The total and free vitamin D in type 2 diabetes mellitus patients in Baghdad city

Free and total vitamin D

Authors

  • Zainab J. Subber Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq
  • Ghassan A. Al-Shamma Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq
  • Hashim M. Hashim Department of Medicine, College of Medicine, Al-Nahrain University, Baghdad, Iraq

DOI:

https://doi.org/10.47419/bjbabs.v2i02.41

Keywords:

Bikle method, Bioavailable vitamin D, Free vitamin D, Total vitamin D, Type 2 diabetes mellitus, Vermeulen method

Abstract

Background: The free-form of vitamin D has been used by many researchers as an index of vitamin D status in health and disease. Several methods are there to estimate free, total, and even bioavailable vitamin D.

Objective: The present work was carried out to measure free vitamin D using a special formula suggested by Bikle and Schwartz in 2019, which includes the vitamin D binding protein (VDBP). The results will be used to evaluate the vitamin D status in patients with type 2 diabetes mellitus (T2DM), and its relation to the disease progression.

Methods: Sixty-four patients with T2DM and 73 healthy subjects, all from Baghdad city, were enrolled in the current study from March to October 2020. For each participant, fasting blood glucose, hemoglobin (HbA1c), insulin resistance HOMA-IR, and body mass index (BMI) were measured in addition to the total vitamin D and VDBP. Moreover, free vitamin D was calculated by the formula of Bikle & Schwartz.

Results: There were highly significant correlations between total vitamin D and absolute values of free vitamin D or its percentage. The difference in total vitamin D was significant between patients and healthy controls with no significant change in VDBP, free and bio-available vitamin D, while free vitamin D% was higher in the patient’s group. Correlations between vitamin D and each of BMI, fasting glucose, HbA1c, and HOMA-IR were not significant; however, there was a negative correlation with BMI and fasting glucose in the healthy control subjects only. The Receiver Operating Characteristic (ROC) curve analysis of vitamin D in the diagnosis of diabetes mellitus was poor.

Conclusion: Total vitamin D can represent vitamin D status, but it cannot be used as a factor for diagnosing T2DM. However, it could be of importance to change the glycemic status.

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References

John F Aloia. “African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox”. Am J Clin Nutr 88(2) (2008), 545S–550S. DOI: 10.1093/ajcn/88.2.545S.

N S Alzaman et al. “Vitamin D status of black and white Americans and changes in vitamin D metabolites after varied doses of vitamin D supplementation”. Am J Clin Nutr 104(1) (2016), pp. 205–214. DOI: 10.3945/ajcn.115.129478.

I Kostoglou- Athanassiou et al. “Vitamin D and glycemic control in diabetes mellitus type 2”. Ther Adv Endocrinol Metab 4(4) (2013), pp. 122–128. DOI: 10.1177/2042018813501189.

A Bener et al. “High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children”. Acta Diabetol 46(3) (2009), pp. 183–189. DOI: 10.1007/s00592-008-0071-6.

I Bhan et al. “ Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients”. Kidney Int 82(1) (2012), pp. 84–89. DOI: 10.1038/ki.2012.19.

D D Bikle and J Schwartz. “Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions”. Front Endocrinol 10 (2019), p. 317. DOI: 10.3389/fendo.2019.00317.

D D Bikle et al. “Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein”. J Clin Endocrinol Metab 63(4) (1986), pp. 954–959. DOI: 10.1210/jcem-63-4-954.

Daniel Bikle. “Nonclassic actions of vitamin D”. J Clin Endocrinol Metab 94(1) (2009), pp. 26–34. DOI: 10.1210/jc.2008-1454.

B Bouillon. “The vitamin D binding protein”. In: Vitamin D. Ed. by D Feldman, J W Pike, J Adams, et al. Vol. 31. London: Elsevier, 2016, pp. 57–72.

Roger Bouillon. “Free or Total 25OHD as Marker for Vitamin D Status?” J Bone Miner Res 31(6) (2016), pp. 1124–1127. DOI: 10.1002/jbmr.2871.

Maria Callejo et al. “Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension”. J Clin Med 9(2) (2020), p. 448. DOI: 10.3390/jcm9020448.

J A Cauley et al. “Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women’s Health Initiative (WHI)”. J Bone Miner Res 26(10) (2011), pp. 2378–2388. DOI: 10.1002/jbmr.449.

Rene F Chun et al. “ Vitamin D and DBP: the free hormone hypothesis revisited”. J Steroid Biochem 144 Pt A (2014), pp. 132–137. DOI: 10.1016/j.jsbmb.2013.09.012.

Z Dastani et al. “In healthy adults, biological activity of vitamin D, as assessed by serum PTH, is largely independent of DBP concentrations”. J Bone Miner Res 29(2) (2014), pp. 494–499. DOI: 10.1002/jbmr.2042.

Z Dastani et al. “In healthy adults, biological activity of vitamin D, as assessed by serum PTH, is largely independent of DBP concentrations”. J Bone Miner Res 29(2) (2014), pp. 494–499. DOI: 10.1002/jbmr.2042.

C Esteban et al. “Receptor-mediated uptake and processing of vitamin D-binding protein in human B-lymphoid cells”. J Biol Chem 267(14) (1992), pp. 10177–10183. DOI: 10.1016/S0021-9258(19)50216-2.

M G Fakih et al. “A phase I pharmacokinetic and pharmacodynamic study of intravenous calcitriol in combination with oral gefitinib in patients with advanced solid tumors”. Clin Cancer Res 13(4) (2007). DOI: 10.1158/1078-0432.CCR-06-1165.

D Giri et al. “Treating vitamin D deficiency in children with type I diabetes could improve their glycaemic control”. BMC Res Notes 10(1) (2017), p. 465. DOI: 10.1186/s13104-017-2794-3.

M Hewison. “Vitamin D and the intracrinology of innate immunity”. Mol Cell Endocrinol. 321(2) (2010), pp. 103–111. DOI: 10.1016/j.mce.2010.02.013.

Martin Hewison et al. “Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease”. J Steroid Biochem Mol Biol 103(3-5) (2007), pp. 316–321. DOI: 10.1016/j.jsbmb.2006.12.078.

Michael F Holick. “Bioavailability of vitamin D and its metabolites in black and white adults”. N Engl J Med 369(21) (2013), pp. 2047–2048. DOI: 10.1056/NEJMe1312291.

Michael F. Holick. “Vitamin D Deficiency”. New England Journal of Medicine 357(3) (2007), pp. 266–281. DOI: 10.1056/nejmra070553.

Z Hu et al. “Efficacy of vitamin D supplementation on glycemic control in type 2 diabetes patients”. Medicine 98(14) (2019), e14970. DOI: 10.1097/MD.0000000000014970.

M S Johnsen et al. “Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D”. Scand J Clin Lab Invest 74(3) (2014), pp. 177–183. DOI: 10.3109/00365513.2013.869701.

H J Kalkwarf et al. “The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race”. J Clin Endocrinol Metab 92(6) (2007), pp. 2087–2099. DOI: 10.1210/jc.2006-2553.

S Kayaniyil et al. “Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes”. Diabetes Care 33(6) (2010), pp. 1379–1381. DOI: 10.2337/dc09-2321.

X Li et al. “The Effect of Vitamin D Supplementation on Glycemic Control in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis”. Nutrients 10(3) (2018), p. 375. DOI: 10.3390/nu10030375.

S - Lundgren et al. “Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein”. J Histochem Cytochem 45(3) (1997), pp. 383–392. DOI: 10.1177/002215549704500306.

P L Lutsey et al. “The 25-hydroxyvitamin D3 C-3 epimer: distribution, correlates, and reclassification of 25-hydroxyvitamin D status in the population-based Atherosclerosis Risk in Communities Study (ARIC)”. Clin Chim Acta 442 (2015), pp. 75–81. DOI: 10.1016/j.cca.2014.12.036.

N Mirhosseini et al. “Vitamin D Supplementation, Glycemic Control, and Insulin Resistance in Prediabetics: A Meta-Analysis”. J Endocr Soc 2(7) (2018), pp. 687–709. DOI: 10.1210/js.2017-00472.

J Mitri et al. “Effects of vitamin D and calcium supplementation on pancreatic β 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 94(2) (2011), pp. 486–494. DOI: 10.3945/ajcn.111.011684.

C M Nielson et al. “Role of Assay Type in Determining Free 25-Hydroxyvitamin D Levels in Diverse Populations”. N Engl J Med 374(17) (2016), pp. 1695–1696. DOI: 10.1056/NEJMc1513502.

T O Jemielita et al. “Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays”. Osteoporos Int 27(2) (2016), pp. 617–626. DOI: 10.1007/s00198-015-3296-6.

Ziad H Al-oanzi et al. “ Assessment of vitamin D status in male osteoporosis”. Clin Chem. 52(2) (2006), pp. 248–254. DOI: 10.1373/clinchem.2005.059568.

S - Olt. “Relationship between vitamin D and glycemic control in patients with type 2 diabetes mellitus”. Int J Clin Exp Med 8(10) (2015), pp. 19180–19183.

I Papaioannou et al. “Vitamin D Deficiency in Elderly With Diabetes Mellitus Type 2: A Review”. Cureus 13(1) (2021), e12506. DOI: 10.7759/cureus.12506.

S Penckofer et al. “Vitamin D and diabetes: let the sunshine in”. Diabetes Educ 34(6) (2008), pp. 939–940. DOI: 10.1177/0145721708326764.

A G Pittas et al. “Vitamin D Supplementation and Prevention of Type 2 Diabetes”. N Engl J Med 381(6) (2019), pp. 520–530. DOI: 10.1056/NEJMoa1900906.

C E Powe et al. “Vitamin D–Binding Protein Modifies the Vitamin D–Bone Mineral Density Relationship”. J Bone Miner Res 26(7) (2011), pp. 1609–1616. DOI: 10.1002/jbmr.387.

“Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium”. In: Dietary Reference Intakes for Calcium and Vitamin D. Ed. by A C Ross et al. Washington (DC): National Academies Press (US), 2011. DOI: 10.17226/13050.

M C Sachs et al. “Estimating mean annual 25-hydroxyvitamin D concentrations from single measurements: the Multi-Ethnic Study of Atherosclerosis”. Am J Clin Nutr 97(6) (2013), pp. 1243–1251. DOI: 10.3945/ajcn.112.054502.

J B Schwartz, L Kane, and D Bikle. “Response of Vitamin D Concentration to Vitamin D3 Administration in Older Adults without Sun Exposure: A Randomized Double-Blind Trial”. J Am Geriatr Soc 64(1) (2016), pp. 65–72. DOI: 10.1111/jgs.13774.

J B Schwartz et al. “A Comparison of Measured and Calculated Free 25(OH) Vitamin D Levels in Clinical Populations”. J Clin Endocrinol Metab 99(5) (2014), pp. 1631–1637. DOI: 10.1210/jc.2013-3874.

J C Seida et al. “Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis”. The Journal of Clinical Endocrinology & Metabolism 99(10) (2014), pp. 3551–3560. DOI: 10.1210/jc.2014-2136.

C T Sempos et al. “Developing vitamin D dietary guidelines and the lack of 25-hydroxyvitamin D assay standardization: The ever-present past”. J Steroid Biochem Mol Biol 164 (2016), pp. 115–119. DOI: 10.1016/j.jsbmb.2015.08.027.

C T Sempos et al. “Vitamin D status as an international issue: national surveys and the problem of standardization”. Scand J Clin Lab Invest Suppl 243 (2012), pp. 32–40. DOI: 10.3109/00365513.2012.681935.

S T Sollid et al. “Effects of vitamin D binding protein phenotypes and vitamin D supplementation on serum total 25(OH)D and directly measured free 25(OH)D”. Eur J Endocrinol 174(4) (2016). DOI: 10.1530/EJE-15-1089.

D Somjen et al. “25-hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds”. Circulation 111(13) (2005), pp. 1666–1671. DOI: 10.1161/01.CIR.0000160353.27927.70.

Y Song et al. “Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies”. Diabetes Care 36(5) (2013), pp. 1422–1428. DOI: 10.2337/dc12-0962.

H Tang et al. “Effects of Vitamin D Supplementation on Glucose and Insulin Homeostasis and Incident Diabetes among Nondiabetic Adults: A Meta-Analysis of Randomized Controlled Trials”. International Journal of Endocrinology 2018(Article ID 7908764) (2018). DOI: 10.1155/2018/7908764.

A Vermeulen, L Verdonck, and J M Kaufman. “A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum”. The Journal of Clinical Endocrinology & Metabolism 84(10) (1999), pp. 3666–3672. DOI: 10.1210/jcem.84.10.6079.

A Z Jukic, A N Hoofnagle, and Lutsey Pl. “Measurement of Vitamin D for Epidemiologic and Clinical Research: Shining Light on a Complex Decision”. Am J Epidemiol 187(4) (2018), pp. 879–890. DOI: 10.1093/aje/kwx297.

N Z Walli et al. “Vitamin D Levels in Malnourished Children under 5 Years in a Tertiary Care Center at Muhimbili National Hospital, Dar es Salaam, Tanzania—A Cross-sectional Study”. J Trop Pediatr 63(3) (2017), pp. 203–209. DOI: 10.1093/tropej/fmw081.

Daniel Zehnder et al. “Extrarenal Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase”. The Journal of Clinical Endocrinology & Metabolism 86(2) (2001), pp. 888–894. DOI: 10.1210/jcem.86.2.7220.

Yu Zhang et al. “Effects of Vitamin D Supplementation on Prevention of Type 2 Diabetes in Patients With Prediabetes: A Systematic Review and Meta-analysis”. Diabetes Care 43(7) (2020), pp. 1650–1658. DOI: 10.2337/dc19-1708.

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Published

2021-06-29

How to Cite

Subber, Z., Al-Shamma, G., & Hashim, H. (2021). The total and free vitamin D in type 2 diabetes mellitus patients in Baghdad city: Free and total vitamin D. Baghdad Journal of Biochemistry and Applied Biological Sciences, 2(02), 79–93. https://doi.org/10.47419/bjbabs.v2i02.41