Vitamin D Metabolite Ratios and Association with Type 2 Diabetes Mellitus in a Youth Saudi Population

Purpose: Vitamin D deficiency is highly prevalent in Saudi Arabia and has been associated with type 2 diabetes mellitus (T2DM). The vitamin D metabolite ratio (VMR), defined as the ratio of 24,25-dihydroxyvitamin D 3 [24,25(OH) 2 D 3 ] to 25-hydroxyvitamin D 3 [25(OH)D 3 ], may provide a more functional assessment of vitamin D status than total 25(OH)D alone. This study aimed to investigate the associations between vitamin D metabolite ratio and T2DM status in a Saudi youth cohort. Patients and Methods: A cross-sectional study was conducted involving 971 Saudi adolescents (age 14.9 ± 1.7 years), including 864 normoglycemic individuals, 74 with prediabetes, and 33 with T2DM. Serum vitamin D metabolites [25(OH)D 3 , 24,25(OH) 2 D 3 , and 25(OH)D 2 ] were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The vitamin D metabolite ratio was calculated, and its association with T2DM was assessed using logistic regression analysis adjusted for age and body mass index (BMI). VMR was analyzed both as a continuous variable and dichotomized at < 4% versus ≥ 4%. The 4% threshold was selected based on preliminary data from adult populations and exploratory analysis of our data distribution, recognizing that this threshold requires validation in adolescent cohorts. Results: Lower VMR (< 4%) was associated with higher odds of T2DM (OR: 4.7, 95% CI: 1.1– 20.0, p = 0.036), though the wide confidence interval reflects the small T2DM sample size (n=33). Preliminary analysis indicated that VMR may be associated with T2DM in Saudi adolescents, but findings should be interpreted cautiously given the small T2DM sample and cross-sectional design. Larger prospective studies are needed to confirm these preliminary observations. Conclusion: A lower vitamin D metabolite ratio is associated with T2DM among Saudi adolescents. VMR may provide complementary information beyond total 25(OH)D; however, formal comparative predictive analyses were not performed, underscoring the importance of proper vitamin D metabolism in glucose homeostasis. However, given the cross-sectional design and small T2DM sample size, these findings are preliminary and require validation in larger prospective studies.