Type 1 diabetes risk unaffected by vitamin D levels: Study
Canada: Vitamin D levels are not likely to have large effect on type 1 diabetes risk (T1D), suggests a recent study in the journal PLOS Medicine. However, the researchers added that larger MR studies or RCTs are required to investigate small effects.
"Our findings suggest that vitamin D levels are unlikely to have a large effect on risk of type 1 diabetes," wrote the authors.
In observational studies, vitamin D deficiency is shown to be associated with T1D but there is a lack of evidence from randomized controlled trials (RCTs). Despoina Manousaki, Research Center of the Sainte-Justine University Hospital, Montreal, Quebec, Canada, and colleagues aimed to test whether genetically decreased vitamin D levels are causally associated with type 1 diabetes using Mendelian randomization (MR).
For the two-sample MR study, the researchers selected as instruments single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels in a large vitamin D genome-wide association study (GWAS). It included 443,734 Europeans and obtained their corresponding effect estimates on type 1 diabetes risk from a large meta-analysis of 12 type 1 diabetes GWAS studies (Ntot = 24,063, 9,358 cases, and 15,705 controls).
Using inverse variance weighted MR, 3 additional method methods were applied to control for pleiotropy (MR-Egger, weighted median, and mode-based estimate) and compared the respective MR estimates. Sensitivity analyses was also undertaken excluding SNPs with potential pleiotropic effects.
Key findings of the study include:
- The researchers identified 69 lead independent common SNPs to be genome-wide significant for 25OHD, explaining 3.1% of the variance in 25OHD levels.
- MR analyses suggested that a 1 standard deviation (SD) decrease in standardized natural log-transformed 25OHD (corresponding to a 29-nmol/l change in 25OHD levels in vitamin D–insufficient individuals) was not associated with an increase in type 1 diabetes risk (inverse-variance weighted (IVW) MR odds ratio (OR) = 1.09).
- Similar results were obtained using the 3 pleiotropy robust MR methods and in sensitivity analyses excluding SNPs associated with serum lipid levels, body composition, blood traits, and type 2 diabetes.
"Our findings indicate that decreased vitamin D levels did not have a substantial impact on risk of type 1 diabetes in the populations studied," concluded the authors. "Study limitations include an inability to exclude the existence of smaller associations and a lack of evidence from non-European populations."
The study titled, "Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study," is published in the journal PLOS Medicine.
DOI: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003536
