Elsevier

The Journal of Pediatrics

Volume 212, September 2019, Pages 28-34.e2
The Journal of Pediatrics

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

https://doi.org/10.1016/j.jpeds.2019.04.057Get rights and content

Objective

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.

Study design

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.

Results

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.

Conclusions

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.

Section snippets

Methods

Seventy-nine adolescents were evaluated in this cross-sectional study. Glucose tolerance status was defined according to American Diabetes Association criteria after a 2-hour oral glucose tolerance test (OGTT).12 Normal glucose tolerance was thus defined as glycosylated hemoglobin (HbA1c) <5.7%, fasting glucose <100 mg/dL, and a 2-hour value less than 140 mg/dL during the OGTT; impaired fasting glucose (IFG) as a fasting glucose ≥100 mg/dL, impaired glucose tolerance (IGT) as a 2-hour value

Results

Seventy-nine pubertal youth (34 male and 45 female; 42 Hispanic, 23 black, and 14 white), 15.4 ± 0.2 years in age, underwent study evaluations. Subjects' characteristics are detailed in Table I. Of the 79 subjects, only 17 met the criteria for vitamin D sufficiency, using a cut-off of 20 ng/mL. To evaluate the effect of free 25(OH)D or BioD on outcomes of interest, the subjects were examined according to tertiles of free 25(OH)D (Table I), or tertiles of BioD concentrations (Table II; available

Discussion

Our findings of endothelial dysfunction as measured by RHI in the lowest tertiles of free 25(OH)D and in association with total 25(OH)D deficiency vs sufficiency are consistent with findings of a relationship of low vitamin D concentrations with measures of vascular stiffness,5 intima media thickness,6 and markers of inflammation4 in youth. This is also consistent with adult studies suggesting that vitamin D plays an important role in cardiovascular health and is an independent risk factor for

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    Supported by the USDA ARS 6250-5100-054 (to F.B.) and Thrasher Research Fund (to F.B.). The authors declare no conflicts of interest. Portions of this study were presented at the Obesity Society Meeting, November 2015, Los Angeles, CA

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