic diseases during childhood. With the exception of certain susceptibility genes, the causes of type 1 diabetes are essentially unknown. During recent years, there has been increasing interest in the immunomodulating actions of vitamin D in type 1 diabetes and other autoimmune diseases.[1,2]

The classical function of vitamin D is related to calcium and phosphate homeostasis and bone mineralization. Research over the last 30 years has revealed that vitamin D receptors are present in almost all body tissues, and there is increasing evidence that vitamin D is involved in a variety of processes in the body, including immunity.[3] Furthermore, immune cells, such as macrophages and dendritic cells as well as activated T cells and B cells, express the enzyme 1α-hydroxylase (CYP27B1), which is responsible for converting the major circulating metabolite of vitamin D, 25-hydroxy-vitamin D (25-OH D), to 1α,25-dihydroxyvitamin D [1,25-(OH)2D], the active form of vitamin D.[4] In autoimmune diseases, vitamin D is thought to have a protective effect, probably by enhancing immunologic tolerance.

Development of the immune system starts in early fetal life. Earlier studies in humans based on parental reports of vitamin D supplement use suggest that vitamin D supplementation during the 1st year of life may be associated with a reduced risk of type 1 diabetes.[5,6] Exogenous protective factors such as vitamin D may be of importance in utero. Some studies indicate an association between maternal intake of vitamin D during pregnancy and the development of diabetes-associated autoantibodies in the children.[7,8] On the other hand, a study from Finland[9] did not find such associations with either autoantibodies or overt diabetes in the offspring. We have previously found that the use of cod liver oil (which is an important source of vitamin D in Norway) during the 1st year of life,[10] and by the mother during pregnancy,[11] was less frequent in cases of childhood-onset type 1 diabetes than in control subjects. In addition to oral intake of vitamin D, the conversion of 7-dihydrocholesterol into vitamin D3 in the skin upon exposure to sunlight is an important source of vitamin D. The fact that the highest incidence of type 1 diabetes (with some exceptions) exists in the northern part of the world,[12] where sunshine hours are reduced for several months during the year, has been taken as support for the hypothesis that insufficient vitamin D status may increase the risk of type 1 diabetes.

Serum levels of 25-OH D are an accepted measure of the total vitamin D status, regardless of the source of vitamin D. In the current study, we tested whether lower maternal serum 25-OH D concentrations during late pregnancy were associated with an increased risk of childhood-onset type 1 diabetes in the offspring.


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