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The Role of Vitamin D in the Metabolic Homeostasis of Diabetic Bone

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Abstract

Most studies across a variety of geographic locations suggest that vitamin D insufficiency is more common in individuals with type 1 diabetes (T1D) compared to the general population. In type 2 diabetes (T2D), while obesity is commonplace and lower vitamin D levels are present in obese adolescents and adults, the association between vitamin D insufficiency and T2D is less clear. Studies suggest that the relationship between T2D and vitamin D may be concurrently influenced by ethnicity, geography, BMI and age. Nonetheless, diabetic osteopathy is a significant comorbidity of both forms of diabetes and is characterized by micro-architectural changes that decrease bone quality leading to an increased risk for bone fracture in both disorders. The question remains, however, to what degree vitamin D homeostasis contributes to or exacerbates skeletal pathology in diabetes. Proposed mechanisms for vitamin D deficiency in diabetes include (1) genetic predisposition (T1D); (2) increased BMI (T2D); (3) concurrent albuminuria (T1D or T2D); or (4) exaggerated renal excretion of vitamin D metabolites or vitamin D-binding protein (T1D, T2D, animal models). The specific effects of vitamin D treatment on diabetic osteoporosis have been examined in rodents and demonstrate skeletal improvements even in the face of untreated diabetes. However, human clinical trial data examining whether vitamin D status can be directly related to or it is predictive of bone quality and fracture risk in those with diabetes are still needed. Herein, we provide a review of the literature linking vitamin D, diabetes and skeletal health.

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References

  1. Nyman JS, Even JL, Jo CH, et al. Increasing duration of type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone. Bone. 2011;48:733–40.

    Article  PubMed  Google Scholar 

  2. Thrailkill KM, Lumpkin CK Jr, Bunn RC, Kemp SF, Fowlkes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab. 2005;289:E735–45.

    Article  CAS  PubMed  Google Scholar 

  3. Pasoto SG, Yoshihara LA, Maeda LC, et al. Osteoporotic hip fractures in non-elderly patients: relevance of associated co-morbidities. Rheumatol Int. 2011 [Epub ahead of print]. doi:10.1007/s00296-011-2154-x

  4. Holmberg AH, Johnell O, Nilsson PM, Nilsson JA, Berglund G, Akesson K. Risk factors for hip fractures in a middle-aged population: a study of 33,000 men and women. Osteoporos Int. 2005;16:2185–94.

    Article  PubMed  Google Scholar 

  5. Svoren BM, Volkening LK, Wood JR, Laffel LM. Significant vitamin D deficiency in youth with type 1 diabetes mellitus. J Pediatr. 2009;154:132–4.

    Article  PubMed  Google Scholar 

  6. Frazer TE, White NH, Hough S, et al. Alterations in circulating vitamin D metabolites in the young insulin-dependent diabetic. J Clin Endocrinol Metab. 1981;53:1154–9.

    Article  CAS  PubMed  Google Scholar 

  7. Bener A, Alsaied A, Al-Ali M, et al. Impact of lifestyle and dietary habits on hypovitaminosis D in type 1 diabetes mellitus and healthy children from Qatar, a sun-rich country. Ann Nutr Metab. 2008;53:215–22.

    Article  CAS  PubMed  Google Scholar 

  8. Tahrani AA, Ball A, Shepherd L, Rahim A, Jones AF, Bates A. The prevalence of vitamin D abnormalities in South Asians with type 2 diabetes mellitus in the UK. Int J Clin Pract. 2010;64(3):351–5.

    Article  CAS  PubMed  Google Scholar 

  9. Littorin B, Blom P, Scholin A, 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. 2006;49:2847–52.

    Article  CAS  PubMed  Google Scholar 

  10. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.

    Article  CAS  PubMed  Google Scholar 

  11. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398–417.

    Article  PubMed  Google Scholar 

  12. White P, Cooke N. The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab. 2000;11:320–7.

    Article  CAS  PubMed  Google Scholar 

  13. Negri AL. Proximal tubule endocytic apparatus as the specific renal uptake mechanism for vitamin D-binding protein/25-(OH)D3 complex. Nephrology (Carlton). 2006;11:510–5.

    Article  CAS  Google Scholar 

  14. Nykjaer A, Dragun D, Walther D, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999;96:507–15.

    Article  CAS  PubMed  Google Scholar 

  15. Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev. 2005;26:662–87.

    Article  CAS  PubMed  Google Scholar 

  16. Holick MF. Vitamin D: a D-lightful solution for health. J Investig Med. 2011;59:872–80.

    CAS  PubMed  Google Scholar 

  17. Bener A, Alsaied A, Al-Ali M, et al. High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children. Acta Diabetol. 2009;46:183–9.

    Article  CAS  PubMed  Google Scholar 

  18. Janner M, Ballinari P, Mullis PE, Fluck CE. High prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes. Swiss Med Wkly. 2010;140:w13091.

    PubMed  Google Scholar 

  19. Greer RM, Rogers MA, Bowling FG, et al. Australian children and adolescents with type 1 diabetes have low vitamin D levels. Med J Aust. 2007;187:59–60.

    PubMed  Google Scholar 

  20. Thrailkill KM, Jo CH, Cockrell GE, Moreau CS, Fowlkes JL. Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency? J Clin Endocrinol Metab. 2011;96:142–9.

    Article  CAS  PubMed  Google Scholar 

  21. Cooper JD, Smyth DJ, Walker NM, et al. Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes. Diabetes. 2011;60:1624–31.

    Article  CAS  PubMed  Google Scholar 

  22. Bierschenk L, Alexander J, Wasserfall C, Haller M, Schatz D, Atkinson M. Vitamin D levels in subjects with and without type 1 diabetes residing in a solar rich environment. Diabetes Care. 2009;32:1977–9.

    Article  CAS  PubMed  Google Scholar 

  23. Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML. Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001–2004. Pediatrics. 2009;124:e362–70.

    Article  PubMed  Google Scholar 

  24. Simmons JH, Raines M, Ness KD, et al. Metabolic control and bone health in adolescents with type 1 diabetes. Int J Pediatr Endocrinol. 2011;2011:13.

    Article  PubMed  CAS  Google Scholar 

  25. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27:2813–8.

    Article  CAS  PubMed  Google Scholar 

  26. Reis JP, von Muhlen D, Miller ER III, Michos ED, Appel LJ. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics. 2009;124:e371–9.

    Article  PubMed  Google Scholar 

  27. Muscogiuri G, Sorice GP, Prioletta A, et al. 25-Hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in obesity. Obesity (Silver Spring). 2010;18:1906–10.

    Article  CAS  Google Scholar 

  28. Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J. The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res. 2009;29:3713–20.

    CAS  PubMed  Google Scholar 

  29. Blum M, Dolnikowski G, Seyoum E, et al. Vitamin D(3) in fat tissue. Endocrine. 2008;33:90–4.

    Article  CAS  PubMed  Google Scholar 

  30. Devaraj S, Jialal G, Cook T, Siegel D, Jialal I. Low vitamin D levels in Northern American adults with the metabolic syndrome. Horm Metab Res. 2011;43:72–4.

    Article  CAS  PubMed  Google Scholar 

  31. Tahrani AA, Ball A, Shepherd L, Rahim A, Jones AF, Bates A. The prevalence of vitamin D abnormalities in South Asians with type 2 diabetes mellitus in the UK. Int J Clin Pract. 2010;64:351–5.

    Article  CAS  PubMed  Google Scholar 

  32. Al-Daghri NM, Al-Attas OS, Al-Okail MS, et al. Severe hypovitaminosis D is widespread and more common in non-diabetics than diabetics in Saudi adults. Saudi Med J. 2010;31:775–80.

    PubMed  Google Scholar 

  33. Hidayat R, Setiati S, Soewondo P. The association between vitamin D deficiency and type 2 diabetes mellitus in elderly patients. Acta Med Indones. 2010;42:123–9.

    PubMed  Google Scholar 

  34. Parker J, Hashmi O, Dutton D, et al. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. 2010;65:225–36.

    Article  CAS  PubMed  Google Scholar 

  35. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92:2017–29.

    Article  CAS  PubMed  Google Scholar 

  36. Liu J, Tan H, Jeynes B. Serum 25OH vitamin D level, femur length, and risk of type 2 diabetes among adults. Appl Physiol Nutr Metab. 2011;36:264–70.

    Article  CAS  PubMed  Google Scholar 

  37. Grimnes G, Emaus N, Joakimsen RM, et al. Baseline serum 25-hydroxyvitamin D concentrations in the Tromso Study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up. Diabet Med. 2010;27:1107–15.

    Article  CAS  PubMed  Google Scholar 

  38. Gagnon C, Lu ZX, Magliano DJ, et al. Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, obesity and lifestyle study). Diabetes Care. 2011;34:1133–8.

    Article  CAS  PubMed  Google Scholar 

  39. Knekt P, Laaksonen M, Mattila C, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008;19:666–71.

    Article  PubMed  Google Scholar 

  40. Michos ED. Vitamin D deficiency and the risk of incident Type 2 diabetes. Future Cardiol. 2009;5:15–8.

    Article  CAS  PubMed  Google Scholar 

  41. Mattila C, Knekt P, Mannisto S, et al. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care. 2007;30:2569–70.

    Article  CAS  PubMed  Google Scholar 

  42. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990–2000. Diabetes. 2008;57:2619–25.

    Article  CAS  PubMed  Google Scholar 

  43. Kayaniyil S, Retnakaran R, Harris SB, et al. Prospective associations of vitamin D with β-cell function and glycemia: the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort study. Diabetes. 2011;60(11):2947–53.

    Article  CAS  PubMed  Google Scholar 

  44. Borkar VV, Devidayal, Verma S, Bhalla AK. Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes. Pediatr Diabetes. 2010;11:345–50.

    Article  CAS  PubMed  Google Scholar 

  45. Pozzilli P, Manfrini S, Crino A, et al. Low levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes. Horm Metab Res. 2005;37:680–3.

    Article  CAS  PubMed  Google Scholar 

  46. Huynh T, Greer RM, Nyunt O, et al. The association between ketoacidosis and 25(OH)-vitamin D levels at presentation in children with type 1 diabetes mellitus. Pediatr Diabetes. 2009;10:38–43.

    Article  CAS  PubMed  Google Scholar 

  47. Scragg R, Holdaway I, Singh V, Metcalf P, Baker J, Dryson E. Serum 25-hydroxyvitamin D3 levels decreased in impaired glucose tolerance and diabetes mellitus. Diabetes Res Clin Pract. 1995;27:181–8.

    Article  CAS  PubMed  Google Scholar 

  48. Mathieu C, Badenhoop K. Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab. 2005;16:261–6.

    Article  CAS  PubMed  Google Scholar 

  49. Bland R, Markovic D, Hills CE, et al. Expression of 25-hydroxyvitamin D3–1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol. 2004;89–90:121–5.

    Article  PubMed  CAS  Google Scholar 

  50. Johnson JA, Grande JP, Roche PC, Kumar R. Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28 k in human and rat pancreas. Am J Physiol. 1994;267:E356–60.

    CAS  PubMed  Google Scholar 

  51. Ng KY, Ma MT, Leung KK, Leung PS. Vitamin D and vitamin A receptor expression and the proliferative effects of ligand activation of these receptors on the development of pancreatic progenitor cells derived from human fetal pancreas. Stem Cell Rev. 2011;7:53–63.

    Article  CAS  PubMed  Google Scholar 

  52. Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology. 2006;147:5542–8.

    Article  CAS  PubMed  Google Scholar 

  53. Kajikawa M, Ishida H, Fujimoto S, et al. An insulinotropic effect of vitamin D analog with increasing intracellular Ca2 + concentration in pancreatic beta-cells through nongenomic signal transduction. Endocrinology. 1999;140:4706–12.

    Article  CAS  PubMed  Google Scholar 

  54. Danescu LG, Levy S, Levy J. Vitamin D and diabetes mellitus. Endocrine. 2009;35:11–7.

    Article  CAS  PubMed  Google Scholar 

  55. Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209:823–5.

    Article  CAS  PubMed  Google Scholar 

  56. Cade C, Norman AW. Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-deficient rat in vivo. Endocrinology. 1986;119:84–90.

    Article  CAS  PubMed  Google Scholar 

  57. Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J. 2003;17:509–11.

    CAS  PubMed  Google Scholar 

  58. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79:820–5.

    CAS  PubMed  Google Scholar 

  59. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient—a randomised, placebo-controlled trial. Br J Nutr. 2010;103:549–55.

    Article  CAS  Google Scholar 

  60. Pittas AG, Chung M, Trikalinos T, et al. Systematic review: vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010;152:307–14.

    PubMed  Google Scholar 

  61. Avenell A, Cook JA, MacLennan GS, McPherson GC. Vitamin D supplementation and type 2 diabetes: a substudy of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). Age Ageing. 2009;38:606–9.

    Article  PubMed  Google Scholar 

  62. Parekh D, Sarathi V, Shivane VK, Bandgar TR, Menon PS, Shah NS. Pilot study to evaluate the effect of short-term improvement in vitamin D status on glucose tolerance in patients with type 2 diabetes mellitus. Endocr Pract. 2010;16:600–8.

    Article  PubMed  Google Scholar 

  63. Luo C, Wong J, Brown M, Hooper M, Molyneaux L, Yue DK. Hypovitaminosis D in Chinese type 2 diabetes: lack of impact on clinical metabolic status and biomarkers of cellular inflammation. Diab Vasc Dis Res. 2009;6:194–9.

    Article  CAS  PubMed  Google Scholar 

  64. Walter M, Kaupper T, Adler K, Foersch J, Bonifacio E, Ziegler AG. No effect of the 1alpha,25-dihydroxyvitamin D3 on beta-cell residual function and insulin requirement in adults with new-onset type 1 diabetes. Diabetes Care. 2010;33:1443–8.

    Article  CAS  PubMed  Google Scholar 

  65. Bizzarri C, Pitocco D, Napoli N, et al. No protective effect of calcitriol on beta-cell function in recent-onset type 1 diabetes: the IMDIAB XIII trial. Diabetes Care. 2010;33:1962–3.

    Article  CAS  PubMed  Google Scholar 

  66. Martin RJ, McKnight AJ, Patterson CC, Sadlier DM, Maxwell AP. A rare haplotype of the vitamin D receptor gene is protective against diabetic nephropathy. Nephrol Dial Transplant. 2010;25:497–503.

    Article  CAS  PubMed  Google Scholar 

  67. Bucan K, Ivanisevic M, Zemunik T, et al. Retinopathy and nephropathy in type 1 diabetic patients–association with polymorphysms of vitamin D-receptor, TNF, Neuro-D and IL-1 receptor 1 genes. Coll Antropol. 2009;33(Suppl 2):99–105.

    CAS  PubMed  Google Scholar 

  68. Ponsonby AL, Pezic A, Ellis J, 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. Am J Epidemiol. 2008;168:358–65.

    Article  PubMed  Google Scholar 

  69. Ramagopalan SV, Heger A, Berlanga AJ, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010;20:1352–60.

    Article  CAS  PubMed  Google Scholar 

  70. Mimbacas A, Trujillo J, Gascue C, Javiel G, Cardoso H. Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus. Genet Mol Res. 2007;6:534–42.

    CAS  PubMed  Google Scholar 

  71. Boraska V, Skrabic V, Zeggini E, et al. Family-based analysis of vitamin D receptor gene polymorphisms and type 1 diabetes in the population of South Croatia. J Hum Genet. 2008;53:210–4.

    Article  CAS  PubMed  Google Scholar 

  72. Shimada A, Kanazawa Y, Motohashi Y, et al. Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese. J Autoimmun. 2008;30:207–11.

    Article  CAS  PubMed  Google Scholar 

  73. Panierakis C, Goulielmos G, Mamoulakis D, Petraki E, Papavasiliou E, Galanakis E. Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece. Clin Immunol. 2009;133:276–81.

    Article  CAS  PubMed  Google Scholar 

  74. Fassbender WJ, Goertz B, Weismuller K, 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. Horm Metab Res. 2002;34:330–7.

    Article  CAS  PubMed  Google Scholar 

  75. McDermott MF, Ramachandran A, Ogunkolade BW, et al. Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians. Diabetologia. 1997;40:971–5.

    Article  CAS  PubMed  Google Scholar 

  76. Kahles H, Morahan G, Todd JA, Badenhoop K. Association analyses of the vitamin D receptor gene in 1654 families with type I diabetes. Genes Immun. 2009;10(Suppl 1):S60–3.

    Article  CAS  PubMed  Google Scholar 

  77. Lemos MC, Fagulha A, Coutinho E, et al. Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population. Hum Immunol. 2008;69:134–8.

    Article  CAS  PubMed  Google Scholar 

  78. Israni N, Goswami R, Kumar A, Rani R. Interaction of vitamin D receptor with HLA DRB1 0301 in type 1 diabetes patients from North India. PLoS One. 2009;4:e8023.

    Article  PubMed  CAS  Google Scholar 

  79. Bailey R, Cooper JD, Zeitels L, et al. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007;56:2616–21.

    Article  CAS  PubMed  Google Scholar 

  80. Kocabas A, Karaguzel G, Imir N, Yavuzer U, Akcurin S. Effects of vitamin D receptor gene polymorphisms on susceptibility to disease and bone mineral density in Turkish patients with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2010;23:1289–97.

    Article  CAS  PubMed  Google Scholar 

  81. Ortlepp JR, Lauscher J, Hoffmann R, Hanrath P, Joost HG. The vitamin D receptor gene variant is associated with the prevalence of type 2 diabetes mellitus and coronary artery disease. Diabet Med. 2001;18:842–5.

    Article  CAS  PubMed  Google Scholar 

  82. Nosratabadi R, Arababadi MK, Salehabad VA, et al. Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type-2 diabetes. Int J Immunogenet. 2010;37:493–7.

    Article  CAS  PubMed  Google Scholar 

  83. Hitman GA, Mannan N, McDermott MF, et al. Vitamin D receptor gene polymorphisms influence insulin secretion in Bangladeshi Asians. Diabetes. 1998;47:688–90.

    Article  CAS  PubMed  Google Scholar 

  84. Dilmec F, Uzer E, Akkafa F, Kose E, van Kuilenburg AB. Detection of VDR gene ApaI and TaqI polymorphisms in patients with type 2 diabetes mellitus using PCR-RFLP method in a Turkish population. J Diabetes Complications. 2010;24:186–91.

    Article  PubMed  Google Scholar 

  85. Malecki MT, Frey J, Moczulski D, Klupa T, Kozek E, Sieradzki J. Vitamin D receptor gene polymorphisms and association with type 2 diabetes mellitus in a Polish population. Exp Clin Endocrinol Diabetes. 2003;111:505–9.

    Article  CAS  PubMed  Google Scholar 

  86. Bid HK, Konwar R, Aggarwal CG, et al. Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus: a North Indian study. Indian J Med Sci. 2009;63:187–94.

    Article  PubMed  Google Scholar 

  87. Boullu-Sanchis S, Lepretre F, Hedelin G, et al. Type 2 diabetes mellitus: association study of five candidate genes in an Indian population of Guadeloupe, genetic contribution of FABP2 polymorphism. Diabetes Metab. 1999;25:150–6.

    CAS  PubMed  Google Scholar 

  88. Cyganek K, Mirkiewicz-Sieradzka B, Malecki MT, et al. Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients. Acta Diabetol. 2006;43:114–9.

    Article  CAS  PubMed  Google Scholar 

  89. Filus A, Trzmiel A, Kuliczkowska-Plaksej J, et al. Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome. Aging Male. 2008;11:134–9.

    Article  CAS  PubMed  Google Scholar 

  90. Oh JY, Barrett-Connor E. Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the Rancho Bernardo Study. Metabolism. 2002;51:356–9.

    Article  CAS  PubMed  Google Scholar 

  91. Ye WZ, Reis AF, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G. Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol. 2001;145:181–6.

    Article  CAS  PubMed  Google Scholar 

  92. Ma X, Jing Y, Qin W, et al. Vitamin D receptor gene polymorphism and bone mineral density in patients with type 2 diabetes mellitus. Chin Med J (Engl). 2001;114:1213–5.

    CAS  Google Scholar 

  93. de Boer IH, Ioannou GN, Kestenbaum B, Brunzell JD, Weiss NS. 25-Hydroxyvitamin D levels and albuminuria in the Third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis. 2007;50:69–77.

    Article  PubMed  CAS  Google Scholar 

  94. Diaz VA, Mainous AG III, Carek PJ, Wessell AM, Everett CJ. The association of vitamin D deficiency and insufficiency with diabetic nephropathy: implications for health disparities. J Am Board Fam Med. 2009;22:521–7.

    Article  PubMed  Google Scholar 

  95. Joergensen C, Gall MA, Schmedes A, Tarnow L, Parving HH, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care. 2010;33:2238–43.

    Article  PubMed  Google Scholar 

  96. Thrailkill KM, Nimmo T, Bunn RC, et al. Microalbuminuria in type 1 diabetes is associated with enhanced excretion of the endocytic multiligand receptors megalin and cubilin. Diabetes Care. 2009;32:1266–8.

    Article  CAS  PubMed  Google Scholar 

  97. Ward DT, Yau SK, Mee AP, et al. Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes. J Am Soc Nephrol. 2001;12:779–90.

    CAS  PubMed  Google Scholar 

  98. Schneider LE, Schedl HP, McCain T, Haussler MR. Experimental diabetes reduces circulating 1,25-dihydroxyvitamin D in the rat. Science. 1977;196:1452–4.

    Article  CAS  PubMed  Google Scholar 

  99. Verhaeghe J, Suiker AM, Van Bree R, et al. Increased clearance of 1,25(OH)2D3 and tissue-specific responsiveness to 1,25(OH)2D3 in diabetic rats. Am J Physiol. 1993;265:E215–23.

    CAS  PubMed  Google Scholar 

  100. Fowlkes JL, Bunn RC, Cockrell GE, et al. Dysregulation of the intrarenal vitamin D endocytic pathway in a nephropathy-prone mouse model of type 1 diabetes. Exp Diabetes Res. 2011;2011:269378.

    Article  PubMed  CAS  Google Scholar 

  101. Anderson RL, Ternes SB, Strand KA, Rowling MJ. Vitamin D homeostasis is compromised due to increased urinary excretion of the 25-hydroxycholecalciferol-vitamin D-binding protein complex in the Zucker diabetic fatty rat. Am J Physiol Endocrinol Metab. 2010;299:E959–67.

    Article  CAS  PubMed  Google Scholar 

  102. Ishida H, Seino Y, Matsukura S, et al. Diabetic osteopenia and circulating levels of vitamin D metabolites in type 2 (noninsulin-dependent) diabetes. Metabolism. 1985;34:797–801.

    Article  CAS  PubMed  Google Scholar 

  103. Imura H, Seino Y, Ishida H. Osteopenia and circulating levels of vitamin D metabolites in diabetes mellitus. J Nutr Sci Vitaminol (Tokyo). 1985;31(Suppl):S27–32.

    Article  CAS  Google Scholar 

  104. Hampson G, Evans C, Petitt RJ, et al. Bone mineral density, collagen type 1 alpha 1 genotypes and bone turnover in premenopausal women with diabetes mellitus. Diabetologia. 1998;41:1314–20.

    Article  CAS  PubMed  Google Scholar 

  105. Thrailkill KM, Jo CH, Cockrell GE, Moreau CS, Lumpkin CK, Jr., Fowlkes JL. Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes. Osteoporos Int. 2011 [Epub ahead of print]. doi:10.1007/s00198-011-1807-7.

  106. Takeshita N, Mutoh S, Yamaguchi I. Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha-hydroxyvitamin D3 on the osteopenia. Basic Research Group. Life Sci. 1995;56:1095–101.

    Article  CAS  PubMed  Google Scholar 

  107. Takeshita N, Yoshino T, Mutoh S, Yamaguchi I. Possible involvement of vitamin D3-deficiency and relatively enhanced bone resorption in the development of bone loss in streptozotocin-induced diabetic rats. Life Sci. 1994;55:291–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the Martha Ann Pugh Diabetes Research Fund (to K.M.T.), the Arkansas Biosciences Institute (to J.L.F.), and in part by a National Institutes of Health Grant R01DK055653 (to J.L.F.).

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Correspondence to Kathryn M. Thrailkill.

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Thrailkill, K.M., Fowlkes, J.L. The Role of Vitamin D in the Metabolic Homeostasis of Diabetic Bone. Clinic Rev Bone Miner Metab 11, 28–37 (2013). https://doi.org/10.1007/s12018-012-9127-9

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