Genetically increased circulating 25(OH)D level reduces the risk of type 2 diabetes in subjects with deficiency of vitamin D: A large-scale Mendelian randomization study
Medicine (Baltimore) . 2020 Dec 18;99(51):e23672. doi: 10.1097/MD.0000000000023672
Yingying Xu 1, Yuan Zhou 2, Jingjing Liu 1, Chenfang Wang 1, Zhongjie Qu 1, Zhili Wei 3, Dan Zhou 4
Items in both categories Diabetes and Genetics are listed here:
- DNA analysis of genes (Polygenic risk) shows increased risk of 9 health problems (all 9 fought by Vitamin D) – Feb 2024
- Increased Phosphorus increases Vitamin D getting to cells (CYP24A1, pigs) - Aug 2022
- Increased risk of diabetes if have poor Vitamin D genes – Dec 2020
- Poor CYP2R1 gene results in lower vitamin D and 2X increase in T1 Diabetes – Sept 2019
- Fasting and Diabetes both reduce Vitamin D activation (CYP2R1 in rodents) – May 2019
- Gestational Diabetes Mellitus associated with 4 Vitamin D genes – Oct 2015
- Diabetes changes liver genes so as to destroy (catabolize) Vitamin D – May 2016
- Low vitamin D in pregnancy – epigenetic pancreas problems in offspring (mice) – May 2016
- Diabetics with 8ng less vitamin D had a 50 percent increase chance of DHCR7 gene variation – Jan 2014
- Vitamin D receptor gene associated with 50 percent more type 2 Diabetes – meta-analyses 2013, 2016
- Fructose reduces blood levels of active vitamin D
- Type 1 diabetes, genes and vitamin D
- Vitamin D genes and insulin resistance – MS Aug 2010
Items in both categories Diabetes and Vitamin D Receptor are listed here:
- T2 Diabetes might be fought by Vitamin D plus Vitamin D Receptor activators – April 2023
- Diabetes 3X more likely if had COVID ICU (VDR was deactivated) - April 2023
- T2 diabetes complications increased 35-52 percent if low vitamin D – Sept 2022
- T2 Diabetes 30 percent more likely if poor Vitamin D Receptor – meta-analysis of 47 studies – July 2021
- Gestational Diabetes – increased risk if poor Vitamin D Receptor – 2 Meta-Analyses 2021
- Type 1 Diabetes (Autoimmune) and Vitamin D, Vitamin D Receptor and Cathelicidin - Dec 2020
- Diabetes decreased by activating Vitamin D Receptor (transgenic mice) – Feb 2020
- Gestational Diabetes 2.4X more likely if poor Vitamin D Receptor (region in China) – June 2019
- Gestational Diabetes 3 X more likely if poor Vitamin D receptor (Turkey) – May 2019
- Resveratrol prevented bone loss associated with T2DM (probably via VDR) – RCT Sept 2018
- Diabetic nephropathy deactivates the Vitamin D Receptor, reducing tissue Vit D – Feb 2019
- Resveratrol improves health (Vitamin D receptor, etc.) - many studies
- Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D) – July 2017
- Type 1 Diabetes 14 percent more likely with 2 Vitamin D Receptor mutations – Oct 2017
- Gestational Diabetes Mellitus associated with 4 Vitamin D genes – Oct 2015
- Diabetic nephropathy (Kidney problem) 1.8 X more likely if poor Vitamin D Receptor – meta-analysis July 2017
- Type 1 Diabetes association with poor Vitamin D Receptor: 39 studies – April 2017
- Type 1 diabetes 1.6 times more likely if a Vitamin D Receptor problem – Feb 2017
- Diabetic Retinopathy 2 X more likely if poor Vitamin D Receptor – meta-analysis Nov 2016
- Diabetic foot ulcer 1.7 times more likely if poor Vitamin D Receptor – Jan 2017
- Vitamin D activates the hypothalamus (in rodents) to reduce weight and diabetes– May 2016
- Diabetes (T2) 16 percent more likely if Vitamin D receptor problem – Oct 2015
- Type 1 diabetes associated with faulty Vitamin D receptor genes – May 2013
- Vitamin D receptor gene associated with 50 percent more type 2 Diabetes – meta-analyses 2013, 2016
Note: A poor Vitamin D Receptor reduces Vitamin D levels in the cells, not in the blood
Observational studies have reported that Vitamin D deficiency and the risk type 2 diabetes are associated, but the causation is unclear. Mendelian randomization (MR) involving genetic variants as instrument variables (IVs) overcomes the reverse-casualty and unmeasured confounding. However, with limited sample size and IVs, previous MR studies showed inconsistent results. Leveraging by a largely increased sample size for both stages, we aim to provide an updated and precise estimate for the causality between Vitamin D and type 2 diabetes.A 2-sample multi-IVs MR was performed. IVs for circulating 25-hydroxyvitamin D (25(OH)D) were obtained from a genome-wide association study from UK biobank involving 329,247 subjects of European ancestry. The causal effect of 25(OH)D and type 2 diabetes was estimated using traditional inverse variance weighting and MR pleiotropy residual sum and outlier (MR-PRESSO) framework which provides a robust estimate by systematically filtering out IVs identified with potential pleiotropy effects. A higher genetically instrumented 25(OH)D was causally linked to reduced risk of type 2 diabetes risk by MR-PRESSO [odds ratio (OR) per standard deviation (SD) = 0.950, 95% confidence interval (CI) = 0.913-0.988, P = .010] after removing 13 (13/193) invalid IVs. In addition, we confirmed the causal role Vitamin D using 2 synthesis-related single-nucleotide polymorphisms (SNPs) which are consistent with previous MR studies [OR per SD = 0.894, 95% CI = 0.816-0.979, P = .016].With a largely improved sample size, our results confirmed that genetically increased 25(OH)D concentration reduced the risk of type 2 diabetes and provided a more precise estimate for the effect size. The updated result empowers the role of Vitamin D and provides nontrivial evidence for interventional studies.