Genetically reduced vitamin D levels do not appear to significantly affect the risk of type 1 diabetes (T1D) among European populations, according to the results of a published Mendelian randomized control (MR) study in Medicine PLOS.
Although several observational studies have suggested an association between T1D and serum 25 hydroxyvitamin D (25OHD) deficiency, there is a lack of evidence from large randomized controlled trials (RCTs). Moreover, speculative studies “tend to cause confusion and backlash, so it is not clear whether these associations are correct,” the authors wrote.
Currently, there are no known treatments that can be used to prevent T1D, while the prevalence under the age of 14 is expected to rise 3% per year worldwide. In addition, “the incidence of vitamin D incompatibility is estimated to be 43% in the general population and is also increasing,” said researchers.
To better understand the causal link between vitamin D and T1D, researchers conducted a 2-sample MR study using single nucleotide polymorphisms (SNPs) from the largest genome-wide association (GWAS) study of vitamin D to seo (n = 443,734).
“To satisfy the initial MR assumption, which requires the instrument (SNP) to be strongly linked to the publication (25OHD rating), we selected as SNP instruments associated with 25OHD ratings at a level of 25OHD. genome-wide importance. (P. <6.6 × 10−9), ”said authors.
Researchers then extracted estimates of the effect of 23OHD-related changes on T1D from a GWAS meta-analysis of 12 European studies, which included 9358 cases and 15,705 controls.
69 leads of common independent SNPs, which make up 3.1% of the variance in vitamin D levels, were used as instruments in the studies. However, 8 were absent in the GW1 T1D and so substitutes were substituted in high-binding disequilibrium (LD) (r2> 0.7). Specifically, a study of 25,063 people “had 80% power to inhibit effects on T1D as little as an OR of 1.23 per 1 SD change in 25OHD on the scale of logs and 100% power to effect effects as small as NO of 1.4). ”
Studies have shown that:
- There was no evidence to support a causal link between 25OHD levels and T1D risk (unchanged weight [IVW] MR OR, 1.09; 95% CI, 0.86–1.40; P. = 0.48 per 1 SD reduction in normal log transmitted 25OHD)
- SD change in normal 25OHD levels transformed by natural log was thought to correspond to change in 25OHD levels of 40.9 nmol / l in individuals with vitamin D (defined as 25OHD levels of 70. nmol / l), of 29.2 nmol / l in individuals with vitamin D (25OHD levels of 50 nmol / l), and of 14.6 nmol / l in individuals with vitamin D (25OHD levels of 25 nmol / l )
- Enrichment in SNPs was associated with specific trait regions (among 1641 SNP-trait associations with 494 individual markers detected, 246 links with blood cell count were observed, 250 links with body shape markers, and 213 links le serum lipids)
Similar results were found when researchers used 3 strong MR pleiotropy methods (MR-Egger, mean weight, and method-based estimation) and performed sensitivity analyzes without SNPs related to serum lipid levels, body composition, blood symptoms, and type 2 diabetes.
Levels of vitamin D levels compared with normal dose effects of vitamin D fortification in deficient individuals.
“Our conclusions with confidence exclude significant effects (OR> 1.40), given the sufficient statistical power and the consistency of the estimates using different MR methods and in the sensitivity analyzes,” he wrote. authors. “However, the relatively high confidence times of an MR result indicate that minor effects cannot be ruled out, and further evidence is needed to investigate such effects. ”
Researchers acknowledge that pre-existing associations may have been the result of complex factors including latitude and exposure to sunlight. Since it is not known for certain what exactly the majority of SNPs included in the study are, it is possible that residual bias is indicated, indicating a limitation. It may not be possible to give general results to numbers living outside the continent of Europe.
“Until further evidence comes from major RCTs, we cannot recommend the use of vitamin D products as a strategy to prevent T1D in at-risk individuals, for example sisters or children of people with T1D. , ”Said the lead author of the study Despoina Manousaki, MD.
Information
Manousaki D, Harroud A, Mitchell RE, et al. Vitamin D levels and risk of type 1 diabetes: a randomized Mendelian study. PloS Med. Published online February 25, 2021. doi: 10.1371 / journal. pmed.1003536