Free Vitamin D: Relationship to Insulin Sensitivity and Vascular Health in Youth

To evaluate the relationship of free 25 hydroxy vitamin D [free 25(OH)D] or bioavailable vitamin D (BioD) concentrations to insulin sensitivity and cardiovascular disease risk markers in normal weight and overweight youth.

Cross-sectional study of 79 adolescents 15.4 ± 0.2 years, 18 normal weight, 30 overweight, and 31 overweight with prediabetes who underwent peripheral arterial tonometry, dual-energy x-ray absorptiometry, and hyperinsulinemic-euglycemic clamp in subset (n = 71) for determination of reactive hyperemia index (RHI), body composition, and insulin sensitivity. 25(OH)D and vitamin D binding protein were measured; free 25(OH)D and BioD were calculated.

Across tertiles of free 25(OH)D concentrations (4.0 ± 0.2, 7.5 ± 0.3, and 17.0 ± 2.1 pg/mL, P < .001), the group in the lowest tertile had significantly higher percent body fat (37.8 ± 1.1, 35.2 ± 1.5 and 25.3 ± 2.1%, P < .001), lower insulin sensitivity (4.4 ± 0.4, 6.7 ± 1.2, and 8.2 ± 0.9 mg/kg fat-free mass/minute per μu/mL, P = .03), lower RHI (1.42 ± 0.06, 1.54 ± 0.06, and 1.77 ± 0.09, P = .002), higher high-sensitivity C-reactive protein (3.4 ± 0.6, 1.7 ± 0.3, and 1.6 ± 0.4 mg/L, P = .015) compared with the second and third tertiles, respectively. Free 25(OH)D levels were inversely related to percent body fat and high-sensitivity C-reactive protein, and positively related to RHI and insulin sensitivity. The relationships of free 25(OH)D to RHI and to insulin sensitivity were no longer significant after adjusting for %body fat. Similar relationships were observed for BioD.

Youth with low free 25(OH)D or BioD concentrations have lower insulin sensitivity and worse endothelial function and inflammatory biomarkers compared with those with more sufficient 25(OH)D. However, the effects of vitamin D on these biomarkers may not be independent of the effect of adiposity.