Vitamin D Deficiency Not Linked to Type 1 Diabetes, Study Finds

Despoina Manousaki, MD, PhD

A source of controversy in many disease states, new research suggests vitamin D levels do not impact the risk of type 1 diabetes in patients.

Despite previous studies suggesting vitamin D deficiency was linked to type 1 diabetes, results of the current study, which included nearly half a million patients, indicate genetically-determined vitamin D levels were unlikely to have a large effect on risk of type 1 diabetes.

"Our findings do not support a large effect of vitamin D levels on type 1 diabetes, but there may be smaller effects which we could not detect. Until further evidence from large RCTs, we cannot suggest the use of vitamin D supplements as a strategy to prevent type 1 diabetes in individuals at risk, for instance siblings or offspring of people with type 1 diabetes,” said Despoina Manousaki, MD, PhD, a pediatric endocrinologist and assistant professor the University of Montreal, in a statement.

In recent memory, few topics have received as much attention as the role of vitamin D levels in multiple diseases. With some observational studies suggesting low vitamin D levels were linked to risk of type 1 diabetes, investigators hoped to evaluate this association in a two-sample Mendelian randomization model.

For the purpose of analysis, investigators used single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels from a large genome-wide association study (GWAS) of 443,734 patients in Europe. Investigators used data from 12 different type 1 diabetes GWAS studies to obtain information related to 9358 cases of type 1 diabetes and 15,705 controls.

In their main analyses, investigators used inverse variance weighted Mendelian randomization and applied 3 additional methods to control for pleiotropy and compared the respective Mendelian randomization estimates. Additionally, investigators used sensitivity analyses excluding SNPs with potential pleiotropic effects. In total, investigators identified 69 lead independent common SNPs to be genome-wide significant for 25OHD, which explains 3.1% of the variance in 25OHD levels.

Upon analysis, results suggested that a 1 SD decrease in standardized natural log-transformed 25OHD was not associated with an increase in type 1 diabetes risk (IVW OR, 1.09; 95% CI, 0.86-1.40; P =.48). Investigators also observed similar results using 3 pleiotropy robust Mendelian randomization methods and in sensitivity analyses excluding SNPs associated with serum lipid levels, body composition, blood traits, and type 2 diabetes.

“Our results identified no large impact of a genetically determined reduction in 25OHD levels on type 1 diabetes risk. This provides critical insight into a complex disease that remains poorly understood. Our findings imply that the observational associations between 25OHD and risk of type 1 diabetes might be due to environmental confounders, such as latitude, which is correlated with exposure to sun and skin pigmentation, but this needs to be investigated in further studies,” wrote investigators.

This study, “Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study,” was published in PLOS Medicine.