Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 144 No. 1112 (2014)

Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study

  • Sigrid Jehle
  • Alessia Lardi
  • Barbara Felix
  • Henry N. Hulter
  • Christoph Stettler
  • Reto Krapf
Cite this as:
Swiss Med Wkly. 2014;144:w13942


OBJECTIVE: Vitamin D (D3) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA1c) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM.

MATERIALS AND METHODS: We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D3 or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA1c levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values.

RESULTS: After 6 months of D3 supply, there was a significant intergroup difference in the change in HbA1c levels (relative change [mean ± standard deviation] +2.9% ± 1.5% in the D3group vs +6.9% ± 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% ± 5.6% in the D3group and increased by 10% ± 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D3 group from 200 ± 41 to 126 ± 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints.

CONCLUSIONS: D3 improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA1c positively compared with placebo in patients with T2DM.

Clinical trial registration number at NCT01585051


  1. Baz-Hecht M, Goldfine AB. The impact of vitamin D deficiency on diabetes and cardiovascular risk. Curr Opin Endocrinol Diabetes Obes. 2010;17:113–9.
  2. 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.
  3. 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.
  4. Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 2 1980;09(4458):823–5.
  5. Alvarez JA, Ashraf A. 2010 Role of vitamin D in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol. 2010;351–85.
  6. Tai K, Need AG, Horowitz M, Chapman IM. Vitamin D, glucose, and insulin sensitivity. Nutrition. 2008;24:279–85.
  7. Boer IH, Tinker LF, Connelly S, Curb JD, 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.
  8. Grimnes G, Figenschau Y, Almas B, Jorde R. Vitamin D, insulin secretion, sensitivity and lipids, Diabetes. 2011;60:2748–57.
  9. 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(4):980–6.
  10. Tai K, Need AG, Horowitz, Chapman IM. Glucose tolerance and vitamin D: Effects of treating vitamin D deficiency. Nutrition. 2008;24:950–6.
  11. Mitri J, Dawson-Hughes B, Hu FB, Pittas A. Effects of vitamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes. Am J Clin Nutr. 2011;94:486–94.
  12. 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.
  13. Eftekhari MH, Akbarzadeh M, Dabbaghmanesh MH, Hasanzadeh J. Impact of treatment with oral calcitriol on glucose indices in type 2 diabetes mellitus patients. Asia Pac J Clin Nutr. 2011;20(4):521–6.
  14. Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian MR, Houshiarrad A, Gharavi A, et al. Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial. BMC Med. 2011;9:125–31.
  15. Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian MR, Houshiarrad A, Kalayi A, et al. Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes Metab Res Rev. 2012;28(5):424–30.
  16. Neyestani TR, Nikooyeh B, Alavi-Majd H, Shariatzadeh N, Kalayi A, Tayebinejad N, et al. Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes. J Clin Endocrinol Metab. 9 2012;7(6):2005–11.
  17. Nikooyeh B, Neyestani TR, Farvid M, Alavi-Majd H, Houshiarrad A, Kalayi A, et al. Daily consumption of vitamin D- or vitamin D + calcium-fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial. Am J Clin Nutr. 2011;93(4):764–71.
  18. Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract. 2003;57(4):258–61.
  19. Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25–hydroxyvitamin D levels. Eur J Nutr. 2009;48(6):349–54.
  20. 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(4):600–8.
  21. 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.
  22. Krapf R, Beeler I, Hertner D, Hulter NH. Chronic respiratory alkalosis. N Engl J Med. 1991;324:1394–401.
  23. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.
  24. Holick MF. Vitamin D deficiency. N Engl J Med. 2007:357:266–81.
  25. Wallace TM, Levy JC, Matthwes DR. Use and Abuse of HOMA modeling. Diabetes Care. 2004;27:1487–95.
  26. Adorini L. Regulation of immune responses by vitamin D receptor ligands, in “Vitamin D”, 2nd edition, Elsevier, 2008, Feldman D, Pike JW, Glorieux FH, eds, pp 631–48.
  27. Li YC, Kong J, Wie M, Chen ZF, Liu SQ, Cao LP. 1,25 dihydroxy vitamin D is a negative regulator of the renin-angiotensin system. J Clin Invest. 2002;110:229–38.
  28. Li YC. Vitamin D and the Renin-Angiotensin System, in “Vitamin D” 2nd edition, Elsevier, 2005, Feldman D, Pike YW, Glorieux FH, eds, pp 871–72.
  29. Fiscella KA, Winters PC, Ogedegbe G. Vitamin D and racial disparity in albuminuria: NHANES 2001–2006. Am J Hypertens. 2011;24:1114–20.
  30. de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, 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.
  31. Tang WJ, Wang LF, Xu XY, Zhou Y, Jin WF, Wang HF, Gao J. Autocrine/paracrine action of vitamin D on FGF-23 expression in cultured rat osteoblasts Calcified Tissue Int. 2010;86:404–10.
  32. Faul C, Maaral AP, Oskouei B, H MC et al. FGF-23 induces left ventricular hypertrophy. J Clin Invest. 2011;121:4393–408.
  33. Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359(6):584–92.
  34. Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M, et al. The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med. 2010;152(10):640–8.
  35. Taylor EN, Rimm EB, Stampfer MJ, Curhan GC. Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease. Am Heart J. 2011;161:956–62.
  36. Arnlov J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L, Larsson TE. Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community. Kidney Int. 2013;83:160–6.
  37. Yoda K, Imanishi Y, Yoda M, Mishima T, Ichii M, Yamada S, et al. Impaired response of FGF-23 to oral phosphate in patients with type 2 diabetes: a possible mechanism of atherosclerosis J Clin Endocrinol Metab. 2012;97(11):E2036–43.
  38. Reaven PD, Sacks J, Investigators for the VADT. Coronary artery and abdominal aortic calcification are associated with cardiovascular disease in type 2 diabetes. Diabetologica. 2005;48:379–85.
  39. Villarino ME, Sánchez LM, Bozal CB, Ubios AM. Influence of short-term diabetes on osteocytic lacunae of alveolar bone. A histomorphometric study. Acta Odontol Latinoam. 2006;19(1):23–8.
  40. Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142(2):309–19.
  41. Burnett-Bowie SA, Leder BZ, Henao MP, Baldwin CM, Hayden DL, Finkelstein JS. Randomized trial assessing the effects of ergocalciferol administration on circulating FGF-23. Clin J Am Soc Nephrol. 2012;7:624–31.