Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults

Abstract

BackgroundObservational 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. The aim of this study was to test the relevance of 25(OH)D for type 2 diabetes using genetically instrumented differences in plasma 25(OH)D concentrations.Methods and findingsData were available on four 25(OH)D single nucleotide polymorphisms (SNPs; n = 82,464), plasma 25(OH)D concentrations (n = 13,565), and cases with diabetes (n = 5,565) in the China Kadoorie Biobank (CKB). The effects on risk of diabetes were assessed by a genetic score using two 25(OH)D synthesis SNPs (DHCR7-rs12785878 and CYP2R1-rs10741657), with and without the addition of SNPs affecting the transport (GC/DBP-rs2282679) and catabolism (CYP24A1-rs6013897) of 25(OH)D. The CKB results were combined in a meta-analysis of 10 studies for the 2 synthesis SNPs (n = 58,312 cases) and 7 studies for all 4 SNPs (n = 32,796 cases). Mean (SD) 25(OH)D concentration was 62 (20) nmol/l in CKB, and the per allele effects of genetic scores on 25(OH)D were 2.87 (SE 0.39) for the synthesis SNPs and 3.54 (SE 0.32) for all SNPs. A 25-nmol/l higher biochemically measured 25(OH)D was associated with a 9% (95% CI: 0%–18%) lower risk of diabetes in CKB. In a meta-analysis of all studies, a 25-nmol/l higher genetically instrumented 25(OH)D concentration was associated with a 14% (95% CI: 3%–23%) lower risk of diabetes (p = 0.01) using the 2 synthesis SNPs. An equivalent difference in 25(OH)D using a genetic score with 4 SNPs was not significantly associated with diabetes (odds ratio 8%, 95% CI: −1% to 16%, lower risk, p = 0.07), but had some evidence of pleiotropy. A limitation of the meta-analysis was the access only to study level rather than individual level data.ConclusionsThe 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.

Vitamin D Supplementation and Prevention of Type 2 Diabetes

“…Over the past decade, a low blood 25-hydroxyvitamin D level has emerged as a possible risk factor for type 2 diabetes, and vitamin D supplementation has been proposed as a potential intervention to lower diabetes risk. 3,4 The hypothesis that vitamin D status may influence the risk of type 2 diabetes is biologically plausible, because both impaired pancreatic beta-cell function and insulin resistance have been reported with low blood 25-hydroxyvitamin D levels. 5 Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of diabetes.…”

Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D?

“…Over the last decade, low blood 25-hydroxyvitamin D (25[OH]D) level has emerged as a risk factor for type 2 diabetes, and vitamin D supplementation has been hypothesized as a potential intervention to lower diabetes risk ( 6 , 7 ). Observational studies strongly support an inverse association between blood 25(OH)D level and risk of developing type 2 diabetes in diverse cohorts of variable diabetes risk, especially in persons with prediabetes ( 8 , 9 ).…”

Diabetic Retinopathy: Changes in Levels of Orosomucoids in Patients Supplemented with Beta Glucan and Vitamin D

“…Attempts to increase the interests of general public in consumption of food with higher content of vitamin D (either naturally or as a supplement) is increasing (Spiro and Buttriss, 2014;Tessari and Lante, 2017;Aoe et al, 2017). Lately, an association between vitamin D deficit and risk of DM2 development is being discussed in the literature (Lu et al, 2018). Our findings show that vitamin D supplementation helps to improve several clinical manifestation of DM2 and its complications (Zavorkova et al, 2018;Christiansen et al, 2010).…”

“…Effects of glucan in prevention and treatment of obesity and clinical manifestation of DM2 were tested both in experimental and clinical studies (Hajer et al, 2008;Richter et al, 2018a;2018b;Lu et al, 2018). Clinical trials confirmed that glucan supplementation resulted in a decrease of glycemic index and lipid metabolism, particularly cholesterol levels (Lu et al, 2018;Sima et al, 2018). Findings of changes in visceral obesity after glucan treatment, accompanied with decrease of weight and BMI are important (Wang et al, 2016).…”

“…Several studies demonstrated associations between levels of vitamin D and incerased risk of development of DM2 (Lu et al, 2018;Spiro and Buttriss, 2014). Vitamin D supplementation, resulting in changes of its levels, results in significant decrease of risk of DM2 (Zavorkova et al, 2018;Luo et al, 2015).…”