Effect of vitamin D supplementation on microvascular reactivity in obese adolescents: A randomized controlled trial.

BACKGROUND AND AIM: Childhood obesity is associated with vitamin D (VD) deficiency and vascular dysfunction. Considering evidence indicates that VD may improve vascular function, this study, for the first time, assessed the effect of VD supplementation on microvascular reactivity in obese adolescents (OA). METHODS AND RESULTS: This randomized controlled trial included 26 OA, receiving fruit juice with (n = 13) or without VD (4000 IU/d; n = 13) over a 3-month lifestyle program, as well as 23 normal-weight adolescents (controls). The primary outcome was the pre-to-post-program change in microvascular reactivity determined by laser speckle contrast imaging with acetylcholine and sodium nitroprusside iontophoresis. Changes in 25 hydroxyvitamin D (25(OH)D), flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), insulin resistance (HOMA-IR) and inflammatory markers (C-reactive protein [CRP]) were monitored. At inclusion, in comparison to controls, OA exhibited lower total and free 25(OH)D, impaired microvascular responses, and impaired FMD, but similar NMD. After the lifestyle program, total and free 25(OH)D increased in all OA, with a greater increase in those receiving VD supplements. HOMA-IR and CRP decreased in all OA. Neither FMD nor NMD were altered in either group. Endothelium-dependent microvascular reactivity only increased in the VD-supplemented group, reaching values comparable to that of controls. Similar results were found when analyzing only OA with a VD deficiency at baseline. CONCLUSION: VD supplementation during a lifestyle program attenuated microvascular dysfunction in OA without altering macrovascular function. REGISTRATION NUMBER FOR CLINICAL TRIAL: NCT02400151.

Effects of Exercise Intensity on Microvascular Function in Obese Adolescents.

The optimal exercise modality for the improvement of health-related parameters and microvascular function in obese adolescents is not yet fully understood. Therefore, this study aimed to 1) compare the microvascular phenotype of obese and normal-weight adolescents; and 2) to determine the effects of a lifestyle intervention including three months of moderate continuous training (MCT) or high-intensity interval training (HIIT) on health-related parameters and microvascular function in 29 obese adolescents. Body composition, metabolic profile, aerobic fitness and cutaneous blood flow, measured using laser Doppler flowmetry at rest and during post-occlusive reactive hyperemia, were assessed prior to and following lifestyle intervention. Sixteen normal-weight adolescents were included as reference controls for baseline microvascular parameters. At baseline, obese adolescents had higher peak blood flow, peak vascular conductance and area under the curve for post-occlusive reactive hyperemia than normal-weight adolescents. Conversely, peak blood flow, peak vascular conductance and area under the curve data remained unchanged after MCT and HIIT without intergroup differences. However, the peak/basal blood flow ratio decreased in both MCT and HIIT groups without any interaction between groups due to basal CBF increase (tendency p=0.074). Exercise training, whatever the modality, does not improve peak microcirculatory function.

Vitamin D Supplementation on Carotid Remodeling and Stiffness in Obese Adolescents.

Obesity is associated with vitamin D (VD) deficiency and arterial stiffness. This randomized control trial assessed the effects of VD supplementation during a weight-loss program on carotid intima-media thickness (IMT) and carotid compliance in obese adolescents. Participants were randomly assigned to receive either a 12-week lifestyle program with VD supplementation (n = 13), a lifestyle program without VD supplementation (n = 13) or a control group composed of normal-weight adolescents (n = 18). Serum total and free 25-hydroxyvitamin D (25(OH)D), IMT and carotid compliance were measured before and after the trial. Insufficiency in 25(OH)D concentration was found in 73% of obese participants compared to 22% among controls. Obese adolescents had lower free 25(OH)D and displayed higher IMT but lower carotid compliance than controls. Free 25(OH)D and IMT were negatively correlated in adolescents displaying VD insufficiency at baseline. After three months, total and free 25(OH)D increased in both groups. The changes of IMT and carotid compliance were similar between groups. The changes in IMT were correlated with the changes in total 25(OH)D in obese adolescents with VD insufficiency at baseline (r = -0.59, p = 0.03). While the lifestyle program with VD supplementation did not affect carotid compliance, IMT reduction was improved in obese adolescents.

HLA-B7-restricted islet epitopes are differentially recognized in type 1 diabetic children and adults and form weak peptide-HLA complexes.

The cartography of ß-cell epitopes targeted by CD8(+) T cells in type 1 diabetic (T1D) patients remains largely confined to the common HLA-A2 restriction. We aimed to identify ß-cell epitopes restricted by the HLA-B7 (B*07:02) molecule, which is associated with mild T1D protection. Using DNA immunization on HLA-B7-transgenic mice and prediction algorithms, we identified GAD and preproinsulin candidate epitopes. Interferon-γ (IFN-γ) enzyme-linked immunospot assays on peripheral blood mononuclear cells showed that most candidates were recognized by new-onset T1D patients, but not by type 2 diabetic and healthy subjects. Some epitopes were highly immunodominant and specific to either T1D children (GAD(530-538); 44% T cell-positive patients) or adults (GAD(311-320); 38%). All epitopes displayed weak binding affinity and stability for HLA-B7 compared with HLA-A2-restricted ones, a general feature of HLA-B7. Single-cell PCR analysis on ß-cell-specific (HLA-B7 tetramer-positive) T cells revealed uniform IFN-γ and transforming growth factor-ß (TGF-ß) mRNA expression, different from HLA-A2-restricted T cells. We conclude that HLA-B7-restricted islet epitopes display weak HLA-binding profiles, are different in T1D children and adults, and are recognized by IFN-γ(+)TGF-ß(+)CD8(+) T cells. These features may explain the T1D-protective effect of HLA-B7. The novel epitopes identified should find valuable applications for immune staging of HLA-B7(+) individuals.