Plasma 25-hydroxyvitamin D concentration and risk of islet autoimmunity.

Nearly all immune cells express the vitamin D receptor, and vitamin D status may play a role in autoimmune disease. Studies examining the relationship between vitamin D status and islet autoimmunity (as well as its progression to type 1 diabetes), however, have produced discrepant results. In the Environmental Determinants of Diabetes in the Young (TEDDY) study, researchers examined whether 25(OH)D concentration in early infancy and throughout childhood was associated with the development of islet autoimmunity.

Methods

TEDDY is a prospective study of 8676 children at an increased risk of type 1 diabetes, based on HLA genotypes and family history. Newborn infants were evaluated every 3 months until age 4 and every 6 months after that for 25(OH)D concentration, serum autoantibodies to glutamate decarboxylase (GADA), insulinoma antigen-2 (IA-2A), and insulin (IAA). Persistent islet autoimmunity was defined as positive antibodies to the same antigen in 2 consecutive samples. Also, 9 polymorphisms in genes related to vitamin D metabolism (VDR, CYP24A, CYP27B1, GC, RXRA) were analyzed. 

The risk of type 1 diabetes appears to be lower in association with higher circulating 25(OH)D concentration.

Results

From 2004 to 2012, a total of 376 islet autoimmunity cases were identified and matched with 3 controls per case. Higher 25(OH)D was associated with a lower risk of islet autoimmunity (OR=0.93 for a 5nmol/L difference; 95% CI, 0.89-0.97). This association was observed in the entire cohort, but further analysis revealed that it was primarily seen in those carrying a specific variant of the VDR gene. In those with no minor alleles, there was no association between vitamin D status and islet autoimmunity, and the association became stronger with each additional minor allele at VDR rs7975232. 

Conclusions

The novel finding of this study is that the risk of islet autoimmunity and type 1 diabetes is lower in association with higher circulating 25(OH)D concentration and is also influenced by VDR genotype. The authors conclude that measuring vitamin D status as well as genetic variations in vitamin D metabolism genes may help identify children who would benefit most from intervention.

Norris, J.M., Lee, H.S., Frederiksen, B., Erlund, I., Uusitalo, U., Yang, J., …TEDDY Study Group. (2017). Plasma 25-hydroxyvitamin D concentration and risk of islet autoimmunity. Diabetes, 67(1):146-154.