Image: The Access 2 benchtop immunoassay system (Photo courtesy of Beckman Coulter Diagnostics).
The incidence of type 2 diabetes has increased substantially in both high-income and low- and middle-income countries in recent decades. Observational studies have reported that higher plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with lower risks of diabetes, but it is unclear if these associations are causal.
Vitamin D insufficiency, defined as plasma 25-hydroxyvitamin D (25[OH]D) concentration of less than 75 nmol/L, is common in European and Asian populations, particularly among those living at high latitude, during the winter months, or among those in cities with poor air quality. Mendelian randomization (MR) studies of genetic variants can help to assess the causal relevance of vitamin D status for risk of diabetes.
Scientists from Oxford University (Oxford, UK) and their Chines colleagues tested the relevance of 25(OH)D for type 2 diabetes using genetically instrumented differences in plasma 25(OH)D concentrations. Blood samples were taken from 13,565 participants and 5,565 cases with diabetes. After centrifugation of thawed stored EDTA plasma samples, plasma 25(OH)D concentration was measured using a Beckman Coulter Access 2 immunoassay system in 13,565 participants, of whom 3,014 also participated in the genetic study.
A total of 95,680 randomly selected participants were genotyped using a panel of 384 single nucleotide polymorphisms (SNPs). The genotyping panel included two synthesis SNPs (DHCR7-rs12785878 and CYP2R1-rs10741657), one transport SNP (GC/DBP-rs2282679), and one catabolism SNP (CYP24A1-rs6013897), identified as significantly associated with plasma 25(OH)D concentration in previous genome-wide studies.
Among the 82,464 participants in the genetic study, the mean (SD) age was 51.4 ± 10.6 years, 61% were women. The overall mean plasma 25(OH)D concentration was 62.1± 20 nmol/L, consistent with values previously reported in Chinese and in European populations. Mean plasma concentration of 25(OH)D was lower in participants recruited in winter than in summer, 57.4 versus 68.4 nmol/L, respectively, but was unrelated to age, sex, physical activity, or percent body fat.
The MR study of genetic variants influencing the synthesis of plasma 25(OH)D concentration, involving over 58,000 cases and 370,000 controls, demonstrated concordant risks of diabetes for genetically instrumented differences in 25(OH)D using synthesis SNPs and biochemically measured differences, and provides novel evidence for a causal protective effect of higher 25(OH)D concentrations on the risk of diabetes. The authors concluded that the concordant risks of diabetes for biochemically measured and genetically instrumented differences in 25(OH)D using synthesis SNPs provide evidence for a causal effect of higher 25(OH)D for prevention of diabetes. The study was published on May 2, 2018, in the journal Public Library of Science Medicine.