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Vitamin D and Type 2 Diabetes Risk

In an analysis using genetic data from over 25 different studies involving diabetes patients, researchers can find no causal association between higher vitamin D levels and lower diabetes risk…
Low circulating concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, have been associated with an increased risk of type 2 diabetes, but whether this association is causal remains unclear. In a new study, researchers attempted to estimate the unconfounded, causal association between 25(OH)D concentration and risk of type 2 diabetes using a mendelian randomization approach.
Using several data sources from populations of European descent, including type 2 diabetes cases and non-cases, they performed a mendelian randomization analysis using single nucleotide polymorphisms (SNPs) within or near four genes related to 25(OH)D synthesis and metabolism: DHCR7 (related to vitamin D synthesis), CYP2R1 (hepatic 25-hydroxylation), DBP (also known as GC; transport), and CYP24A1 (catabolism). They assessed each SNP for an association with circulating 25(OH)D concentration (5,449 non-cases; two studies), risk of type 2 diabetes (28,144 cases, 76,344 non-cases; five studies), and glycemic traits (concentrations of fasting glucose, 2-h glucose, fasting insulin, and HbA1c; 46,368 non-cases; study consortium). They combined these associations in a likelihood-based mendelian randomization analysis to estimate the causal association of 25(OH)D concentration with type 2 diabetes and the glycemic traits, and compared them with that from a meta-analysis of data from observational studies (8,492 cases, 89,698 non-cases; 22 studies) that assessed the association between 25(OH)D concentration and type 2 diabetes.
All four SNPs were associated with 25(OH)D concentrations (p<10−6). The mendelian randomization-derived unconfounded odds ratio for type 2 diabetes was 0.93 (95% CI 0.77-1.13; p=0.46) per 25.0 nmol/L (1 SD) lower 25(OH)D concentration. The corresponding (potentially confounded) relative risk from the meta-analysis of data from observational studies was 1.22 (1.16-1.29; p=3.5 × 10−14). The mendelian randomization-derived estimates for glycemic traits were not significant (p>0.25).
Practice Pearls:
  • The association between 25(OH)D concentration and type 2 diabetes is unlikely to be causal.
  • Efforts to increase 25(OH)D concentrations might not reduce the risk of type 2 diabetes as would be expected on the basis of observational evidence.
  • These findings warrant further investigations to identify causal factors that might increase 25(OH)D concentration and also reduce the risk of type 2 diabetes.
The Lancet Diabetes & Endocrinology, early online publication, 1 October 2014, Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study. doi:10.1016/S2213-8587(14)70184-6.