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Current Diabetes Reports

, 19:101 | Cite as

Type 2 Diabetes Mellitus, Insulin Resistance, and Vitamin D

  • Alan SacerdoteEmail author
  • Paulomi Dave
  • Vladimir Lokshin
  • Gül Bahtiyar
Pharmacologic Treatment of Type 2 Diabetes (HE Lebovitz and G Bahtiyar, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pharmacologic Treatment of Type 2 Diabetes

Abstract

Purpose of Review

There is a growing, largely inconsistent, literature on the role of vitamin D in association with type 2 diabetes, insulin resistance/insulin secretion, glycemic indices, and complications of type 2 diabetes. Pathophysiologic, bystander, preventive, and treatment roles of vitamin D have all been proposed. In this focused review, we attempt to organize and clarify our current information in this area.

Recent Findings

Clinical study interpretation is difficult because of variability in dosage, dosage form, study duration, and populations studied, as well as recently reported normal human polymorphisms in vitamin D synthesis and catabolism, vitamin D-binding protein, and vitamin D receptors in addition to a host of potential epigenetic confounders. Low vitamin D status appears to be associated with type 2 diabetes and most other insulin resistance disorders reported to date. The extraskeletal benefits of supplementation/repletion in these disorders in our species, with a few highlighted exceptions, remain to be established.

Summary

This focused review attempts to summarize our current knowledge in this burgeoning area through a review of key meta-analyses, observational studies, randomized control trials, and Mendelian randomization studies and will hopefully serve as a guide to indicate future research directions and current best practice.

Keywords

Vitamin D status T2DM Insulin resistance Diabetes complications Vitamin D deficiency Metabolic syndrome 

Notes

Authors’ Contributions

AS is the corresponding author and reviewed about 65% of the articles cited. PD reviewed about 35% of the articles cited, chiefly those on gout, insulin resistance, and vitamin D, and she also prepared the 1st and 2nd drafts of the summary tables. GB, PD, VL, and AS all reviewed and edited the final presubmission draft.

Compliance with Ethical Standards

Conflict of Interest

Alan Sacerdote, Paulomi Dave, Vladimir Lokshin, and Gül Bahtiyar declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national institutional guidelines).

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Lips P, Eekhoff M, van Schoor N, Oosterwerff M, de Jongh R, Krul-Poel Y, et al. Vitamin D and type 2 diabetes. J Steroid Biochem Mol Biol. 2017;173:280–5. A recent review summarizing reports showing significant positive correlation between serum 1,25-OH-vitamin D (the active form) and both insulin sensitivity and secretion, a negative association between vitamin D deficiency and glycemic control, and a positive association of VDD with incident T2DM.PubMedCrossRefGoogle Scholar
  2. 2.
    •• Gulseth HL, Wium C, Angel K, Eriksen EF, Birkeland KI. Effects of vitamin D supplementation on insulin sensitivity and insulin secretion in subjects with type 2 diabetes and vitamin D deficiency: a randomized controlled trial. Diabetes Care. 2017;40(7):872–8. A recent study of supplementation’s effects on insulin sensitivity and secretion and glycemic indicators in people with T2DM with replete baseline serum 25-OH-vitamin D.PubMedCrossRefGoogle Scholar
  3. 3.
    Nazarian S, St Peter JV, Boston RC, Jones SA, Mariash CN. Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose. Transl Res. 2011 Nov;158(5):276–81.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    • Angellotti E, Pittas AG. The role of vitamin D in the prevention of type 2 diabetes: to D or not to D? Endocrinology. 2017;158(7):2013–21. In this recent focused review despite evidence for prevention from mechanistic and observational studies, a definitive answer regarding T2DM prevention with vitamin D is impossible because reverse causation cannot be excluded.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Pittas AG, Dawson-Hughes B, Sheehan PR, Rosen CJ, Ware JH, Knowler WC, et al. 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
  6. 6.
    Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham N. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Nilas L, Christiansen C. Treatment with vitamin D or its analogues does not change body weight or blood glucose level in postmenopausal women. Int J Obes. 1984;8:407–11.PubMedGoogle Scholar
  8. 8.
    Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. 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
  9. 9.
    •• Santos RKF, Brandão-Lima PN, Tete RMDD, Freire ARS, Pires LV. Vitamin D ratio and glycaemic control in individuals with type 2 diabetes mellitus: a systematic review. Diabetes Metab Res Rev. 2018;34(3). A recent focused review of studies assessing the association of vitamin D status with glycemic indices in people with T2DM. CrossRefGoogle Scholar
  10. 10.
    •• Qu G, Wang L, Tang X, Wu W, Suna Y. The association between vitamin D level and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: an update systematic review and meta-analysis. J Clin Transl Endocrinol. 2017;9:25–31. A recent focused review and meta-analysis of studies exploring associations between vitamin D status and the common diabetic complication of peripheral neuropathy.PubMedPubMedCentralGoogle Scholar
  11. 11.
    •• Hansen CS, Fleischer J, Vistisen D, Ridderstråle M, Jensen JS, Jørgensen ME. High and low vitamin D level is associated with cardiovascular autonomic neuropathy in people with type 1 and type 2 diabetes. Diabet Med. 2017;34(3):364–71. A recent study of the association of vitamin D status with cardiac autonomic neuropathy in people with either T2DM or T1DM.PubMedCrossRefGoogle Scholar
  12. 12.
    Kedar A, Nikitina Y, Henry OR, Abell KB, Vedanarayanan V, Griswold ME, et al. Gastric dysmotility and low serum vitamin D levels in patients with gastroparesis. Horm Metab Res. 2013;45(1):47–53.CrossRefGoogle Scholar
  13. 13.
    •• Basat S, Sivritepe R, Ortaboz D, Sevim Çalık E, Küçük EV, Şimşek B, et al. The relationship between vitamin D level and erectile dysfunction in patients with type 2 diabetes mellitus. Aging Male. 2018;21(2):111–5. An important recent cross-sectional study of the association of erectile dysfunction with vitamin D status.PubMedCrossRefGoogle Scholar
  14. 14.
    •• Luo BA, Gao F, Qin LL. The association between vitamin D deficiency and diabetic retinopathy in type 2 diabetes: a meta-analysis of observational studies. Nutrients. 2017;9(3):307. An important recent study on the association of low vitamin D status and diabetic retinopathy.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    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(10):1189–94.PubMedCrossRefGoogle Scholar
  16. 16.
    Chokhandre MK, Mahmoud MI, Hakami T, Jafer M, Inamdar AS. Vitamin D & its analogues in type 2 diabetic nephropathy: a systematic review. J Diabetes Metab Disord. 2015;14:58.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Li YC. Vitamin D and diabetic nephropathy. Curr Diab Rep. 2008;8(6):464–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Herrmann M, Sullivan DR, Veillard AS, McCorquodale T, Straub IR, Scott R, et al. Serum 25-hydroxyvitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care. 2015;38(3):521–8.PubMedCrossRefGoogle Scholar
  19. 19.
    •• Yu Y, Tian L, Xiao Y, Huang G, Zhang M. Effect of vitamin D supplementation on some inflammatory biomarkers in type 2 diabetes mellitus subjects: a systematic review and meta-analysis of randomized controlled trials. Ann Nutr Metab. 2018;73(1):62–73. A recent focused review and meta-analysis of interventional RCTs studying impact of vitamin D supplementation on surrogate markers for macrovascular complications.PubMedCrossRefGoogle Scholar
  20. 20.
    Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014;114:379–93.PubMedCrossRefGoogle Scholar
  21. 21.
    •• Li DM, Zhang Y, Li Q, Xu XH, Ding B, Ma JH. Low 25-hydroxyvitamin D level is associated with peripheral arterial disease in type 2 diabetes patients. Arch Med Res. 2016;47(1):49–54. A recent cross-sectional study exploring the association of low vitamin D status with peripheral arterial disease.PubMedCrossRefGoogle Scholar
  22. 22.
    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(10):2238–43.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    •• Barchetta I, Cimini FA, Cavallo MG. Vitamin D supplementation and non-alcoholic fatty liver disease: present and future. Nutrients. 2017;9(9):1015. Recent focused review of observational studies on associations between low vitamin D status and NAFLD and intervention studies.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Kim JJ, Choi YM, Chae SJ, Hwang KR, Yoon SH, Kim MJ, et al. Vitamin D deficiency in women with polycystic ovary syndrome. Clin Exp Reprod Med. 2014;41(2):80–5.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Panidis D, Balaris C, Farmakiotis D, Rousso D, Kourtis A, Balaris V, et al. Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome. Clin Chem. 2005;51:1691–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, et al. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2006;114:577–83.CrossRefGoogle Scholar
  27. 27.
    Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, et al. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol. 2009;161:575–82.PubMedCrossRefGoogle Scholar
  28. 28.
    Mahmoudi T, Gourabi H, Ashrafi M, Yazdi RS, Ezabadi Z. Calciotropic hormones, insulin resistance, and the polycystic ovary syndrome. Fertil Steril. 2010;93:1208–14.PubMedCrossRefGoogle Scholar
  29. 29.
    Selimoglu H, Duran C, Kiyici S, Ersoy C, Guclu M, Ozkaya G, et al. The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome. J Endocrinol Investig. 2010;33:234–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Li HW, Brereton RE, Anderson RA, Wallace AM, Ho CK. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism. 2011;60:1475–81.PubMedCrossRefGoogle Scholar
  31. 31.
    Ngo DT, Chan WP, Rajendran S, Heresztyn T, Amarasekera A, Sverdlov AL, et al. Determinants of insulin responsiveness in young women: impact of polycystic ovarian syndrome, nitric oxide, and vitamin D. Nitric Oxide. 2011;25:326–30.PubMedCrossRefGoogle Scholar
  32. 32.
    Ranjzad F, Mahban A, Shemirani AI, Mahmoudi T, Vahedi M, Nikzamir A, et al. Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet. 2011;28:225–32.PubMedCrossRefGoogle Scholar
  33. 33.
    Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol. 2011;164:741–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Mazloomi S, Sharifi F, Hajihosseini R, Kalantari S, Mazloomzadeh S. Association between hypoadiponectinemia and low serum concentrations of calcium and vitamin D in women with polycystic ovary syndrome. ISRN Endocrinol. 2012;2012:949427.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Muscogiuri G, Policola C, Prioletta A, Sorice G, Mezza T, Lassandro A, et al. Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS? Clin Nutr. 2012;31:476–80.PubMedCrossRefGoogle Scholar
  36. 36.
    El-Shal AS, Shalaby SM, Aly NM, Rashad NM, Abdelaziz AM. Genetic variation in the vitamin D receptor gene and vitamin D serum levels in Egyptian women with polycystic ovary syndrome. Mol Biol Rep. 2013;40:6063–73.PubMedCrossRefGoogle Scholar
  37. 37.
    Krul-Poel YH, Snackey C, Louwers Y, Lips P, Lambalk CB, Laven JS, et al. The role of vitamin D in metabolic disturbances in polycystic ovary syndrome: a systematic review. Eur J Endocrinol. 2013;169:853–65.PubMedCrossRefGoogle Scholar
  38. 38.
    Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol. 2012;77:343–50.CrossRefGoogle Scholar
  39. 39.
    Yildizhan R, Kurdoglu M, Adali E, Kolusari A, Yildizhan B, Sahin HG, et al. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet. 2009;280:559–63.PubMedCrossRefGoogle Scholar
  40. 40.
    Thys-Jacobs S, Donovan D, Papadopoulos A, Sarrel P, Bilezikian JP. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids. 1999;64:430–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Kotsa K, Yavropoulou MP, Anastasiou O, Yovos JG. Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome. Fertil Steril. 2009;92:1053–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Wehr E, Pieber TR, Obermayer-Pietsch B. Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Investig. 2011;34:757–63.Google Scholar
  43. 43.
    Prentice A. Vitamin D deficiency: a global perspective. Nutr Rev. 2008;66:S153–64.PubMedCrossRefGoogle Scholar
  44. 44.
    Lips P. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. 2010;121:297–300.PubMedCrossRefGoogle Scholar
  45. 45.
    Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010;95:471–8.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Butts SF, Seifer DB, Koelper N, et al. Vitamin D deficiency is associated with poor ovarian stimulation outcome in PCOS but not unexplained infertility. J Clin Endocrinol Metab. 2019;104(2):369–78.PubMedCrossRefGoogle Scholar
  47. 47.
    Kuliczkowska-Plaksej J, Pasquali R, Milewicz A, et al. Serum vitamin D binding protein level associated with metabolic cardiovascular risk factors in women with the polycystic ovary syndrome. Horm Metab Res. 2019;51(1):54–61.PubMedCrossRefGoogle Scholar
  48. 48.
    Fang F, Ni K, Cai Y, Shang J, Zhang X, Xiong C. Effect of vitamin D supplementation on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Complement Ther Clin Pract. 2017;26:53–60.PubMedCrossRefGoogle Scholar
  49. 49.
    Mogili KD, Karuppusami R, Thomas S, Chandy A, Kamath MS, TKA. Prevalence of vitamin D deficiency in infertile women with polycystic ovarian syndrome and its association with metabolic syndrome - a prospective observational study. Eur J Obstet Gynecol Reprod Biol. 2018;229:15–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Rashidi B, Haghollahi F, Shariat M, Zayerii F. The effects of calcium-vitamin D and metformin on polycystic ovary syndrome: a pilot study. Taiwan J Obstet Gynecol. 2009;48(2):142–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Speiser PW, Serrat J, New MI, Gertner JM. Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1992;75:1421–4.PubMedGoogle Scholar
  52. 52.
    Saygili F, Oge A, Yilmaz C. Hyperinsulinemia and insulin insensitivity in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: the relationship between serum leptin levels and chronic hyperinsulinemia. Horm Res. 2005;63(6):270–4.PubMedGoogle Scholar
  53. 53.
    Charmandari E, Weise M, Bornstein SR, Eisenhofer G, Keil MF, Chrousos GP, et al. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications. J Clin Endocrinol Metab. 2002;87(5):2114–20.CrossRefGoogle Scholar
  54. 54.
    Sacerdote A, Bahtiyar G “Treatment of congenital adrenal hyperplasia by reducing insulin resistance and cysticercosis induced polycystic ovarian syndrome,” in Darwish A editor Contemporary Gynecologic Practice, A. Darwish, Ed., InTech; 2015.Google Scholar
  55. 55.
    Bahtiyar G, Sacerdote A. “Management approaches to congenital adrenal hyperplasia in adolescents and adults; latest therapeutic developments,” in Chatterjee A editor Amenorrhea, InTech; 2011.Google Scholar
  56. 56.
    Thomas N, Kalani A, Vincent R, Luis Lam M, Bahtiyar G, Borensztein A, et al. Effect of vitamin D in a patient with classical adrenal hyperplasia due to 11-hydroxylase deficiency. J Med Cases. 2013;4(8):569–75.Google Scholar
  57. 57.
    Luis Lam M, Sacerdote AS, Bahtiyar G. Normalization of serum 11-deoxycortisol in a patient with non-classic adrenal hyperplasia due to 11-hydroxylase deficiency treated with vitamin D and a glucagon-like peptide(GLP)-1 agonist. Presented at The 96th Annual Meeting of The Endocrine Society, 6/21/2014, Chicago, IL. Presentation Number: SAT-0763.Google Scholar
  58. 58.
    Gröber U, Kisters K. Influence of drugs on vitamin D and calcium metabolism. Dermatoendocrinol. 2012;4(2):158–66.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Dono E, Inoue T, Ezeji G, Baby A, Bahtiyar G, Sacerdote AS. Amelioration of non-classic 11-hydroxylase deficiency in a vitamin D deficient patient with weight loss and ergocalciferol. press.endocrine.org/doi/abs/10.1210/endo-meetings.2015.AHPAA.7.THR-415.Google Scholar
  60. 60.
    Sacerdote, A.: Weight-dependent expression of non-classical aldosterone synthase deficiency. Program and Abstracts, Endo-2002, The Endocrine Society’s 84th Annual Meeting: 599, 2002.Google Scholar
  61. 61.
    Lundqvist J, Wikvall K, Norlin M. Vitamin D-mediated regulation of CYP21A2 transcription – a novel mechanism for vitamin D action. BiochimBiophysActa. 1820;2012:1553–9.Google Scholar
  62. 62.
    Fenteany G, Inoue T, Bahtiyar G, Sacerdote AS. Association of vitamin D repletion with normalization of elevated serum 17- OH-progesterone. Med Cas Rep. 2017;3:3.Google Scholar
  63. 63.
    Krysiak R, Kowalcze K, Bednarska-Czerwińska A, Okopień B. The effect of simvastatin treatment on plasma steroid levels in females with non-classic congenital adrenal hyperplasia. Exp Clin Endocrinol Diabetes. 2016;124(04):215–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Smith E, Hoy D, Cross M, Merriman TR, Vos T, Buchbinder R, et al. The global burden of gout: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73:1470–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Roddy E, Doherty M. Gout. Epidemiology of gout. Arthritis Res Ther. 2010;12:223.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol. 2015;11:649–62.PubMedCrossRefGoogle Scholar
  67. 67.
    Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet. 2016;388:2039–52.PubMedCrossRefGoogle Scholar
  68. 68.
    Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Curr Opin Cardiol. 2006;21(1):1–6.PubMedCrossRefGoogle Scholar
  69. 69.
    International Diabetes Federation (IDF): The IDF consensus worldwide definition of the metabolic syndrome. https://www.idf.org/e-library/consensus-statements/60-idfconsensus-worldwide-definitionof-the-metabolic
  70. 70.
    Yu TY, Jee JH, Bae JC, Jin SM, Baek JH, Lee MK, et al. Serum uric acid: a strong and independent predictor of metabolic syndrome after adjusting for body composition. Metab Clin Exp. 2016;65:432–40.PubMedCrossRefGoogle Scholar
  71. 71.
    Yuan H, Yu C, Li X, Sun L, Zhu X, Zhao C, et al. Serum uric acid levels and risk of metabolic syndrome: a dose-response meta-analysis of prospective studies. J Clin Endocrinol Metab. 2015;100:4198–207.PubMedCrossRefGoogle Scholar
  72. 72.
    De Oliveira EP, Burini RC. High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr. 2012;4:2.CrossRefGoogle Scholar
  73. 73.
    Perez-Ruiz F, Aniel-Quiroga MA, Herrero-Beites AM, Chinchilla SP, Erauskin GG, Merriman T. Renal clearance of uric acid is linked to insulin resistance and lower excretion of sodium in gout patients. Rheumatol Int. 2015;35:1519–24.PubMedCrossRefGoogle Scholar
  74. 74.
    Jung JH, Song GG, Ji JD, Lee YH, Kim JH, Seo YH, et al. Metabolic syndrome: prevalence and risk factors in Korean gout patients. Korean J Intern Med. 2018;33(4):815–22.PubMedCrossRefGoogle Scholar
  75. 75.
    Adachi S, Yoshizawa F, Yagasaki K. Hyperuricemia in type 2 diabetic model KK-Ay/Ta mice: a potent animal model with positive correlation between insulin resistance and plasma high uric acid levels. BMC Res Notes. 2017;10(1):577.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Pereira RM, De Carvalho JF, Bonfa E. Metabolic syndrome in rheumatological diseases. Autoimmun Rev. 2009;8:415–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Fraile JM, Puig JG, Torres RJ, de Miguel E, Martínez P, Vázquez JJ. Uric acid metabolism in patients with primary gout and the metabolic syndrome. Nucleosides Nucleotides Nucleic Acids. 2010;29:330–4.PubMedCrossRefGoogle Scholar
  78. 78.
    Niu SW, Chang KT, Lin HY, Kuo IC, Chang YH, Chen YH, et al. Decreased incidence of gout in diabetic patients using pioglitazone. Rheumatology (Oxford). 2018;57(1):92–9.CrossRefGoogle Scholar
  79. 79.
    Chen W, Roncal-Jimenez C, Lanaspa M, Gerard S, Chonchol M, Johnson RJ, et al. Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo. Metabolism. 2014;63:150–60.PubMedCrossRefGoogle Scholar
  80. 80.
    Vanholder R, Patel S, Hsu CH. Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure. J Am Soc Nephrol. 1993;4:1035–8.PubMedGoogle Scholar
  81. 81.
    Takahashi S, Yamamoto T, Moriwaki Y, Tsutsumi Z, Yamakita JI, Higashino K. Decreased serum concentrations of 1,25(OH)2 vitamin D3 in patients with gout. Metabolism. 1998;47:336–8.PubMedCrossRefGoogle Scholar
  82. 82.
    •• Sipahi S, Acikgoz SB, Genc AB, Yildirim M, Solak Y, Tamer A. The association of vitamin D status and vitamin D replacement therapy with glycemic control, serum uric acid levels, and microalbuminuria in patients with type 2 diabetes and chronic kidney disease. Med Princ Pract. 2017;26:146–51. A recent study of associations between vitamin D status and glycemic indicators and renal function in people with T2DM and CKD.PubMedCrossRefGoogle Scholar
  83. 83.
    Hayashino Y, Okamura S, Tsujii S, Ishii H. Association of serum uric acid levels with the risk of development or progression of albuminuria among Japanese patients with type 2 diabetes: a prospective cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT 10]). Acta Diabetol. 2016;53:599–607.PubMedCrossRefGoogle Scholar
  84. 84.
    Peng H, Li H, Li C, Chao X, Zhang Q, Zhang Y. Association between vitamin D insufficiency and elevated serum uric acid among middle-aged and elderly Chinese Han women. PLoS One. 2013;8(4):e61159.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Yandı YE, Gencer E, Kılavuz B, Baki AE, Şahin H, Bilici M, et al. Cyanocobalamin and 25-hydroxy vitamin D levels in gout patients: an overlooked issue. Open Journal of Rheumatology and Autoimmune Diseases. 2016;6:96–101.CrossRefGoogle Scholar
  86. 86.
    •• Langer-Gould A, Lucas RM, Xiang AH, Wu J, Chen LH, Gonzales E, Haraszti S, Smith JB, Quach H, Barcellos LF. Vitamin D-binding protein polymorphisms, 25-hydroxyvitamin D, sunshine and multiple sclerosis. Nutrients. 2018;10(2). An important recent discussion about how VDBP polymorphisms affect the biologic expression of vitamin D. Google Scholar
  87. 87.
    Mathieu C. Vitamin D and diabetes: where do we stand? Diabetes Res Clin Pract. 2015;108:201–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Al-Shoumer KA, Al-Essa TM. Is there a relationship between vitamin D with insulin resistance and diabetes mellitus? World J Diabetes. 2015;6:1057–64.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Pittas AG, Nelson J, Mitri J, Hillmann W, Garganta C, Nathan DM, et al. Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program. Diabetes Care. 2012;35:565–373.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Thomas GN, ó Hartaigh B, Bosch JA, et al. Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Diabetes Care. 2012;35:1158–64.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Sinotte M, Diorio C, Bérubé S, Pollak M, Brisson J. Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr. 2009;89(2):634–40.PubMedCrossRefGoogle Scholar
  92. 92.
    Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006;371(1–2):1–12.PubMedCrossRefGoogle Scholar
  93. 93.
    •• Al-Daghri NM, Mohammed AK, Al-Attas OS, Ansari MGA, Wani K, Hussain SD, Sabico S, Tripathi G, Majed S, Alokail MS. Vitamin D receptor gene polymorphisms modify cardiometabolic response to vitamin D supplementation in T2DM patients. Sci Rep 2017, Article number: 8280. An important 1 year vitamin D intervention trial assessing cardiometabolic effects of vitamin D administration as a function of vitamin D receptor polymorphisms. Google Scholar
  94. 94.
    Jacobs ET, Van Pelt C, Forster RE, Zaidi W, Hibler EA, Galligan MA, et al. CYP24A1 and CYP27B1 polymorphisms modulate vitamin D metabolism in colon cancer cells. Cancer Res. 2013;73(8):2563–73.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    •• Bahrami A, Sadeghnia HR, Tabatabaeizadeh SA, Bahrami-Taghanaki H, Behboodi N, Esmaeili H, et al. Genetic and epigenetic factors influencing vitamin D status. J Cell Physiol. 2018;233(5):4033–43. A good recent review of genetic and epigenetic influences on vitamin D status.PubMedCrossRefGoogle Scholar
  96. 96.
    Ye Z, Sharpe SJ, Burgess S, Scott RA, Imamura F, Langenberg C, et al. Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2015;3(1):P35–42.CrossRefGoogle Scholar
  97. 97.
    Lu L, Bennett DA, Millwood IY, Parish S, McCarthy MI, Mahajan A, et al. Mendelian randomization study in European and Chinese adults. PLoS Med. 2018;15(5):e1002566. A recent Mendelian randomization study in which only 2 SNPs associated with vitamin D synthesis, for which possible pleiotropic effects on incident T2DM risk had been excluded, from which the investigators were able to infer a causative, genetically instrumented protective effect of vitamin D against incident T2DM.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    •• Pittas AG, Dawson-Hughes B, Patricia Sheehan P et al. for the D2d Research Group. Vitamin D supplementation and prevention of type 2 diabetes. June 7, 2019.  https://doi.org/10.1056/NEJMoa1900906. The largest randomized, placebo-controlled vitamin D intervention study to date in people at high risk for incident T2DM not preselected for vitamin D deficiency. PubMedCrossRefGoogle Scholar
  99. 99.
    Matyjaszek-Matuszek B, Lenart-Lipińska M, Woźniakowska E. Clinical implications of vitamin D deficiency. Prz Menopauzalny. 2015;14:75–81.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Kajbaf F, Mentaverri R, Diouf M, Fournier A, Kamel S, Lalau JD. The association between 25-hydroxyvitamin D and hemoglobin A1c levels in patients with type 2 diabetes and stage 1-5 chronic kidney disease. Int J Endocrinol. 2014;2014:142468–6.  https://doi.org/10.1155/2014/142468.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86:50–60.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–8.PubMedCrossRefGoogle Scholar
  103. 103.
    Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71:31–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Alan Sacerdote
    • 1
    • 2
    • 3
    • 4
    Email author
  • Paulomi Dave
    • 5
  • Vladimir Lokshin
    • 2
  • Gül Bahtiyar
    • 1
    • 2
    • 3
    • 4
  1. 1.Division with EndocrinologyNew York City Health + Hospitals/WoodhullBrooklynUSA
  2. 2.Division of EndocrinologySUNY Downstate Medical CenterBrooklynUSA
  3. 3.NYU School of MedicineNew YorkUSA
  4. 4.St. George’s UniversitySt. George’sGrenada
  5. 5.Department of MedicineNew York City Health + Hospitals/WoodhullBrooklynUSA

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