Summary: In this double-blind randomized controlled trial of 96 women with prediabetes, vitamin D 50,000 IU every two weeks for 12 weeks significantly raised insulin and HOMA-IR in both Omentin-1 Val109Asp genotypes, and a significant gene-by-treatment interaction was seen for HDL-C (p=0.003), which fell in AT carriers, waist circumference (p=0.026) and waist-to-height ratio (p=0.035). This is a hypothesis-generating pharmacogenetic signal, not evidence that vitamin D improves metabolism.
PICO Summary
| Element | Detail |
|---|---|
| Population | 204 women aged 18 to 65 with prediabetes genotyped for the Omentin-1 Val109Asp polymorphism; 96 randomized to study arms. Single-centre trial, Iran. |
| Intervention | Oral vitamin D 50,000 IU every two weeks for 12 weeks (n=48 across genotypes), double-blind. |
| Comparison | Matching placebo every two weeks for 12 weeks (n=48 across genotypes). |
| Outcome | Vitamin D significantly increased 25(OH)D, insulin, HOMA-IR, HOMA-β and QUICKI in both AT and TT genotypes (all p<0.001). HDL-C decreased significantly after vitamin D in the AT genotype but not the TT genotype (p<0.001). Significant vitamin D by Omentin-1 interaction on HDL-C (p=0.003), waist circumference (p=0.026) and waist-to-height ratio (p=0.035). No significant interaction on glycaemic factors, omentin-1 levels, other lipids or remaining anthropometric measures (p≥0.05). Effect sizes, 95% CIs and ARR/NNT were not reported in the abstract. |
Expert Commentary
This trial is best read as an exploratory pharmacogenetic analysis rather than a demonstration that vitamin D benefits prediabetic women. The headline result is an interaction: the Omentin-1 Val109Asp genotype appears to modify how vitamin D affects HDL-C and abdominal adiposity. The direction of effect is sobering. Far from improving glycaemic control, vitamin D was associated with significant rises in insulin and HOMA-IR in both genotypes, and HDL-C fell in AT carriers. These are not findings that support routine supplementation for metabolic benefit, and they sit against a wider literature in which high-dose vitamin D has repeatedly failed to prevent or improve type 2 diabetes. The principal limitation is statistical fragility: the genotype subgroups are very small, multiple metabolic outcomes were tested, and the report provides p-values without effect sizes or confidence intervals, so the interaction signals could reflect chance or multiplicity. The biological plausibility of a worsening insulin profile after vitamin D also warrants caution. Can I use this with my patients? Not yet. There is no actionable role for Omentin-1 genotyping or for vitamin D dosing to improve metabolism on the strength of this trial. I would reserve any change in practice until adequately powered trials report quantified, genotype-stratified effects with confidence intervals. For now, treat this as a hypothesis to test, not a result to apply.
References
Molani-Gol R, Rafraf M, Asghari Jafarabadi M, Aftabi-Yousefabad S, Shanehbandi D. The interaction of vitamin D supplementation with Omentin-1 gene polymorphism on metabolic biomarkers, omentin-1 levels and anthropometric measures in women with prediabetes: A double-blind randomized controlled trial. Diabetes Obes Metab. 2025;27(8):4522-4536. doi:10.1111/dom.16497