title: Vitamin D deficiency in childhood obesity is associated with high levels of circulating inflammatory mediators, and low insulin sensitivity.
abstract: OBJECTIVE
  Childhood obesity is accompanied by low-grade systemic inflammation, which contributes to the development of insulin resistance and cardiovascular complications later in life. As vitamin D exhibits profound immunomodulatory functions and vitamin D deficiency is highly prevalent in childhood obesity, we hypothesized that vitamin D deficiency in childhood obesity coincides with enhanced systemic inflammation and reduced insulin sensitivity.
  
  
  METHODS
  In a cross-sectional study of 64 obese and 32 healthy children aged 6-16 years, comprehensive profiling of 32 circulating inflammatory mediators was performed, together with assessment of 25-hydroxyvitamin D (25(OH)D) levels and measures for insulin sensitivity.
  
  
  RESULTS
  Severe vitamin D insufficiency, which is further referred to as vitamin D deficiency, was defined as a 25(OH)D level ≤37.5 nmol l(-1), and was highly prevalent in obese (56%) versus healthy control children (16%). Throughout the study, 25(OH)D-deficient children were compared with the other children, including 25(OH)D insufficient (37.5-50 nmol l(-1)) and 25(OH)D sufficient children (≥50 nmol l(-1)). First, 25(OH)D-deficient obese children showed a lower insulin sensitivity than other obese children, as measured by a lower quantitative insulin sensitivity check index. Second, the association between 25(OH)D deficiency and insulin resistance in childhood obesity was confirmed with multiple regression analysis. Third, 25(OH)D-deficient obese children showed higher levels of the inflammatory mediators cathepsin S, chemerin and soluble vascular adhesion molecule (sVCAM), compared with the other obese children. Finally, hierarchical cluster analysis revealed an over-representation of 25(OH)D deficiency in obese children expressing inflammatory mediator clusters with high levels of cathepsin S, sVCAM and chemerin.
  
  
  CONCLUSIONS
  25(OH)D deficiency in childhood obesity was associated with enhanced systemic inflammation and reduced insulin sensitivity. The high cathepsin S and sVCAM levels may reflect activation of a pro-inflammatory, pro-diabetic and atherogenic pathway, which could be inhibited by vitamin D supplementation.
authors.affiliation: Department of Pediatric Immunology and Center for Molecular and Cellular Intervention, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Reyman
authors.affiliation: 1] Department of Pediatric Immunology and Center for Molecular and Cellular Intervention, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands [2] Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: Verrijn Stuart
authors.affiliation: Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Summeren
authors.affiliation: Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Rakhshandehroo
authors.affiliation: Department of Pediatrics, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Nuboer
authors.affiliation: Department of Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
authors.forename: F K
authors.initials: FK
authors.lastname: de Boer
authors.affiliation: Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: van den Ham
authors.affiliation: Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Kalkhoven
authors.affiliation: Department of Pediatric Immunology and Center for Molecular and Cellular Intervention, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Prakken
authors.affiliation: 1] Department of Pediatric Immunology and Center for Molecular and Cellular Intervention, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands [2] Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H S
authors.initials: HS
authors.lastname: Schipper
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D018925:Chemokines / Q000097:blood; D002648:Child; D016000:Cluster Analysis; D003324:Coronary Artery Disease / Q000517:prevention & control*; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance / Q000276:immunology; D008297:Male; D063766:Pediatric Obesity / Q000097:blood / Q000150:complications* / Q000276:immunology; D015995:Prevalence; D014807:Vitamin D / Q000031:analogs & derivatives / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications* / Q000276:immunology; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D018925:Chemokines; D018836:Inflammation Mediators; D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D