About this Journal Submit a Manuscript Table of Contents
International Journal of Endocrinology
Volume 2013 (2013), Article ID 148673, 10 pages
http://dx.doi.org/10.1155/2013/148673
Review Article

The Role of Vitamin D Deficiency in the Incidence, Progression, and Complications of Type 1 Diabetes Mellitus

Department of Internal Medicine, Division of Endocrinology and Metabolism, American University of Beirut-Medical Center, 3 Dag Hammarskjold Plaza, 8th floor, New York, NY 10017, USA

Received 19 November 2012; Revised 23 January 2013; Accepted 29 January 2013

Academic Editor: Guang-Da Xiang

Copyright © 2013 Marlene Chakhtoura and Sami T. Azar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. C. Harrison, M. C. Honeyman, G. Morahan et al., “Type 1 diabetes: lessons for other autoimmune diseases?” Journal of Autoimmunity, vol. 31, no. 3, pp. 306–310, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. M. E. Craig, A. Hattersley, and K. Donaghue, “Definition, epidemiology and classification of diabetes in children and adolescents,” Pediatric Diabetes, vol. 7, no. 10, supplement 12, pp. 3–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. N. Lammi, O. Taskinen, E. Moltchanova et al., “A high incidence of type 1 diabetes and an alarming increase in the incidence of type 2 diabetes among young adults in Finland between 1992 and 1996,” Diabetologia, vol. 50, no. 7, pp. 1393–1400, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. G. P. Forlenza and M. Rewers, “The epidemic of type 1 diabetes: what is it telling us?” Current Opinion in Endocrinology, Diabetes and Obesity, vol. 18, no. 4, pp. 248–251, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. L. Moroni, I. Bianchi, and A. Lleo, “Geoepidemiology, gender and autoimmune disease,” Autoimmunity Reviews, vol. 11, pp. A386–A392, 2012.
  6. M. A. Kriegel, J. E. Manson, and K. H. Costenbader, “Does vitamin D affect risk of developing autoimmune disease?: a systematic review,” Seminars in Arthritis and Rheumatism, vol. 40, no. 6, pp. 512–531, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Cutolo, C. Pizzorni, and A. Sulli, “Vitamin D endocrine system involvement in autoimmune rheumatic diseases,” Autoimmunity Reviews, vol. 11, pp. 84–87, 2011.
  8. S. Nagpal, S. Na, and R. Rathnachalam, “Noncalcemic actions of vitamin D receptor ligands,” Endocrine Reviews, vol. 26, no. 5, pp. 662–687, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. E. van Etten and C. Mathieu, “Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts,” Journal of Steroid Biochemistry and Molecular Biology, vol. 97, no. 1-2, pp. 93–101, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Lee, S. A. Clark, R. K. Gill, and S. Christakos, “1,25-Dihydroxyvitamin D3 and pancreatic β-cell function: vitamin D receptors, gene expression, and insulin secretion,” Endocrinology, vol. 134, no. 4, pp. 1602–1610, 1994. View at Publisher · View at Google Scholar · View at Scopus
  11. J. B. Zella, L. C. McCary, and H. F. DeLuca, “Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus,” Archives of Biochemistry and Biophysics, vol. 417, no. 1, pp. 77–80, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. A. Giulietti, C. Gysemans, K. Stoffels et al., “Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice,” Diabetologia, vol. 47, no. 3, pp. 451–462, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Mathieu, J. Laureys, H. Sobis, M. Vandeputte, M. Waer, and R. Bouillon, “1,25-Dihydroxyvitamin D3 prevents insulitis in NOD mice,” Diabetes, vol. 41, no. 11, pp. 1491–1495, 1992. View at Scopus
  14. K. M. Casteels, C. Mathieu, M. Waer, et al., “Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-dihydroxyvitamin D3, KH1060,” Endocrinology, vol. 136, no. 3, pp. 866–872, 1995. View at Scopus
  15. C. A. Gysemans, A. K. Cardozo, H. Callewaert et al., “1,25-Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in nonobese diabetic mice,” Endocrinology, vol. 146, no. 4, pp. 1956–1964, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. N. Giarratana, G. Penna, S. Amuchastegui, R. Mariani, K. C. Daniel, and L. Adorini, “A vitamin D analog down-regulates proinflammatory chemokine production by pancreatic islets inhibiting T cell recruitment and type 1 diabetes development,” Journal of Immunology, vol. 173, no. 4, pp. 2280–2287, 2004. View at Scopus
  17. S. Gregori, N. Giarratana, S. Smiroldo, M. Uskokovic, and L. Adorini, “A 1α,25-dihydroxyvitamin D3 analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice,” Diabetes, vol. 51, no. 5, pp. 1367–1374, 2002. View at Scopus
  18. R. Riachy, B. Vandewalle, S. Belaich et al., “Beneficial effect of 1,25 dihydroxyvitamin D3 on cytokine-treated human pancreatic islets,” Journal of Endocrinology, vol. 169, no. 1, pp. 161–168, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. J. A. Emamaullee, J. Davis, S. Merani et al., “Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice,” Diabetes, vol. 58, no. 6, pp. 1302–1311, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Arnson, H. Amital, and Y. Shoenfeld, “Vitamin D and autoimmunity: new aetiological and therapeutic considerations,” Annals of the Rheumatic Diseases, vol. 66, no. 9, pp. 1137–1142, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. C. Mathieu, M. Waer, J. Laureys, O. Rutgeerts, and R. Bouillon, “Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3,” Diabetologia, vol. 37, no. 6, pp. 552–558, 1994. View at Scopus
  22. C. Mathieu, M. Waer, K. Casteels, J. Laureys, and R. Bouillon, “Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-dihydroxyvitamin D3, KH1060,” Endocrinology, vol. 136, no. 3, pp. 866–872, 1995. View at Scopus
  23. L. Overbergh, B. Decallonne, M. Waer et al., “1α,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524–543),” Diabetes, vol. 49, no. 8, pp. 1301–1307, 2000. View at Scopus
  24. A. L. Khoo, I. Joosten, and M. Michels, “1, 25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells,” Immunology, vol. 134, no. 4, pp. 459–468, 2011.
  25. R. Riachy, B. Vandewalle, J. K. Conte et al., “1,25-dihydroxyvitamin D3 protects RINm5F and human islet cells against cytokine-induced apoptosis: implication of the antiapoptotic protein A20,” Endocrinology, vol. 143, no. 12, pp. 4809–4819, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Y. Savinov, A. Tcherepanov, and E. A. Green, “Contribution of Fas to diabetes development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, pp. 628–632, 2003.
  27. R. Riachy, B. Vandewalle, E. Moerman et al., “1,25-dihydroxyvitamin D3 protects human pancreatic islets against cytokine-induced apoptosis via down-regulation of the Fas receptor,” Apoptosis, vol. 11, no. 2, pp. 151–159, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Nagpal, S. Na, and R. Rathnachalam, “Noncalcemic actions of vitamin D receptor ligands,” Endocrine Reviews, vol. 26, no. 5, pp. 662–687, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. A. G. Uitterlinden, Y. Fang, J. B. J. Van Meurs, H. A. P. Pols, and J. P. T. M. Van Leeuwen, “Genetics and biology of vitamin D receptor polymorphisms,” Gene, vol. 338, no. 2, pp. 143–156, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. A. F. Reis, O. M. Hauache, and G. Velho, “Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity and vascular disease. A review of evidence,” Diabetes and Metabolism, vol. 31, no. 4, part 1, pp. 318–325, 2005. View at Scopus
  31. E. Ramos-Lopez, T. Jansen, V. Ivaskevicius et al., “Protection from type 1 diabetes by vitamin D receptor haplotypes,” Annals of the New York Academy of Sciences, vol. 1079, pp. 327–334, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. M. F. McDermott, A. Ramachandran, B. W. Ogunkolade et al., “Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians,” Diabetologia, vol. 40, no. 8, pp. 971–975, 1997. View at Publisher · View at Google Scholar · View at Scopus
  33. N. Israni, R. Goswami, A. Kumar, and R. Rani, “Interaction of Vitamin D receptor with HLA DRB1*0301 in Type 1 diabetes patients from North India,” PLoS ONE, vol. 4, no. 12, Article ID e8023, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. Z. Mohammadnejad, M. Ghanbari, R. Ganjali et al., “Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population,” Molecular Biology Reports, vol. 39, no. 2, pp. 831–837, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. G. Martí, L. Audí, C. Esteban et al., “Association of vitamin D receptor gene polymorphism with type 1 diabetes mellitus in two Spanish populations,” Medicina Clinica, vol. 123, no. 8, pp. 286–290, 2004. View at Scopus
  36. S. Nejentsev, J. D. Cooper, L. Godfrey et al., “Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes,” Diabetes, vol. 53, no. 10, pp. 2709–2712, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. C. Guja, S. Marshall, K. Welsh et al., “The study of CTLA-4 and vitamin D receptor polymorphisms in the Romanian type 1 diabetes population,” Journal of Cellular and Molecular Medicine, vol. 6, no. 1, pp. 75–81, 2002. View at Scopus
  38. S. B. Sahin, S. Cetinkalp, and M. Erdogan, “Fas, Fas ligand, and vitamin D receptor fokI gene polymorphisms in patients with Type 1 diabetes mellitus in the aegean region of Turkey,” Genet Test Mol Biomarkers, vol. 16, no. 10, pp. 1179–1183, 2012.
  39. D. Gogas Yavuz, L. Keskin, S. Kıyıcı, et al., “Vitamin D receptor gene BsmI, FokI, ApaI, TaqI polymorphisms and bone mineral density in a group of Turkish type 1 diabetic patients,” Acta Diabetologica, vol. 48, no. 4, pp. 329–336, 2011.
  40. B. Györffy, B. Vásárhelyi, D. Krikovszky et al., “Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus,” European Journal of Endocrinology, vol. 147, no. 6, pp. 803–808, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Lemosa, A. Fagulhab, and E. Coutinhoc, “Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population,” Human Immunology, vol. 69, pp. 134–138, 2008.
  42. A. Shimada, Y. Kanazawa, Y. Motohashi et al., “Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese,” Journal of Autoimmunity, vol. 30, no. 4, pp. 207–211, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. Y. Ban, M. Taniyama, T. Yanagawa et al., “Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population,” BMC Medical Genetics, vol. 2, article 7, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Turpeinen, R. Hermann, S. Vaara et al., “Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population,” European Journal of Endocrinology, vol. 149, no. 6, pp. 591–596, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Fichna, M. Zurawek, D. Januszkiewicz-Lewandowska, P. Fichna, and J. Nowak, “PTPN22, PDCD1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Polish patients,” International Journal of Immunogenetics, vol. 37, no. 5, pp. 367–372, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. V. Boraska, V. Škrabić, E. Zeggini et al., “Family-based analysis of vitamin D receptor gene polymorphisms and type 1 diabetes in the population of South Croatia,” Journal of Human Genetics, vol. 53, no. 3, pp. 210–214, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Zemunik, V. Škrabić, V. Boraska et al., “Fokl polymorphism, vitamin D receptor, and interleukin-1 receptor haplotypes are associated with type 1 diabetes in the Dalmatian population,” Journal of Molecular Diagnostics, vol. 7, no. 5, pp. 600–604, 2005. View at Scopus
  48. D. B. Mory, E. R. Rocco, W. L. Miranda, T. Kasamatsu, F. Crispim, and S. A. Dib, “Prevalence of vitamin D receptor gene polymorphisms FokI and BsmI in Brazilian individuals with type 1 diabetes and their relation to β-cell autoimmunity and to remaining β-cell function,” Human Immunology, vol. 70, no. 6, pp. 447–451, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Mimbacas, J. Trujillo, C. Gascue, G. Javiel, and H. Cardoso, “Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus,” Genetics and Molecular Research, vol. 6, no. 3, pp. 534–542, 2007. View at Scopus
  50. W. J. Fassbender, B. Goertz, K. Weismüller et al., “VDR gene polymorphisms are overrepresented in German patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism,” Hormone and Metabolic Research, vol. 34, no. 6, pp. 330–337, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. M. A. Pani, M. Knapp, H. Donner et al., “Vitamin D receptor allele combinations influence genetic susceptibility to 1 diabetes in Germans,” Diabetes, vol. 49, no. 3, pp. 504–507, 2000. View at Scopus
  52. E. Ramos-Lopez, T. Jansen, V. Ivaskevicius et al., “Protection from type 1 diabetes by vitamin D receptor haplotypes,” Annals of the New York Academy of Sciences, vol. 1079, pp. 327–334, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Panierakis, G. Goulielmos, D. Mamoulakis, E. Petraki, E. Papavasiliou, and E. Galanakis, “Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece,” Clinical Immunology, vol. 133, no. 2, pp. 276–281, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. B. W. Ogunkolade, B. J. Boucher, J. M. Prahl et al., “Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians,” Diabetes, vol. 51, no. 7, pp. 2294–2300, 2002. View at Scopus
  55. T. J. Chang, H. H. Lei, J. I. Yeh et al., “Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population,” Clinical Endocrinology, vol. 52, no. 5, pp. 575–580, 2000. View at Publisher · View at Google Scholar · View at Scopus
  56. D. García, B. Angel, E. Carrasco, C. Albala, J. L. Santos, and F. Pérez-Bravo, “VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago, Chile,” Diabetes Research and Clinical Practice, vol. 77, no. 1, pp. 134–140, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. M. G. Bianco, L. Minicucci, M. G. Calevo, and R. Lorini, “Vitamin D receptor polymorphisms: are they really associated with type 1 diabetes?” European Journal of Endocrinology, vol. 151, no. 5, pp. 641–642, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. A. L. Ponsonby, A. Pezic, J. Ellis et al., “Variation in associations between allelic variants of the vitamin D receptor gene and onset of type 1 diabetes mellitus by ambient winter ultraviolet radiation levels: a meta-regression analysis,” American Journal of Epidemiology, vol. 168, no. 4, pp. 358–365, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. E. Van Etten, L. Verlinden, A. Giulietti et al., “The vitamin D receptor gene FokI polymorphism: functional impact on the immune system,” European Journal of Immunology, vol. 37, no. 2, pp. 395–405, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Zhang, W. Li, and J. Liu, “Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: an update by meta-analysis,” Molecular and Cellular Endocrinology, vol. 355, pp. 135–142, 2012.
  61. M. Janner, P. Ballinari, P. E. Mullis, and C. E. Flück, “High prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes,” Swiss Medical Weekly, vol. 140, p. w13091, 2010. View at Scopus
  62. A. Bener, A. Alsaied, M. Al-Ali et al., “High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children,” Acta Diabetologica, vol. 46, no. 3, pp. 183–189, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. V. V. Borkar, V. S. Devidayal, and A. K. Bhalla, “Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes,” Pediatric Diabetes, vol. 11, no. 5, pp. 345–350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. B. M. Svoren, L. K. Volkening, J. R. Wood, and L. M. B. Laffel, “Significant vitamin D deficiency in youth with type 1 diabetes mellitus,” Journal of Pediatrics, vol. 154, no. 1, pp. 132–134, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. P. Pozzilli, S. Manfrini, A. Crinò, et al., “Low levels of 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes,” Hormone and Metabolic Research, vol. 37, no. 11, pp. 680–683, 2005.
  66. R. M. Greer, S. L. Portelli, and B. S. Hung, “Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes,” Pediatric Diabetes, vol. 14, no. 1, pp. 31–41, 2012. View at Publisher · View at Google Scholar
  67. E. A. Hamed, N. H. Faddan, and H. A. Elhafeez, “Parathormone—25(OH)-vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus,” Pediatr Diabete, vol. 12, no. 6, pp. 536–546, 2011.
  68. O. Rodland, T. Markestad, L. Aksnes, and D. Aarskog, “Plasma concentration of vitamin D metabolites during puberty of diabetic children,” Diabetologia, vol. 28, no. 9, pp. 663–666, 1985. View at Scopus
  69. B. Littorin, P. Blom, A. Schölin et al., “Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS),” Diabetologia, vol. 49, no. 12, pp. 2847–2852, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Bierschenk, J. Alexander, C. Wasserfall, M. Haller, D. Schatz, and M. Atkinson, “Vitamin D levels in subjects with and without type 1 diabetes residing in a solar rich environment,” Diabetes Care, vol. 32, no. 11, pp. 1977–1979, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. D. J. Di Cesar, R. Ploutz-Snyder, R. S. Weinstock, and A. M. Moses, “Vitamin D deficiency is more common in type 2 than in type 1 diabetes [6],” Diabetes Care, vol. 29, no. 1, p. 174, 2006. View at Scopus
  72. H. F. DeLuca, “Overview of general physiologic features and functions of vitamin D,” The American Journal of Clinical Nutrition, vol. 80, no. 6, supplement, pp. 1689S–1696S, 2004.
  73. J. A. Staples, A. L. Ponsonby, L. L. Y. Lim, and A. J. McMichael, “Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: iatitude, regional ultraviolet radiation, and disease prevalence,” Environmental Health Perspectives, vol. 111, no. 4, pp. 518–523, 2003. View at Scopus
  74. L. Nystrom, G. Dahlquist, J. Ostman et al., “Risk of developing insulin-dependent diabetes mellitus (IDDM) before 35 years of age: indications of climatological determinants for age at onset,” International Journal of Epidemiology, vol. 21, no. 2, pp. 352–358, 1992. View at Scopus
  75. Z. Yang, K. Wang, L. I. Tianlin et al., “Childhood diabetes in China: enormous variation by place and ethnic group,” Diabetes Care, vol. 21, no. 4, pp. 525–529, 1998. View at Publisher · View at Google Scholar · View at Scopus
  76. G. Joner, L. C. Stene, and O. Søvik, “Nationwide, prospective registration of type 1 diabetes in children aged <15 years in Norway 1989–1998: no increase but significant regional variation in incidence,” Diabetes Care, vol. 27, no. 7, pp. 1618–1622, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. “Variation and trends in incidence of childhood diabetes in Europe,” The Lancet, vol. 355, no. 9207, pp. 873–876, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Casu, C. Pascutto, L. Bernardinelli, and M. Songini, “Bayesian approach to study the temporal trend and the geographical variation in the risk of type 1 diabetes: the Sardinian Conscript type 1 diabetes registry,” Pediatric Diabetes, vol. 5, no. 1, pp. 32–38, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. S. B. Mohr, C. F. Garland, E. D. Gorham, and F. C. Garland, “The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide,” Diabetologia, vol. 51, no. 8, pp. 1391–1398, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. T. R. Merriman, “Type 1 diabetes, the A1 milk hypothesis and vitamin D deficiency,” Diabetes Research and Clinical Practice, vol. 83, no. 2, pp. 149–156, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. A. M. Vaiserman, B. Carstensen, V. P. Voitenko et al., “Seasonality of birth in children and young adults (0-29 years) with type 1 diabetes in Ukraine,” Diabetologia, vol. 50, no. 1, pp. 32–35, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. U. Samuelsson, C. Johansson, and J. Ludvigsson, “Month of birth and risk of developing insulin dependent diabetes in south east Sweden,” Archives of Disease in Childhood, vol. 81, no. 2, pp. 143–146, 1999. View at Scopus
  83. M. I. Kalliora, A. Vazeou, D. Delis, E. Bozas, I. Thymelli, and C. S. Bartsocas, “Seasonal variation of type 1 diabetes mellitus diagnosis in Greek children,” Hormones, vol. 10, no. 1, pp. 67–71, 2011. View at Scopus
  84. E. F. Roche, H. Lewy, H. M. C. V. Hoey, and Z. Laron, “Differences between males and females in the seasonality of birth and month of clinical onset of disease in chilren with type 1 diabetes mellitus in Ireland,” Journal of Pediatric Endocrinology and Metabolism, vol. 16, no. 5, pp. 779–782, 2003. View at Scopus
  85. N. Ursic-Bratina, T. Battelino, C. Kržišnik, T. Laron-Kenet, I. Ashkenazi, and Z. Laron, “Seasonality of birth in children (0–14 years) with type 1 diabetes mellitus in Slovenia,” Journal of Pediatric Endocrinology and Metabolism, vol. 14, no. 1, pp. 47–52, 2001. View at Scopus
  86. O. Kordonouri, N. Shuga, H. Lewy, I. Ashkenazi, and Z. Laron, “Seasonality of month of birth of children and adolescents with type 1 diabetes mellitus in Berlin differs from the general population,” European Journal of Pediatrics, vol. 161, no. 5, pp. 291–292, 2002. View at Publisher · View at Google Scholar · View at Scopus
  87. P. H. Jongbloet, H. M. Groenewoud, R. A. Hirasing, and S. Van Buuren, “Seasonality of birth in patients with childhood diabetes in The Netherlands,” Diabetes Care, vol. 21, no. 1, pp. 190–191, 1998. View at Scopus
  88. P. M. Rothwell, A. Staines, P. Smail, E. Wadsworth, and P. McKinney, “Seasonality of birth of patients with childhood diabetes in Britain,” British Medical Journal, vol. 312, no. 7044, pp. 1456–1457, 1996. View at Scopus
  89. J. A. Willis, R. S. Scott, B. A. Darlow, H. Lewy, I. Ashkenazi, and Z. Laron, “Seasonality of birth and onset of clinical disease in children and adolescents (0–19 years) with type 1 diabetes mellitus in Canterbury, New Zealand,” Journal of Pediatric Endocrinology and Metabolism, vol. 15, no. 5, pp. 645–647, 2002. View at Scopus
  90. M. Songini, A. Casu, I. Ashkenazi, and Z. Laron, “Seasonality of birth in children (0–14 years) and young adults (0–29 years) with type 1 diabetes mellitus in Sardinia differs from that in the general population,” Journal of Pediatric Endocrinology and Metabolism, vol. 14, no. 6, pp. 781–783, 2001. View at Scopus
  91. P. M. Rothwell, S. A. Gutnikov, P. A. McKinney, E. Schober, C. Ionescu-Tirgoviste, and A. Neu, “Seasonality of birth in children with diabetes in Europe: multicentre cohort study,” British Medical Journal, vol. 319, no. 7214, pp. 887–888, 1999. View at Scopus
  92. T. Bock, C. R. Pedersen, A. Volund, C. S. Pallesen, and K. Buschard, “Perinatal determinants among children who later develop IDDM,” Diabetes Care, vol. 17, no. 10, pp. 1154–1157, 1994. View at Scopus
  93. K. El Baba, M. S. Zantout, A. Arabi, and S. T. Azar, “Seasonal variations of glucose control in Lebanese patients with type 1 diabetes,” Biological Rhythm Research, vol. 41, no. 2, pp. 91–97, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. K. El Baba, M. Zantout, R. Akel, and S. Azar, “Seasonal variation in vitamin D and HbA(1c) levels in patients with type 1 diabetes mellitus in the Middle East,” International Journal of General Medicine, vol. 4, pp. 635–638, 2011.
  95. Z. Laron, H. Lewy, I. Wilderman et al., “Seasonality of month of birth of children and adolescents with type 1 diabetes mellitus in homogenous and heterogeneous populations,” Israel Medical Association Journal, vol. 7, no. 6, pp. 381–384, 2005. View at Scopus
  96. “Vitamin D supplement in early childhood and risk for Type I (insulin- dependent) diabetes mellitus,” Diabetologia, vol. 42, no. 1, pp. 51–54, 1999. View at Publisher · View at Google Scholar · View at Scopus
  97. E. Hyppönen, E. Läärä, A. Reunanen, M. R. Järvelin, and S. M. Virtanen, “Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study,” The Lancet, vol. 358, no. 9292, pp. 1500–1503, 2001.
  98. L. C. Stene, J. Ulriksen, P. Magnus, and G. Joner, “Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring,” Diabetologia, vol. 43, no. 9, pp. 1093–1098, 2000. View at Publisher · View at Google Scholar · View at Scopus
  99. L. C. Stene and G. Joner, “Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study,” American Journal of Clinical Nutrition, vol. 78, no. 6, pp. 1128–1134, 2003. View at Scopus
  100. C. M. Fronczak, A. E. Barón, H. P. Chase et al., “In utero dietary exposures and risk of islet autoimmunity in children,” Diabetes Care, vol. 26, no. 12, pp. 3237–3242, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. M. T. Tenconi, G. Devoti, M. Comelli et al., “Major childhood infectious diseases and other determinants associated with type 1 diabetes: a case-control study,” Acta Diabetologica, vol. 44, no. 1, pp. 14–19, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. H. K. Brekke and J. Ludvigsson, “Vitamin D supplementation and diabetes-related autoimmunity in the ABIS study,” Pediatric Diabetes, vol. 8, no. 1, pp. 11–14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. L. Marjamäki, S. Niinistö, M. G. Kenward, et al., “Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring,” Diabetologia, vol. 53, no. 8, pp. 1599–1607, 2010.
  104. C. S. Zipitis and A. K. Akobeng, “Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis,” Archives of Disease in Childhood, vol. 93, no. 6, pp. 512–517, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. A. Antico, M. Tampoia, R. Tozzoli, and N. Bizzaro, “Can supplementation with Vitamin D reduce the risk or modify the course of autoimmune diseases? A systamatic review of the literature,” Autoimmunity Reviews, vol. 12, pp. 127–136, 2012.
  106. B. L. Nyomba, J. Verhaeghe, M. Thomasset, W. Lissens, and R. Bouillon, “Bone mineral homeostasis in spontaneously diabetic BB rats. I. Abnormal vitamin D metabolism and impaired active intestinal calcium absorption,” Endocrinology, vol. 124, no. 2, pp. 565–572, 1989. View at Scopus
  107. K. M. Thrailkill, C. H. Jo, and G. E. Cockrell, “Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency?” The Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 1, pp. 142–149, 2011.
  108. T. Huynh, R. M. Greer, O. Nyunt et al., “The association between ketoacidosis and 25(OH)-vitamin D3 levels at presentation in children with type 1 diabetes mellitus,” Pediatric Diabetes, vol. 10, no. 1, pp. 38–43, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Devaraj, J. M. Yun, C. R. Duncan-Staley, and I. Jialal, “Low vitamin d levels correlate with the proinflammatory state in type 1 diabetic subjects with and without microvascular complications,” American Journal of Clinical Pathology, vol. 135, no. 3, pp. 429–433, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Verrotti, F. Basciani, F. Carle, G. Morgese, and F. Chiarelli, “Calcium metabolism in adolescents and young adults with type 1 diabetes mellitus without and with persistent microalbuminuria,” Journal of Endocrinological Investigation, vol. 22, no. 3, pp. 198–202, 1999. View at Scopus
  111. S. Judd, V. Tangpricha, and D. Vitamin, “Deficiency and risk for cardiovascular disease,” Circulation, vol. 117, no. 4, pp. 503–511, 2008.
  112. D. Pitocco, A. Crinò, E. Di Stasio et al., “The effects of calcitriol and nicotinamide on residual pancreatic β-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI),” Diabetic Medicine, vol. 23, no. 8, pp. 920–923, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Bizzarri, D. Pitocco, N. Napoli et al., “No protective effect of calcitriol on β-cell function in recent-onset type 1 diabetes: the IMDIAB XIII trial,” Diabetes Care, vol. 33, no. 9, pp. 1962–1963, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. X. Li, L. Liao, X. Yan et al., “Protective effects of 1-α-hydroxyvitamin D3 on residual β-cell function in patients with adult-onset latent autoimmune diabetes (LADA),” Diabetes/Metabolism Research and Reviews, vol. 25, no. 5, pp. 411–416, 2009. View at Publisher · View at Google Scholar · View at Scopus
  115. K. S. Aljabri, S. A. Bokhari, and M. J. Khan, “Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency,” Annals of Saudi Medicine, vol. 30, no. 6, pp. 454–508, 2010. View at Publisher · View at Google Scholar · View at Scopus
  116. C. L. Wagner and F. R. Greer, “Prevention of rickets and vitamin D deficiency in infants, children, and adolescents,” Pediatrics, vol. 122, no. 5, pp. 1142–1152, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. A. C. Ross, J. E. Manson, S. A. Abrams et al., “The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know,” Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 1, pp. 53–58, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. S. Harris, “Can vitamin D supplementation in infancy prevent type 1 diabetes?” Nutrition Reviews, vol. 60, no. 4, pp. 118–121, 2002. View at Publisher · View at Google Scholar · View at Scopus
  119. M. Holick, N. Binkley, H. Bischoff-Ferrari, et al., “Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline,” The Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 7, pp. 1911–1930, 2011.
  120. G. Penna and L. Adorini, “1α,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation,” Journal of Immunology, vol. 164, no. 5, pp. 2405–2411, 2000. View at Scopus
  121. L. Piemonti, P. Monti, M. Sironi et al., “Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells,” Journal of Immunology, vol. 164, no. 9, pp. 4443–4451, 2000. View at Scopus