Abstract
BACKGROUND: Prediabetes is a public health problem, and its prevalence is increasing around the world. Providing an effective strategy to prevent the progression of prediabetes and, consequently, type-2 diabetes mellitus (T2DM) could be useful for global health. Research suggests that vitamin D might contribute to decreasing the risk of developing and progressing T2DM. Moreover, Omentin-1 Val109Asp polymorphism is also reported to be associated with insulin resistance. Therefore, the primary aim of this trial is to investigate the interaction of vitamin D supplementation with Omentin-1 gene polymorphism on metabolic factors and anthropometric indices in women with prediabetes. METHODS/DESIGN: In this double-blind randomized controlled trial, prediabetic women (n = 204) aged 18–65 years that will be recognized based on FBS: 100–125 mg/dL or HbA1c: 5.7-6.4% will be invited to participate in this study. After obtaining informed consent, all participants’ blood samples will be achieved to determine the Omentin-1 polymorphism (Val109Asp) genotypes. Then the women will be randomized to the intervention (n = 24) or placebo (n = 24) groups (1:1) in each genotype of Omentin-1 polymorphism. In total, 144 women will be allocated to receive vitamin D (50000 IU) or a placebo (1:1) every two weeks for 12 weeks. Supplements will be provided to the participants at the beginning of the study and the end of each month and data will be collected at the baseline and after 12 weeks. Primary outcome measures are fasting glucose, insulin serum, and serum lipid profile levels, and secondary outcome measures include anthropometric parameters and dietary intakes. DISCUSSION: The present trial will provide more required clinical evidence on the effects of vitamin D supplementation on glycemic control and insulin resistance by considering Omentin-1 polymorphism genetic variation in prediabetic patients, which is relevant for preventing T2DM. TRIAL REGISTRATION: IRCT20100408003664N26. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-025-05034-2.