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Type 2 Diabetes Causally Reduces Circulating Vitamin D Levels: A Multi-Ancestry Mendelian Randomization Study
Madhusmita Rout1, Piers Blackett1,2,3, Dharambir K Sanghera1,4,5,6,7,8
1Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Nutrients
|June 26, 2026
Summary
Low vitamin D levels do not appear to cause type 2 diabetes (T2D) or cardiovascular disease. Instead, genetic risk for T2D may lead to vitamin D deficiency, highlighting its role in secondary prevention.
Area of Science:
- Endocrinology
- Genetics
- Cardiovascular Disease Epidemiology
Background:
- Vitamin D deficiency is a global health issue linked to type 2 diabetes (T2D) and cardiometabolic diseases.
- Previous vitamin D supplementation trials showed limited T2D risk reduction, questioning its causal role.
- Genetic insights into vitamin D levels exist, but their predictive value for cardiometabolic outcomes is uncertain.
Purpose of the Study:
- To investigate the causal relationship between vitamin D status and T2D risk using genetic data.
- To explore whether genetically determined vitamin D levels influence cardiometabolic disease risk.
- To examine the reverse association: whether T2D genetic susceptibility impacts vitamin D levels.
Main Methods:
- Utilized large, multi-ethnic cohorts (UK Biobank, Asian Indian Diabetic Heart Study).
- Employed genome-wide univariate and polygenic risk score (PRS)-based bidirectional Mendelian randomization (MR) analyses.
- Assessed associations between vitamin D-raising alleles PRS, T2D PRS, and circulating 25(OH)D levels.
Main Results:
- A polygenic score for vitamin D-raising alleles did not alter T2D or cardiovascular disease risk.
- Higher T2D PRS was significantly associated with increased risk of 25(OH)D deficiency.
- Increased T2D genetic risk predicted a significant decrease in circulating 25(OH)D levels across all ancestries.
Conclusions:
- Low circulating vitamin D is unlikely a causal predictor of T2D risk but may indicate secondary prevention needs.
- Genetic susceptibility to T2D appears to drive vitamin D insufficiency, potentially contributing to cardiovascular complications.
- Further research is required to elucidate the mechanisms of vitamin D deficiency in diabetes.
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