Vitamin D and diabetes mellitus: Causal or casual association?

  • M. Grammatiki
  • E. Rapti
  • S. Karras
  • R. A. Ajjan
  • Kalliopi Kotsa


The incidence of both type 2 and type 1 diabetes mellitus has been increasing worldwide. Vitamin D deficiency, or the awareness of its prevalence, has also been increasing. Vitamin D may have a role in the pathogenic mechanisms predisposing to type 2 diabetes by modulating insulin resistance and/or pancreatic β-cell function. Vitamin D status or elements involved in its activation or transport may also be involved in the development of type 1 diabetes mellitus through immunomodulatory role . Based on these observations a potential association between vitamin D and diabetes has been hypothesized. In this review we discuss up to date evidence linking vitamin D with the development of diabetes. Moreover, the role of vitamin D supplementation in the prevention of both types of diabetes is analysed together with its role in improving glycemic control in diabetic patients. We also address the potential role of vitamin D deficiency in the development of macro- and microvascular complications in diabetes. Finally, we provide recommendation for Vitamin D therapy in diabetes in view of current evidence and highlight areas for potential future research in this area.


Vitamin D 25-hydroxyvitamin D Diabetes mellitus Type 1 diabetes Type 2 diabetes Diabetes complications 



Type 2 diabetes mellitus


Type 1 diabetes mellitus


Vitamin D receptor


Parathyroid hormone


Glucose transporter-4


Peroxisome proliferator-activated receptor


25-hydroxyvitamin D


Oral glucose tolerance test


Glycated hemoglobin


Vitamin D binding protein

NOD mice

Non obese diabetic mice


Chronic renal failure


Rennin-angiotensin-aldosterone system


Glomerular filtration rate


Diabetic neuropathy


Diabetic retinopathy


Coronary heart disease


Cardiovascular disease


Intima-media thickness


Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Leahy JL. Pathogenesis of type 2 diabetes mellitus. Arch Med Res. 2005;36(3):197–209.PubMedCrossRefGoogle Scholar
  2. 2.
    Atkinson MA, Maclaren NK. The pathogenesis of insulin-dependent diabetes mellitus. Engl J Med. 1995;331:1428–36.Google Scholar
  3. 3.
    Harinarayan CV. Vitamin D, and diabetes mellitus. Hormones. 2014;13(2):163–81.PubMedGoogle Scholar
  4. 4.
    Takiishi T, Gysemans C, Bouillon R, Mathieu C. Vitamin D and diabetes. Rheum Dis Clin North Am. 2012;38(1):179–206.PubMedCrossRefGoogle Scholar
  5. 5.
    Chuang JC, Cha JY, Garmey JC, Mirmira RG, Repa JJ. Research resource: nuclear hormone receptor expression in the endocrine pancreas. Molecular endocrinology. 2008;22(10):2353–63.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Pludowski P, Holick MF, Pilz S, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmunity reviews. 2013;12(10):976–89.PubMedCrossRefGoogle Scholar
  7. 7.
    Fan Y, Futawaka K, Koyama R, et al. Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles. J Biomed Sci. 2016;23(1):56.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Zostautiene I, Jorde R, Schirmer H, et al. Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Tromsø Study. PLoS One. 2015;10(12), e0145359.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Li L, Wu B, Liu JY, Yang LB. Vitamin D receptor gene polymorphisms and type 2 diabetes: a meta-analysis. Archives Med Res. 2013;44(3):235–41.CrossRefGoogle Scholar
  10. 10.
    Pilz S, Kienreich K, Rutters F, et al. Role of vitamin D in the development of insulin resistance and type 2 diabetes. Curr Diab Rep. 2013;13(2):261–70.PubMedCrossRefGoogle Scholar
  11. 11.
    Zhukouskaya VV, Eller-Vainicher C, Shepelkevich AP, Dydyshko Y, Cairoli E, Chiodini I. Bone health in type 1 diabetes: focus on evaluation and treatment in clinical practice. J Endocrinol Invest. 2015;38(9):941–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Chapter 1: Epidemiology of Type 1 Diabetes. Endocrinol Metab Clin North Am. 2010;39(3):481–97.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Chagas CE, Borges MC, Martini LA, Rogero MM. Focus on vitamin D, inflammation and type 2 diabetes. Nutrients. 2012;4:52–67.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology. 2006;147(12):5542–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Maestro B, Campion J, Davila N, Calle C. Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J. 2000;47:383–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Wright DC, Hucker KA, Holloszy JO, Han DH. Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions. Diabetes. 2004;53:330–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Draznin B, Sussman K, Kao M, Lewis D, Sherman N. The existence of an optimal range of cytosolic free calcium for insulin-stimulated glucose transport in rat adipocytes. J Biol Chem. 1987;262:14385–8.PubMedGoogle Scholar
  18. 18.
    Draznin B. Cytosolic calcium and insulin resistance. Am J Kidney Dis. 1993;21:32–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Reusch JE, Begum N, Sussman KE, Draznin B. Regulation of GLUT-4 phosphorylation by intracellular calcium in adipocytes. Endocrinology. 1991;129:3269–73.PubMedCrossRefGoogle Scholar
  20. 20.
    Dunlop TW, Väisänen S, Frank C, Molnár F, Sinkkonen L, Carl-berg C. The human peroxisome proliferator-activated receptor delta gene is a primary target of 1alpha,25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol. 2005;349:248–60.PubMedCrossRefGoogle Scholar
  21. 21.
    Cade C, Norman AW. Rapid normalization/stimulation by 1,25-dihydroxyvitamin D3 of insulin secretion and glucose tolerance in the Vitamin D-deficient rat. Endocrinology. 1987;120:1490–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Johnson JA, Grande JP, Roche PC, Kumar R. Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28k in human and rat pancreas. Am J Physiol. 1994;267:E356–60.PubMedGoogle Scholar
  23. 23.
    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.PubMedCrossRefGoogle Scholar
  24. 24.
    Maestro B, Davila N, Carranza MC, Calle C. Identification of a Vitamin D response element in the human insulin receptor gene promoter. J Steroid Biochem Mol Biol. 2003;84:223–30.PubMedCrossRefGoogle Scholar
  25. 25.
    Maestro B, Molero S, Bajo S, Davila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct. 2002;20:227–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Bourlon PM, Billaudel B, Faure-Dussert A. Influence of vitamin D3 deficiency and 1,25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas. J Endocrinol. 1999;160:87–95.PubMedCrossRefGoogle Scholar
  27. 27.
    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;17:509–51.PubMedGoogle Scholar
  28. 28.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286:327–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004;53:693–700.PubMedCrossRefGoogle Scholar
  31. 31.
    Chih-Chien S, Min-Tser L, Kuo-Cheng L, Chia-Chao W. Role of Vitamin D in Insulin Resistance. J Biomed Biotechnol. 2012;2012:634195.Google Scholar
  32. 32.
    Pittas AG, Joseph NA, Greenberg AS. Adipocytokines and insulin resistance. J Clin Endocrinol Metab. 2004;89:447–52.PubMedCrossRefGoogle Scholar
  33. 33.
    Christakos S, Liu Y. Biological actions and mechanism of action of calbindin in the process of apoptosis. J Steroid Biochem Mol Biol. 2004;89-90(1–5):401–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209(4458):823–5.PubMedCrossRefGoogle Scholar
  35. 35.
    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(5):820–5.PubMedGoogle Scholar
  36. 36.
    Hyppönen E, Boucher BJ, Berry DJ, Power C. 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes. 2008;57(2):298–305.PubMedCrossRefGoogle Scholar
  37. 37.
    Lu L, Yu Z, Pan A, et al. Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals. Diabetes Care. 2009;32(7):1278–83.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Scragg R, Sowers M. Bell C; Third National Health and Nutrition Examination Survey. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27(12):2813–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Reis JP, von Muhlen D, Kritz-Silverstein D, et al. Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care. 2007;30:1549–55.PubMedCrossRefGoogle Scholar
  40. 40.
    Afzal S, Bojesen SE, Nordestgaard BG. Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem. 2013;52(2):381–91.CrossRefGoogle Scholar
  41. 41.
    Anderson JL, May HT, Horne BD, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106:963–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Forouhi NG, Ye Z, Rickard AP, et al. Circulating 25- hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies. Diabetologia. 2012;55:2173–82.PubMedCrossRefGoogle Scholar
  43. 43.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Gonzalez-MoleroI R-MG, Morcillo S, et al. Vitamin D and incidence of diabetes: a prospective cohort study. Clin Nutr. 2012;31:571–3.CrossRefGoogle Scholar
  45. 45.
    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.PubMedCrossRefGoogle Scholar
  46. 46.
    Hurskainen AR, Virtanen JK, Tuomainen TP, Nurmi T, Voutilainen S. Association of serum 25-hydroxyvitamin D with type 2 diabetes and markers of insulin resistance in a general older population in Finland. Diabetes Metab Res Rev. 2012;28:418–23.PubMedCrossRefGoogle Scholar
  47. 47.
    Husemoen LL, Thuesen BH. Fenger M, Jørgensen T, Glu ̈mer C, Svensson J, et al. Serum 25(OH)D and type 2 diabetes association in a general population. Diabetes Care. 2012;35:1695–700.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Knekt P, Laaksonen M, Mattila C, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008;19:666–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Pilz S, van den Hurk K, Nijpels G, et al. Vitamin D status, incident diabetes and prospective changes in glucose metabolism in older subjects: the Hoorn study. Nutr Metab Cardiovasc Dis. 2012;22:883–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Pittas AG, Sun Q, Manson JE, Dawson-Hughes B, Hu FB. Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in women. Diabetes Care. 2010;33:2021–3.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Robinson JG, Manson JE, Larson J, et al. Lack of association between 25(OH)D levels and incident type 2 diabetes in older women. Diabetes Care. 2011;34:628–34.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Thorand B, Zierer A, Huth C, et al. Effect of serum 25- hydroxyvitamin D on risk for type 2 diabetes may be partially mediated by subclinical inflammation: results from the MONICA/KORA Augsburg study. Diabetes Care. 2011;34:2320–2.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Deleskog A, Hilding A, Brismar K, Hamsten A, Efendic S, Ostenson CG. Low serum 25- hydroxyvitamin D level predicts progression to type 2 diabetes in individuals with prediabetes but not with normal glucose tolerance. Diabetologia. 2012;55:1668–78.PubMedCrossRefGoogle Scholar
  54. 54.
    Pittas AG, Harris SS, Stark PC, et al. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007;30:980–6.PubMedCrossRefGoogle Scholar
  55. 55.
    de Boer IH, Tinker LF, Connelly S, et al. Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women’s Health Initiative. Diabetes Care. 2008;31:701–7.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Avenell A, Cook JA, MacLennan GS, et al. 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.PubMedCrossRefGoogle Scholar
  57. 57.
    Zittermann A, Frisch S, Berthold HK, et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr. 2009;89:1321–7.PubMedCrossRefGoogle Scholar
  58. 58.
    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.CrossRefGoogle Scholar
  59. 59.
    Jorde R, Sneve M, Torjesen P, et al. No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year. J Intern Med. 2010;267:462–72.PubMedCrossRefGoogle Scholar
  60. 60.
    Wood AD, Secombes KR, Thies F, et al. Vitamin D3 Supplementation Has No Effect on Conventional Cardiovascular Risk Factors: A Parallel-Group, Double-Blind, Placebo-Controlled RCT. J Clin Endocrinol Metab. 2012;97:3557–68.PubMedCrossRefGoogle Scholar
  61. 61.
    Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med. 2009;26:19–27.PubMedCrossRefGoogle Scholar
  62. 62.
    Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403.PubMedCrossRefGoogle Scholar
  63. 63.
    Mitri J, Dawson-Hughes B, Hu FB, et al. Effects of vitamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Am J Clin Nutr. 2011;94:486–94.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Nazarian S, St Peter JV, Boston RC, et al. Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose. Transl Res. 2011;158:276–81.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Jorde R, Sollid ST, Svartberg J, et al. Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. J Clin Endocrinol Metab. 2016;101(4):1647–55.PubMedCrossRefGoogle Scholar
  66. 66.
    Tuomainen TP, Virtanen JK, Voutilainen S, Nurmi T, Mursu J, de Mello VD, et al. Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study. J Diabetes Res. 2015;2015:672653.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Barengolts E, Manickam B, Eisenberg Y, Akbar A, Kukreja S, Ciubotaru I. Effect of high-dose vitamin D repletion on glycemic control in African-American males with prediabetes and hypovitaminosis D. Endocr Pract. 2015;21(6):604–12.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Oosterwerff MM, Eekhoff EM, Van Schoor NM, et al. Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D–deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial. Am J Clin Nutr. 2014;100(1):152–60.PubMedCrossRefGoogle Scholar
  69. 69.
    Davidson MB, Duran P, Lee ML, Friedman TC. High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D. Diabetes Care. 2013;36(2):260–6.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Poolspup N, Suksomboon N, Plordplong N. Effect of vitamin D supplementation on insulin resistance and glycaemic control in prediabetes: a systematic review and meta-analysis. Diabet Med. 2016;33(3):290–9.CrossRefGoogle Scholar
  71. 71.
    Seida JC, Mitri J, Colmers IN, et al. Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):3551–60.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Sorkin JD, Vasaitis TS, Streeten E, Ryan AS, Goldberg AP. Evidence for threshold effects of 25-hydroxyvitamin D on glucose tolerance and insulin resistance in black and white obese postmenopausal women. J Nutr. 2014;144:734–42.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Pittas AG, Dawson-Hughes B, Sheehan PR, et al. D2d Research Group. Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial. Diabetes Care. 2014;37(12):3227–34.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Krul-Poel YH, Westra S, ten Boekel E, et al. Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial. Diabetes Care. 2015;38(8):1420–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Hewison M. An update on vitaminDandhuman immunity. Clin Endocrinol. 2012;76:315–25.CrossRefGoogle Scholar
  76. 76.
    Olt S. Relationship between vitamin D and glycemic control in patients with type 2 diabetes mellitus. Int J Clin Exp Med. 2015;8(10):19180–3.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Kostoglou-Athanassiou I, Athanassiou P, Gkountouvas A, Kaldrymides P. Vitamin D and glycemic control in diabetes mellitus type 2. Ther Adv Endocrinol Metab. 2013;4(4):122–8.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Orwoll E, Riddle M, Prince M. Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus. Am J Clin Nutr. 1994;59(5):1083–7.PubMedGoogle Scholar
  79. 79.
    Talaei A, Mohamadi M, Adgi Z. The effect of vitamin D on insulin resistance in patients with type 2 diabetes. Diabetol Metab Syndr. 2013;5:8.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    George PS, Pearson ER, Witham MD. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta-analysis. Diabet Med. 2012;29(8):e142–50.PubMedCrossRefGoogle Scholar
  81. 81.
    Krul-Poel YH, Ter Wee M, Lips P, Simsek S. MANAGEMENT OF ENDOCRINE DISEASE: The effect of vitamin D supplementation on glycaemic control in patients with Type 2 Diabetes Mellitus: a systematic review and meta-analysis. Eur J Endocrinol. 2016.Google Scholar
  82. 82.
    Bellastella G, Maiorino MI, Olita L, et al. Vitamin D deficiency in type 2 diabetic patients with hypogonadism. J Sex Med. 2014;11:536–42.PubMedCrossRefGoogle Scholar
  83. 83.
    Ibrahim MA, Sarhan II, Halawa MR, et al. Study of the effect of vitamin D supplementation on glycemic control in type 2 diabetic prevalent hemodialysis patients. Hemodial Int. 2015;19 Suppl 3:S11–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Perez-Diaz I, Sebastian-Barajas G, Hernandez-Flores ZG, Rivera-Moscoso R, Osorio-Landa HK, Flores-Rebollar A. The impact of vitamin D levels on glycemic control and bone mineral density in postmenopausal women with type 2 diabetes. J Endocrinol Invest. 2015;38(12):1365–72.PubMedCrossRefGoogle Scholar
  85. 85.
    Shaseb E, Tohidi M, Abbasinazari M, et al. The effect of a single dose of vitamin D on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: a randomized clinical trial. Acta Diabetol. 2016;53(4):575–82.PubMedCrossRefGoogle Scholar
  86. 86.
    Steck AK, Rewers MJ. Genetics of type 1 diabetes. Clin Chem. 2011;57(2):176–85.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Ogunkolade BW, Boucher BJ, Prahl JM, 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. 2002;51(7):2294–300.PubMedCrossRefGoogle Scholar
  88. 88.
    Garcia D, Angel B, Carrasco E, et al. VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago. Chile Diabetes Res Clin Pract. 2007;77(1):134–40.PubMedCrossRefGoogle Scholar
  89. 89.
    Pani MA, Knapp M, Donner H, et al. Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Diabetes. 2000;49(3):504–7.PubMedCrossRefGoogle Scholar
  90. 90.
    Chang TJ, Lei HH, Yeh JI, et al. Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population. Clin Endocrinol (Oxf). 2000;52(5):575–80.CrossRefGoogle Scholar
  91. 91.
    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(2):134–8.PubMedCrossRefGoogle Scholar
  92. 92.
    Turpeinen H, Hermann R, Vaara S, et al. Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population. Eur J Endocrinol. 2003;149(6):591–6.PubMedCrossRefGoogle Scholar
  93. 93.
    Tizaoui K, Kaabachi W, Hamzaoui A, Hamzaoui K. Contribution of VDR polymorphisms to type 1 diabetes susceptibility: Systematic review of case–control studies and meta-analysis. J Steroid Biochem Mol Biol. 2014;143:240–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Ongagna JC, Pinget M, Belcourt A. Vitamin D-binding protein gene polymorphism association with IA-2 autoantibodies in type 1 diabetes. Clin Biochem. 2005;38(5):415–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Ongagna JC, Kaltenbacher MC, Sapin R, Pinget M, Belcourt A. The HLA-DQB alleles and amino acid variants of the vitamin Dbinding protein in diabetic patients in Alsace. Clin Biochem. 2001;34:59–63.PubMedCrossRefGoogle Scholar
  96. 96.
    Thorsen SU, Mortensen HB, Carstensen B, et al. No association between type 1 diabetes and genetic variation in vitamin D metabolism genes: a Danish study. Pediatr Diabetes. 2014;15(6):416–21.PubMedCrossRefGoogle Scholar
  97. 97.
    Blanton D, Han Z, Bierschenk L, et al. Reduced serum vitamin D binding protein levels are associated with type 1 diabetes. Diabetes. 2011;60:2566–70.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Hussein AG, Mohamed RH, Alghobashy AA. Synergism of CYP2R1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Cell Immunol. 2012;279(1):42–5.PubMedCrossRefGoogle Scholar
  99. 99.
    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(5):1624–31.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Ramos-Lopez E, Brück P, Jansen T, Herwig J, Badenhoop K. CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans. Diabetes Metab Res Rev. 2007;23(8):631–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Bailey R, Cooper JD, Zeitels L, et al. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007;56(10):2616–21.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Frederiksen BN, Kroehl M, Fingerlin TE, Steck AK, Rewers M, Norris JM. Association between vitamin D metabolism gene polymorphisms and risk of islet autoimmunity and progression to type 1 diabetes: the diabetes autoimmunity study in the young (DAISY). J Clin Endocrinol Metab. 2013;98(11):E1845–51.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Pociot F, McDermott MF. Genetics of type 1 diabetes mellitus. Genes Immun. 2002;3(5):235–49.PubMedCrossRefGoogle Scholar
  104. 104.
    Liu YJ. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol. 2005;23:275–306.PubMedCrossRefGoogle Scholar
  105. 105.
    Guery JC, Adorini L. Dendritic cells are the most efficient in presenting endogenous naturally processed self-epitopes to class II-restricted T cells. J Immunol. 1995;54:536–44.Google Scholar
  106. 106.
    Yang CY, Leung PS, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45:217–26.PubMedCrossRefGoogle Scholar
  107. 107.
    Overbergh L, Decallonne B, Waer M, et al. 1alpha,25-dihydroxyvitamin D3 induces an autoantigen specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543). Diabetes. 2009;49:1301–7.CrossRefGoogle Scholar
  108. 108.
    Riachy R, Vandewalle B, Moerman E, et al. 1,25-Dihydroxyvitamin D3 protects human pancreatic islets against cytokine-induced apoptosis via down-regulation of the Fas receptor. Apoptosis. 2006;11:151–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Casteels K, Waer M, Laureys J, et al. Prevention of autoimmune destruction of syngeneic islet grafts in spontaneously diabetic nonobese diabetic mice by a combination of a vitamin D3 analog and cyclosporine. Diabetes. 1998;51:1367–74.Google Scholar
  110. 110.
    Del Pino-Montes J, Benito GE, Fernandez-Salazar MP, et al. Calcitriol improves streptozotocin-induced diabetes and recovers bone mineral density in diabetic rats. Calcif Tissue Int. 2004;75:526–32.PubMedCrossRefGoogle Scholar
  111. 111.
    Takiishi T, Belle TV, Gysemans C, Mathieu C. Effects of vitamin D on antigen-specific and non-antigen-specific immune modulation: relevance for type 1 diabetes. Pediat Diabetes. 2013;14:81–9.CrossRefGoogle Scholar
  112. 112.
    Luong KVQ, Hoang Nguyen LT, Pham Nguyen DN. The role of vitamin D in protecting type 1 diabetes mellitus. Diabetes Metab Res Rev. 2005;21:338–46.PubMedCrossRefGoogle Scholar
  113. 113.
    Keen H, Ekoe JM. The geography of diabetes mellitus. Br Med Bull. 1984;40:359–65.PubMedCrossRefGoogle Scholar
  114. 114.
    Mathieu C, Waer M, Laureys J, et al. Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia. 1994;37:552–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358(9292):1500–3.PubMedCrossRefGoogle Scholar
  116. 116.
    Dong JY, Zhang WG, Chen JJ, Zhang ZL, Han SF, Qin LQ. Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies. Nutrients. 2013;5(9):3551–62.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Mutlu A, Mutlu GY, Ozsu E, Cizmecioglu FM, Hatun S. Vitamin D deficiency in children and adolescents with type 1 diabetes. J Clin Res Pediatr Endocrinol. 2011;3:179–83.PubMedPubMedCentralGoogle Scholar
  118. 118.
    Shen L, Zhuang QS, Ji HF. Assessment of vitamin D levels in type 1 and type 2 diabetes patients: Results from metaanalysis. Mol Nutr Food Res. 2016;60(5):1059–67.PubMedCrossRefGoogle Scholar
  119. 119.
    Rasoul MA, Al-Mahdi M, Al-Kandari H, Dhaunsi GS, Haider MZ. Low serum vitamin-D status is associated with high prevalence and early onset of type-1 diabetes mellitus in Kuwaiti children. BMC Pediatr. 2016;16(1):95.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Raab J, Giannopoulou EZ, Schneider S, et al. Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression. Diabetologia. 2014;57(5):902–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Al-Daghri NM, Al-Attas OS, Alokail MS, et al. Lower vitamin D status is more common among Saudi adults with diabetes mellitus type 1 than in non-diabetics. BMC Public Health. 2014;14:153.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Abd-Allah SH, Pasha HF, Hagrass HA, Alghobashy AA. Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Gene. 2014;536(2):430–4.PubMedCrossRefGoogle Scholar
  123. 123.
    Greer RM, Portelli SL, Hung BS, et al. Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes. Pediatr Diabetes. 2013;14(1):31–41.PubMedCrossRefGoogle Scholar
  124. 124.
    Thorsen SU, Mortensen HB, Carstensen B, et al. No difference in vitamin D levels between children newly diagnosed with type 1 diabetes and their healthy siblings: a 13-year nationwide Danish study. Diabetes Care. 2013;36(9):e157–8.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Sørensen IM, Joner G, Jenum PA, Eskild A, Torjesen PA, Stene LC. Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring. Diabetes. 2012;61(1):175–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Sørensen IM, Joner G, Jenum PA, et al. Vitamin D-binding protein and 25-hydroxyvitamin D during pregnancy in mothers whose children later developed type 1 diabetes. Diabetes Metab Res Rev. 2016. doi: 10.1002/dmrr.2812.Google Scholar
  127. 127.
    Miettinen ME, Reinert L, Kinnunen L, et al. Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring. Diabetologia. 2012;55(5):1291–4.PubMedCrossRefGoogle Scholar
  128. 128.
    Jia-Yi D, Weiguo Z, Jiong Jack C, Zeng-Li Z, Shu-Fen H, Li-Qiang Q. Vitamin D Intake and Risk of Type 1 Diabetes: A Meta-Analysis of Observational Studies. Nutrients. 2013;5:3551–62.CrossRefGoogle Scholar
  129. 129.
    The EURODIAB Substudy 2 Study Group. Vitamin D supplement in early childhood and risk fortype I (insulin-dependent) diabetes mellitus. Diabetologia. 1999;42:51–4.CrossRefGoogle Scholar
  130. 130.
    Stene LC, Ulriksen J, Magnus P, Joner G. Use of cod liver oil during pregnancy associated with lower risk of type I diabetes in the offspring. Diabetologia. 2000;43:1093–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Stene LC, Joner G. 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. Am J Clin Nutr. 2003;78:1128–34.PubMedGoogle Scholar
  132. 132.
    Visalli N, Sebastiani L, Adorisio E, et al. IMDIAB Group. Environmental risk factors for type 1 diabetes in Rome and province. Arch. Dis. Child. 2003;88:695–8.Google Scholar
  133. 133.
    Tenconi MT, Devoti G, Comelli M, et al. Pavia T1DM Registry Group. Major childhood infectious diseases and other determinants associated with type 1 diabetes: A case–control study. Acta Diabetol. 2007;44:14–9.PubMedCrossRefGoogle Scholar
  134. 134.
    Ahadi M, Tabatabaeiyan M, Moazzami K. Association between environmental factors and risk of type 1 diabetes—A case–control study. Endokrynol Pol. 2011;62:134–7.PubMedGoogle Scholar
  135. 135.
    Simpson M, Brady H, Yin X, et al. No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: The Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia. 2011;54:2779–88.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Marjamaki L, Niinisto S, Kenward MG, et al. Maternal intake of vitamin D during pregnancy and risk of advanced β cell autoimmunity and type 1 diabetes in offspring. Diabetologia. 2010;53:1599–607.PubMedCrossRefGoogle Scholar
  137. 137.
    Al Sawah S, Compher CW, Hanlon AL, Lipman TH. 25-Hydroxyvitamin D and glycemic control: A cross-sectional study of children and adolescents with type 1 diabetes. Diabetes Res Clin Pract. 2016;115:54–9.PubMedCrossRefGoogle Scholar
  138. 138.
    Lamichhane AP, Crandell JL, Jaacks LM, Couch SC, Lawrence JM, Mayer-Davis EJ. Longitudinal associations of nutritional factors with glycated hemoglobin in youth with type 1 diabetes: the SEARCH Nutrition Ancillary Study. Am J Clin Nutr. 2015;101(6):1278–85.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Aljabri KS, Bokhari SA, Khan MJ. Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency. Ann Saudi Med. 2010;30(6):454–8.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Mohammadian S, Fatahi N, Zaeri H, Vakili MA. Effect of Vitamin D3 Supplement in Glycemic Control of Pediatrics with Type 1 Diabetes Mellitus and Vitamin D Deficiency. J Clin Diagn Res. 2015;9(3):SC05–7.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Shih EM, Mittelman S, Pitukcheewanont P, Azen CG, Monzavi R. Effects of vitamin d repletion on glycemic control and inflammatory cytokines in adolescents with type 1 diabetes. Pediat Diabetes. 2016;17:36–43.CrossRefGoogle Scholar
  142. 142.
    Nwosu BU, Maranda L. The effects of vitamin D supplementation on hepatic dysfunction, vitamin D status, and glycemic control in children and adolescents with vitamin D deficiency and either type 1 or type 2 diabetes mellitus. PLoS One. 2014;9(6), e99646.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Herrmann M, Sullivan DR, Veillard AS, et al. The FIELD Study Investigators. Serum 25-Hydroxyvitamin D: A Predictor of Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes. Diabetes Care. 2015;38:521–8.PubMedCrossRefGoogle Scholar
  144. 144.
    Remuzzi G, Schieppati A, Ruggenenti P. Clinical practice. Nephropathy in patients with type 2 diabetes. N Engl J Med. 2002;346:1145–51.PubMedCrossRefGoogle Scholar
  145. 145.
    Deng X, Cheng J, Shen M. Vitamin D improves diabetic nephropathy in rats by inhibiting renin and relieving oxidative stress. J Endocrinol Invest. 2016;39(6):657–66.PubMedCrossRefGoogle Scholar
  146. 146.
    Izquierdo MJ, Cavia M, Muρiz P, et al. Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients. BMC Nephrol. 2012;13:159.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Li YC. Podocytes as target of vitamin D. Curr Diabetes Rev. 2011;7:35–40.PubMedCrossRefGoogle Scholar
  148. 148.
    Yuan W, Pan W, Kong J, et al. 1,25-Dihydroxyvitamin D3 Suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem. 2007;282:29821–30.PubMedCrossRefGoogle Scholar
  149. 149.
    Parving HH, Lehnert H, Brφchner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870–8.PubMedCrossRefGoogle Scholar
  150. 150.
    Agarwal R, Acharya M, Tian J, et al. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int. 2005;68:2823–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Alborzi P, Patel NA, Peterson C, et al. Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: a randomized double-blind pilot trial. Hypertension. 2008;52:249–55.PubMedCrossRefGoogle Scholar
  152. 152.
    de Boer IH, Sachs MC, Cleary PA, et al. Diabetes Control and Complication Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group. Circulating vitamin D metabolites and kidney disease in type 1 diabetes. J Clin Endocrinol Metab. 2012;97(12):4780–8.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Joergensen C, Tarnow L, Goetze JP. Vitamin D analogue therapy, cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy: a randomized trial. Diabet Med. 2015;32(3):374–81.PubMedCrossRefGoogle Scholar
  154. 154.
    de Zeeuw D, Agarwal R, Amdahl M, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet. 2010;376:1543–51.PubMedCrossRefGoogle Scholar
  155. 155.
    Derakhshanian H, Shab-Bidar S, Speakman JR, Nadimi H, Djafarian K. Vitamin D and diabetic nephropathy: a systematic review and meta-analysis. Nutrition. 2015;31:1189–94.PubMedCrossRefGoogle Scholar
  156. 156.
    National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health. Diabetic neuropathies: the nerve damage of diabetes Bethesda. National Institutes of Health, The U.S. Department of Health and Human Services; 2009, Available from: h [updated June 25, 2012].
  157. 157.
    Tesfaye S, Boulton AJ, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285–93.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Esyeghamati A, Fotouhi A, Faghihi-Kashani S, et al. Non-linear contribution of serum vitamin D to symptomatic diabetic neuropathy: A case–control study. Diabetes Res Clin Pract. 2016;111:44–50.CrossRefGoogle Scholar
  159. 159.
    Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005;29:21–30.PubMedCrossRefGoogle Scholar
  160. 160.
    Naveilhan P, Neveu I, Wion D, Brachet P. 1,25- Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. NeuroReport. 1996;7(13):2171–5. v1996.PubMedCrossRefGoogle Scholar
  161. 161.
    Ahmadieh H, Azar ST, Lakkis N, Arabi A. Hypovitaminosis d in patients with type 2 diabetes mellitus: a relation to disease control and complications. ISRN Endocrinol. 2013;2013:641098.PubMedPubMedCentralGoogle Scholar
  162. 162.
    Shehab D, Al-Jarallah K, Mojiminiyi OA, Al Mohamedy H, Abdella NA. Does Vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes? Diabet Med. 2012;29:43–9.PubMedCrossRefGoogle Scholar
  163. 163.
    Soderstrom LH, Johnson SP, Diaz VA, Mainous 3rd AG. Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001–2004 NHANES. Diabet Med. 2012;29:50–5.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Shehab D, Al-Jarallah K, Abdella N, Mojiminiyi OA, Al Mohamedy H. Prospective evaluation of the effect of short-term oral vitamin d supplementation on peripheral neuropathy in type 2 diabetes mellitus. Med Princ Pract. 2015;24:250–6.PubMedCrossRefGoogle Scholar
  165. 165.
    Lee P, Chen R. Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain. Arch Intern Med. 2008;168(7):171–2.CrossRefGoogle Scholar
  166. 166.
    Van Belle TL, Gysemans C, Mathieu C. Vitamin D and diabetes: the odd couple. Trends Endocrinol Metab. 2013;24:561–8.PubMedCrossRefGoogle Scholar
  167. 167.
    Verrotti A, Loiacono G, Mohn A, Chiarelli F. New insights in diabetic autonomic neuropathy in children and adolescents. Eur J Endocrinol. 2009;161:811–8.PubMedCrossRefGoogle Scholar
  168. 168.
    Lv WS, Zhao WJ, Gong SL, et al. Serum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis. J Endocrinol Invest. 2015;38(5):513–8.PubMedCrossRefGoogle Scholar
  169. 169.
    Bell DS. Reversal of the Symptoms of Diabetic Neuropathy through Correction of Vitamin D Deficiency in a Type 1 Diabetic Patient. Case Rep Endocrinol. 2012;2012:165056.PubMedPubMedCentralGoogle Scholar
  170. 170.
    Yau JW, Rogers SL, Kawasaki R, et al. Meta-analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors ofdiabetic retinopathy. Diabetes Care. 2012;35(3):556–64.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Bonakdaran S, Shoeibi N. Is there any correlation between vitamin D insufficiency and diabetic retinopathy? Int J Ophthalmol. 2015;8(2):326–31.PubMedPubMedCentralGoogle Scholar
  172. 172.
    Albert DM, Scheef EA, Wang S, et al. Calcitriol is a potent inhibitor of retinal neovascularization. Invest Ophthalmol Vis Sci. 2007;48:2327–34.PubMedCrossRefGoogle Scholar
  173. 173.
    Ren Z, Li W, Zhao Q, Ma L, Zhu J. The impact of 1,25- dihydroxy vitamin D3 on the expressions of vascular endothelial growth factor and transforming growth factor-b1 in the retinas of rats with diabetes. Diabetes Res Clin Pract. 2012;98:474–80.PubMedCrossRefGoogle Scholar
  174. 174.
    Shokravi MT, Marcus DM, Alroy J, Egan K, Saornil MA, Albert DM. Vitamin D inhibits angiogenesis in transgenic murineretinoblastoma. Invest Ophthalmol Vis Sci. 1995;36:83–7.PubMedGoogle Scholar
  175. 175.
    Kaur H, Donaghue KC, Chan AK, et al. Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes. Diabetes Care. 2011;34(6):1400–2.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Shimo N, Yasuda T, Kaneto H, et al. Vitamin D deficiency is significantly associated with retinopathy in young Japanese type 1 diabetic patients. Diabetes Res Clin Pract. 2014;106(2):e41–3.PubMedCrossRefGoogle Scholar
  177. 177.
    Alcubierre N, Valls J, Rubinat E, et al. Vitamin D Deficiency Is Associated with the Presence and Severity of Diabetic Retinopathy in Type 2 Diabetes Mellitus. J Diabetes Res. 2015;2015:374178.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Alam U, Amjad Y, Chan AW, Asghar O, Petropoulos IN, Malik RA. Vitamin D Deficiency Is Not Associated with Diabetic Retinopathy or Maculopathy. J Diabetes Res. 2016;2016:6156217.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Taverna MJ, Selam JL, Slama G. Association between a protein polymorphism in the start codon of the vitamin D receptor gene and severe diabetic retinopathy in C-peptide- negative type 1 diabetes. J Clin Endocrinol Metab. 2005;90:4803–8.PubMedCrossRefGoogle Scholar
  180. 180.
    Taverna MJ, Sola A, Guyot-Argenton C, et al. Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy. Diabetologia. 2002;45:436–42.PubMedCrossRefGoogle Scholar
  181. 181.
    Reddy GB, Sivaprasad M, Shalini T, et al. Plasma vitamin D status in patients with type 2 diabetes with and without retinopathy. Nutrition. 2015;31(7–8):959–63.PubMedCrossRefGoogle Scholar
  182. 182.
    Zoppini G, Galletti A, Targher G, et al. Lower levels of 25-hydroxyvitamin D3 are associated with a higher prevalence of microvascular complications in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2015;3(1), e000058.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    He R, Shen J, Liu F, et al. Vitamin D deficiency increases the risk of retinopathy in Chinese patients with type 2 diabetes. Diabet Med. 2014;31(12):1657–64.PubMedCrossRefGoogle Scholar
  184. 184.
    Patrick PA, Visintainer PF, Shi Q, Weiss IA, Brand DA. Vitamin D and retinopathy in adults with diabetes mellitus. Arch Ophthalmol. 2012;130(6):756–60.PubMedCrossRefGoogle Scholar
  185. 185.
    Aksoy H, AkcΈay F, Kurtul N, Baykal O, Avci B. Serum 1,25 dihydroxy vitamin D (1,25(OH)2D3), 25 hydroxy vitamin D(25(OH)D) and parathormone levels in diabetic retinopathy. Clin Biochem. 2000;33(1):47–51.PubMedCrossRefGoogle Scholar
  186. 186.
    Suzuki A, Kotake M, Ono Y, et al. Hypovitaminosis D in type 2 diabetesmellitus: associationwith microvascular complications and type of treatment. Endocr J. 2006;53(4):503–10.PubMedCrossRefGoogle Scholar
  187. 187.
    Payne JF, Ray R, Watson DG, et al. Vitamin D insufficiency in diabetic retinopathy. Endocr Pract. 2012;18(2):185–93.PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Zhong X, Du Y, Lei Y, Liu N, Guo Y, Pan T. Effects of vitamin D receptor gene polymorphism and clinical characteristics on risk of diabetic retinopathy in Han Chinese type 2 diabetes patients. Gene. 2015;566(2):212–6.PubMedCrossRefGoogle Scholar
  189. 189.
    Hong YJ, Kang ES, Ji MJ, et al. Association between Bsm1 Polymorphism in Vitamin D Receptor Gene and Diabetic Retinopathy of Type 2 Diabetes in Korean Population. Endocrinol Metab (Seoul). 2015;30(4):469–74.CrossRefGoogle Scholar
  190. 190.
    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.PubMedCrossRefGoogle Scholar
  191. 191.
    Hao Y, Ma X, Luo Y, et al. Additional role of serum 25- hydroxyvitamin D3 levels in atherosclerosis in Chinese middleaged and elderly men. Clin Exp Pharmacol Physiol. 2014;41(3):174–9.PubMedCrossRefGoogle Scholar
  192. 192.
    Papandreou D, Hamid ZT. The Role of Vitamin D in Diabetes and Cardiovascular Disease: An Updated Review of the Literature. Dis Markers. 2015;2015:580474.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Heidari B, Nargesi AA, Hafezi-Nejad N, et al. Assessment of serum 25 hydroxy vitamin D improves coronary heart disease risk stratification in patients withtype 2 diabetes. Am Heart J. 2015;170(3):573–9.e5.PubMedCrossRefGoogle Scholar
  194. 194.
    Kunadian V, Ford GA, Bawamia B, et al. Vitamin D deficiency and coronary artery disease: a review of the evidence. Am Heart J. 2014;167(3):283–91.PubMedCrossRefGoogle Scholar
  195. 195.
    Lee JH, Gadi R, Spertus JA, et al. Prevalence of vitamin D deficiency in patients with acute myocardial infarction. Am J Cardiol. 2011;107(11):1636–8.PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Schneider L, Lutsey PL, Selvin E, et al. Vitamin D, vitamin D binding protein gene polymorphisms, race and risk of incident stroke: the Atherosclerosis Risk in Communities (ARIC) study. Eur J Neurol. 2015;22(8):1220–7.PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Kendrick J, Targher G, Smits G, Chonchol M. 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis. 2009;205:255–60.PubMedCrossRefGoogle Scholar
  198. 198.
    Giovannucci E, Liu Y, Hollis BW. RimmEB. 25- hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174–80.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Hsia J, Heiss G, Ren H, et al. Women’s Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115:846–54.PubMedCrossRefGoogle Scholar
  200. 200.
    Avenell A, MacLennan GS, Jenkinson DJ, et al. RECORD Trial Group. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium(RECORD trial). J Clin Endocrinol Metab. 2012;97:614–22.PubMedCrossRefGoogle Scholar
  201. 201.
    Zagami RM, Di Pino A, Urbano F, Piro S, Purrello F, Rabuazzo AM. Low circulating vitamin D levels are associated with increased arterial stiffness in prediabetic subjects identified according to HbA1c. Atherosclerosis. 2015;243(2):395–401.PubMedCrossRefGoogle Scholar
  202. 202.
    Lee JI, Oh SJ, Ha WC, et al. Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes. Diabetes Res Clin Pract. 2012;95:42–7.PubMedCrossRefGoogle Scholar
  203. 203.
    Lieberman R, Wadwa RP, Nguyen N, et al. The association between vitamin D and vascular stiffness in adolescents with and without type 1 diabetes. PloS ONE. 2013;8, e77272.PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    van Schooten FJ, Hirvonen A, Maas LM, et al. Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking and aromatic DNA adduct levels in human right atrial tissue. FASEB J. 1998;12:1409–17.PubMedGoogle Scholar
  205. 205.
    Ortlepp JR, von Korff A, Hanrath P, et al. Vitamin D receptor gene polymorphism Bsml is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of 3441 patients. Eur J Clin Invest. 2003;33:106–9.PubMedCrossRefGoogle Scholar
  206. 206.
    Shanker J, Maitra A, Arvind P, et al. Role of vitamin D levels and vitamin D receptor polymorphisms in relation to coronary artery disease: the Indian atherosclerosis research study. Coron Art Disease. 2011;22:324–32.CrossRefGoogle Scholar
  207. 207.
    Pan XM, Li DR, Yang L, et al. No association between vitamin D receptor polymorphisms and coronary artery disease in a Chinese population. DNA Cell Biol. 2009;28:521–5.PubMedCrossRefGoogle Scholar
  208. 208.
    Maia J, da Silva AS, do Camo RF, et al. The association between vitamin D receptor gene polymorphisms (Taq1 and FokI), type 2 diabetes and micro-macrovascular complications in postmenopausal women. Appl Clin Genet. 2016;9:131–6.PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Engelen L, Schalkwijk CG, Eussen SJ, et al. Low 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 levels are independently associated with macroalbuminuria, but not with retinopathy and macrovascular disease in type 1 diabetes: the EURODIAB prospective complications study. Cardiovasc Diabetol. 2015;14:67.PubMedPubMedCentralCrossRefGoogle Scholar
  210. 210.
    Sugden JA, Davies JI, Witham MD, et al. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med. 2008;25(3):320–5.PubMedCrossRefGoogle Scholar
  211. 211.
    Joergensen C, Reinhard H, Schmedes A, et al. Vitamin D levels and asymptomatic coronary artery disease in type 2 diabetic patients with elevated urinary albumin excretion rate. Diabetes Care. 2012;35(1):168–72.PubMedCrossRefGoogle Scholar
  212. 212.
    Muscogiuri G, Altieri B, Annweiler C, et al. Vitamin D and chronic diseases: the current state of the art. Arch Toxicol. 2016;18 [Epub ahead of print].Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Endocrinology and Metabolism – Diabetes Center, 1st Clinic of Internal MedicineAHEPA University HospitalThessalonikiGreece
  2. 2.Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic MedicineUniversity of Leeds Ringgold Standard InstitutionLeedsUK
  3. 3.Aristotle UniversityThessalonikiGreece

Personalised recommendations