Highlights From the Latest in Diabetes Research

Multiple investigations have evaluated the relationship between obesity and vitamin D defi ciency, two modifi able factors that contribute to the risk of several chronic diseases. While such studies have identifi ed a strong association between these phenotypes, it has been diffi cult to determine causality and the direction of the association. Through a series of sophisticated genetic analyses including bi-directional Mendelian randomization (MR), results from Vimaleswaran et al. have highlighted potentially important insights regarding the link between obesity, as assessed by BMI, and vitamin D defi ciency. Using meta-analysis approaches in approximately 42,000 participants of D-CarDia, the authors observed that each unit increase in BMI was associated with a 1.15% decrease in 25-hydroxyvitamin D [25(OH)D]. In order to infer causality, their fi ndings were extended by MR using previously established BMI-related (n = 12) and vitamin D–related (n = 4) single nucleotide polymorphisms in order to generate allele scores for the analyses. These analyses revealed that while the BMI allele score was signifi cantly associated with reduced 25(OH)D levels (-0.06% [95% CI -0.10 to -0.02%], P = 0.004), neither the vitamin D synthesis or metabolism allele scores were associated with BMI (0.01 [-0.17 to 0.20], P = 0.88 and 0.17 [-0.02 to 0.35], P = 0.08, respectively). Using the instrumental variable (IV) ratio method, it was observed that each 10% increase in BMI led to a 4.2% decrease in 25(OH)D levels. In contrast, IV analyses did not provide evidence that 25(OH)D levels signifi cantly affected BMI. Follow-up analyses using data from the Genetic Investigation of Anthropometric Traits (GIANT) consortium confi rmed the lack of association between vitamin D allele scores and BMI. Together, these results suggest that an increase in obesity results in lower vitamin D status but that vitamin D concentration has little or no impact on the development of obesity. — Joshua P. Lewis, PhD