, Volume 53, Issue 2, pp 530–537 | Cite as

25-Hydroxyvitamin D insufficiency discriminates cardiovascular risk factors accumulation in peri-pubertal boys undergoing overweight screening

  • Andrea Di Nisio
  • Luca De Toni
  • Elvio D’Addato
  • Maria R. Pizzo
  • Pasquale Sabatino
  • Carlo ForestaEmail author
Original Article


The aim of this study was to evaluate the possible association between cardiometabolic risk factors accumulation and vitamin D status in a cohort of Italian normal weight and overweight male children. 108 boys enrolled in an andrological health prevention project underwent physical examination, anthropometric measurements, and fasting blood sampling. Serum blood glucose, HDL-cholesterol, triglycerides, parathyroid hormone, and 25-hydroxyvitamin D (25(OH)D) were measured. Cardiovascular risk factors were defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for age. Lean and overweight subjects differed in terms of waist circumference (P < 0.001), HDL-cholesterol (P = 0.001), triglycerides (P = 0.001), systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.002). Both groups had similar mean 25(OH)D levels (P = 0.160) and were below the sufficiency threshold: indeed only 24 % of normal weight had 25(OH)D ≥30 ng/ml, and even less in the overweight/obese group (8 %, P = 0.03 vs. normal weight). A significant accumulation of risk factors in course of 25(OH)D insufficiency was detected in both the whole cohort and in the normal weight group (P = 0.003 and P = 0.04, respectively) with odd ratios of 1.31 (1.16–1.49 95%CI) and 1.41 (1.18–1.69 95%CI), respectively. In course of vitamin D deficiency, the odd ratios were 2.24 (1.34–3.77 95%CI, P = 0.003) in the whole cohort and 2.40 (1.27–4.82 95%CI, P = 0.03) in lean subjects. We reported a considerable occurrence of cardiovascular risk factors in course of hypovitaminosis D in overweight/obese boys and even in lean subjects, which normally would not have been further evaluated by considering the sole BMI-related parameters. In this regard, 25(OH)D levels appear as a potential discriminating parameter able to identify male children at higher health risk.


Vitamin D Children Obesity Adolescents Cardiovascular risk Metabolic syndrome 


Author Contribution

ADN, LDT, and CF wrote the manuscript, EDA, PS collected the data, MRP performed laboratory assessment, ADN analyzed the data.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest and financial relationships with any organizations that might have an interest in the submitted work. No external funding has been secured for this study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

12020_2015_725_MOESM1_ESM.doc (30 kb)
Supplementary material 1 (DOC 30 kb)
12020_2015_725_MOESM2_ESM.ppt (101 kb)
Supplementary material 2 (PPT 101 kb)


  1. 1.
    G. Jones, S.A. Strugnell, H.F. DeLuca, Current understanding of the molecular actions of vitamin D. Physiol. Rev. 78, 1193–1231 (1998)PubMedGoogle Scholar
  2. 2.
    Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Dietary reference intakes for calcium, magnesium, phosphorus, vitamin D, and fluoride (Food and Nutrition Board, Institute of Medicine National Academy Press, Washington, DC, 1997)Google Scholar
  3. 3.
    P. Pramyothin, M.F. Holick, Vitamin D supplementation: guidelines and evidence for subclinical deficiency. Curr. Opin. Gastroenterol. 28(2), 139–150 (2012). doi: 10.1097/MOG.0b013e32835004dc CrossRefPubMedGoogle Scholar
  4. 4.
    M.F. Holick, N.C. Binkley, H.A. Bischoff-Ferrari, C.M. Gordon, D.A. Hanley, R.P. Heaney, M.H. Murad, C.M. Weaver, Endocrine society: evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 96(7), 1911–1930 (2011). doi: 10.1210/jc.2011-0385 CrossRefPubMedGoogle Scholar
  5. 5.
    M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357, 266–281 (2007). doi: 10.1056/NEJMra070553 CrossRefPubMedGoogle Scholar
  6. 6.
    M.L. Melamed, J. Kumar, Low levels of 25-hydroxyvitamin D in the pediatric populations: prevalence and clinical outcomes. Ped. Health 4(1), 89–97 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Institute of Medicine (US) Standing Committee (IOM), Dietary reference intakes for calcium and vitamin D (National Academies Press, Washington, DC, 2011)Google Scholar
  8. 8.
    J.F. Aloia, The 2011 report on dietary reference intake for vitamin D: where do we go from here? J. Clin. Endocrinol. Metab. 96, 2987–2996 (2011). doi: 10.1210/jc.2011-0090 CrossRefPubMedGoogle Scholar
  9. 9.
    R.P. Heaney, M.F. Holick, Why the IOM recommendations for vitamin D are deficient. J. Bone Miner. Res. 26, 455–457 (2011). doi: 10.1002/jbmr.328 CrossRefPubMedGoogle Scholar
  10. 10.
    M.F. Holick, The D-batable Institute of Medicine report: a D-lightful perspective. Endocr. Pract. 17, 143–149 (2011)CrossRefPubMedGoogle Scholar
  11. 11.
    A.C. Ross, J.E. Manson, S.A. Abrams, J.F. Aloia, P.M. Brannon, S.K. Clinton, R.A. Durazo-Arvizu, J.C. Gallagher, R.L. Gallo, G. Jones, C.S. Kovacs, S.T. Mayne, C.J. Rosen, S.A. Shapses, The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J. Clin. Endocrinol. Metab. 96, 53–58 (2011). doi: 10.1210/jc.2010-2704 CrossRefPubMedGoogle Scholar
  12. 12.
    A. Fraser, D. Williams, D.A. Lawlor, Associations of serum 25-hydroxyvitamin D, parathyroid hormone and calcium with cardiovascular risk factors: analysis of 3 NHANES cycles (2001–2006). PLoS One 5, e13882 (2010). doi: 10.1371/journal.pone.0013882 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    D. Martins, M. Wolf, D. Pan, A. Zadshir, N. Tareen, R. Thadhani, A. Felsenfeld, B. Levine, R. Mehrotra, K. Norris, Prevalence of cardiovascular risk factors and the serum levels of 25- hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch. Intern. Med. 167, 1159–1165 (2007). doi: 10.1001/archinte.167.11.1159 CrossRefPubMedGoogle Scholar
  14. 14.
    R. Scragg, M. Sowers, C. Bell, Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am. J. Hypertens. 20, 713–719 (2007). doi: 10.1016/j.amjhyper.2007.01.017 CrossRefPubMedGoogle Scholar
  15. 15.
    L. Wang, J. Ma, J.E. Manson, J.E. Buring, J.M. Gaziano, H.D. Sesso, A prospective study of plasma vitamin D metabolites, vitamin D receptor gene polymorphisms, and risk of hypertension in men. Eur. J. Nutr. 52(7), 1771–1779 (2013). doi: 10.1007/s00394-012-0480-8 CrossRefPubMedGoogle Scholar
  16. 16.
    A. Zittermann, S. Prokop, The role of vitamin D for cardiovascular disease and overall mortality. Adv. Exp. Med. Biol. 810, 106–119 (2014)PubMedGoogle Scholar
  17. 17.
    K.D. Cashman, A review of vitamin D status and CVD. Proc. Nutr. Soc. 73(1), 65–72 (2014). doi: 10.1017/S0029665113003595 CrossRefPubMedGoogle Scholar
  18. 18.
    L. De Toni, V. De Filippis, S. Tescari, M. Ferigo, A. Ferlin, V. Scattolini, A. Avogaro, R. Vettor, C. Foresta, Uncarboxylated Osteocalcin stimulates 25-hydroxy-vitamin D production in Leydig cell line through a GPRC6A-dependent pathway. Endocrinology 155(11), 4266–4274 (2014). doi: 10.1210/en.2014-1283 CrossRefPubMedGoogle Scholar
  19. 19.
    V. Ganji, X. Zhang, N. Shaikh, V. Tangpricha, Serum 25-hydroxyvitamin D concentrations are associated with prevalence of metabolic syndrome and various cardiometabolic risk factors in US children and adolescents based on assay-adjusted serum 25-hydroxyvitamin D data from NHANES 2001–2006. Am. J. Clin. Nutr. 94, 225–233 (2011). doi: 10.3945/ajcn.111.013516 CrossRefPubMedGoogle Scholar
  20. 20.
    D.S. Freedman, W.H. Dietz, S.R. Srinivasan, G.S. Berenson, The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics 103, 1175–1182 (1999)CrossRefPubMedGoogle Scholar
  21. 21.
    P.G. Kopelman, Obesity as a medical problem. Nature 404(6778), 635–643 (2000)PubMedGoogle Scholar
  22. 22.
    C.L. Ogden, R.J. Kuczmarski, K.M. Flegal, Z. Mei, S. Guo, R. Wei, L.M. Grummer-Strawn, L.R. Curtin, A.F. Roche, C.L. Johnson, Centers for disease control and prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109, 45–60 (2002). doi: 10.1542/peds.109.1.45 CrossRefPubMedGoogle Scholar
  23. 23.
    N.S. The, C. Suchindran, K.E. North, B.M. Popkin, P. Gordon-Larsen, Association of adolescent obesity with risk of severe obesity in adulthood. JAMA 304(18), 2042–2047 (2010). doi: 10.1001/jama.2010.1635 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    P. Björntorp, Obesity. Lancet 350(9075), 423–426 (1997)CrossRefPubMedGoogle Scholar
  25. 25.
    J.M. Tanner, R.H. Whitehouse, Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch. Dis. Child. 51, 170–179 (1976)CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    S. Cook, P. Auinger, C. Li, E.S. Ford, Metabolic syndrome rates in United States adolescents, from the National Health and Nutrition Examination Survey, 1999–2002. J. Pediatr. 152(2), 165–170 (2008). doi: 10.1016/j.jpeds.2007.06.004 CrossRefPubMedGoogle Scholar
  27. 27.
    S. Cook, M. Weitzman, P. Auinger, M. Nguyen, W.H. Dietz, Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Arch. Pediatr. Adolesc. Med. 157(8), 821–827 (2003). doi: 10.1001/archpedi.157.8.821 CrossRefPubMedGoogle Scholar
  28. 28.
    J.R. Fernandez, D.T. Redden, A. Pietrobelli, D.B. Allison, Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J. Pediatr. 145(4), 439–444 (2004)CrossRefPubMedGoogle Scholar
  29. 29.
    M.L. Marcovecchio, F. Chiarelli, Metabolic syndrome in youth: chimera or useful concept? Curr. Diab. Rep. 13(1), 56–62 (2013). doi: 10.1007/s11892-012-0331-2 CrossRefPubMedGoogle Scholar
  30. 30.
    A. Colao, G. Muscogiuri, M. Rubino, L. Vuolo, C. Pivonello, P. Sabatino, M. Pizzo, G. Campanile, R. Fittipaldi, G. Lombardi, C. Di Somma, Hypovitaminosis D in adolescents living in the land of sun is correlated with incorrect life style: a survey study in Campania region. Endocrine 49(2), 521–527 (2015). doi: 10.1007/s12020-014-0483-8 CrossRefPubMedGoogle Scholar
  31. 31.
    B. Franchi, M. Piazza, M. Sandri, L. Tenero, P. Comberiati, A.L. Boner, C. Capristo, 25-hydroxyvitamin D serum level in children of different ethnicity living in Italy. Eur. J. Pediatr. (2014). doi: 10.1007/s00431-014-2451-y Google Scholar
  32. 32.
    J. Valtueña, L. Gracia-Marco, G. Vicente-Rodríguez, M. González-Gross, I. Huybrechts, J.P. Rey-López, T. Mouratidou, I. Sioen, M.I. Mesana, A.E. Martínez, K. Widhalm, L.A. Moreno, HELENA Study Group. Vitamin D status and physical activity interact to improve bone mass in adolescents. The HELENA Study. Osteoporos. Int. 23(8), 2227–2237 (2012)CrossRefPubMedGoogle Scholar
  33. 33.
    F. Vierucci, M. Del Pistoia, M. Fanos, P. Erba, G. Saggese, Prevalence of hypovitaminosis D and predictors of vitamin D status in Italian healthy adolescents. Ital. J. Pediatr. 5, 40–54 (2014). doi: 10.1186/1824-7288-40-54 Google Scholar
  34. 34.
    J.H. Lee, J.H. O’Keefe, D. Bell, D.D. Hensrud, M.F. Holick, Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J. Am. Coll. Cardiol. 52, 1949–1956 (2008). doi: 10.1016/j.jacc.2008.08.050 CrossRefPubMedGoogle Scholar
  35. 35.
    C. Buffington, B. Walker, G.S. Cowan Jr, D. Scruggs, Vitamin D deficiency in the morbidly obese. Obes. Surg. 3, 421–424 (1993)CrossRefPubMedGoogle Scholar
  36. 36.
    J. Wortsman, L.Y. Matsuoka, T.C. Chen, Z. Lu, M.F. Holick, Decreased bioavailability of vitamin D in obesity. Am. J. Clin. Nutr. 72, 690–693 (2000)PubMedGoogle Scholar
  37. 37.
    W.D. Johnson, J.J.M. Kroon, F.L. Greenway, C. Bouchard, D. Ryan, P.T. Katzmarzyk, Prevalence of risk factors for metabolic syndrome in adolescents: national Health and Nutrition Examination Survey (NHANES), 2001–2006. Arch. Pediatr. Adolesc. Med. 163, 371–377 (2009). doi: 10.1001/archpediatrics.2009.3 CrossRefPubMedGoogle Scholar
  38. 38.
    A.R. Folsom, A. Alonso, J.R. Misialek, E.D. Michos, E. Selvin, J.H. Eckfeldt, J. Coresh, J.S. Pankow, P.L. Lutsey, Parathyroid hormone concentration and risk of cardiovascular diseases: the Atherosclerosis Risk in Communities (ARIC) study. Am. Heart J. 168(3), 296–302 (2014). doi: 10.1016/j.ahj.2014.04.017 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    S. Gutiérrez Medina, T. Gavela-Pérez, M.N. Domínguez-Garrido, E. Gutiérrez-Moreno, A. Rovira, C. Garcés, L. Soriano-Guillén, The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance. J. Pediatr. Endocrinol. Metab. 28(1–2), 105–110 (2015). doi: 10.1515/jpem-2014-0033 PubMedGoogle Scholar
  40. 40.
    D.M. Harrington, A.E. Staiano, S.T. Broyles, A.K. Gupta, P.T. Katzmarzyk, BMI percentiles for the identification of abdominal obesity and metabolic risk in children and adolescents: evidence in support of the CDC 95th percentile. Eur. J. Clin. Nutr. 67(2), 218–222 (2013). doi: 10.1038/ejcn.2012.203 CrossRefPubMedGoogle Scholar
  41. 41.
    S.E. Barlow, Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 120, S164–S192 (2007). doi: 10.1542/peds.2007-2329C CrossRefPubMedGoogle Scholar
  42. 42.
    Y. Dong, I.S. Stallmann-Jorgensen, N.K. Pollock, R.A. Harris, D. Keeton, Y. Huang, K. Li, R. Bassali, D.H. Guo, J. Thomas, G.L. Pierce, J. White, M.F. Holick, H. Zhu, A 16-week randomized clinical trial of 2000 international units daily vitamin d-3 supplementation in black youth: 25-hydroxyvitamin d, adiposity, and arterial stiffness. J. Clin. Endocrinol. Metab. 95(10), 4584–4591 (2010). doi: 10.1210/jc.2010-0606 CrossRefPubMedGoogle Scholar
  43. 43.
    E. Klingberg, G. Oleröd, J. Konar, M. Petzold, O. Hammarsten, Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort. Endocrine (2015). doi: 10.1007/s12020-015-0548-3 PubMedPubMedCentralGoogle Scholar
  44. 44.
    D.P. Choi, S.M. Oh, J.M. Lee, H.M. Cho, W.J. Lee, B.M. Song, Y. Rhee, H.C. Kim, Serum 25-hydroxyvitamin D and insulin resistance in apparently healthy adolescents. PLoS One 9(7), e103108 (2014). doi: 10.1371/journal.pone.0103108 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    E. Giovannucci, Y. Liu, B.W. Hollis, E.B. Rimm, 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch. Intern. Med. 168, 1174–1180 (2008). doi: 10.1001/archinte.168.11.1174 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Andrea Di Nisio
    • 1
  • Luca De Toni
    • 1
  • Elvio D’Addato
    • 2
  • Maria R. Pizzo
    • 2
  • Pasquale Sabatino
    • 3
  • Carlo Foresta
    • 1
    Email author
  1. 1.Department of Medicine, Unit of Andrology and Human Reproductive MedicineUniversity of PadovaPaduaItaly
  2. 2.U.O. Medicina P.O.Sapri (Salerno)Italy
  3. 3.Asl Salerno and Asl Napoli 3/sudSalernoItaly

Personalised recommendations