Download PDF
CC BY-NC-ND 4.0 · J Lab Physicians 2022; 14(02): 190-196
DOI: 10.1055/s-0041-1742285
Original Article

Attenuation of Oxidative Stress, Interleukin-6, High-Sensitivity C-Reactive Protein, Plasminogen Activator Inhibitor-1, and Fibrinogen with Oral Vitamin D Supplementation in Patients with T2DM having Vitamin D Deficiency

Pullaiah Pasupuleti
1   Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
,
M.M. Suchitra
1   Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
,
Aparna R. Bitla
1   Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
,
Alok Sachan
2   Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
› Author Affiliations Funding This work was supported by the University Grants Commission-National Fellowship for Higher Education (UGC-NFHE)-2629, New Delhi and Sri Balaji Aarogya Vara Prasadini Scheme of Sri Venkateswara Institute of Medical Sciences, Tirupati.
› Further Information
   Permissions and Reprints

Abstract

Objectives Type 2 diabetes mellitus (T2DM) associated with oxidative stress and inflammation causes endothelial dysfunction, which promotes cardiovascular risk. Vitamin D with its pleiotropic effect is said to protect against cardiovascular risk. However, with vitamin D deficiency being more prevalent in T2DM, the cardiovascular risk may get compounded.

Materials and Methods An interventional study was conducted on 100 patients with T2DM having vitamin D deficiency (vitamin D < 20 ng/mL), who were given oral supplementation of 2,000 IU/day of vitamin D for a period of 6 months. Serum vitamin D, biomarkers of oxidative stress, malondialdehyde (MDA), oxidized LDL (OxLDL), ferric reducing ability of plasma (FRAP), biomarkers of inflammation, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen were measured at baseline and at the end of the third and sixth month of vitamin D supplementation.

Statistical Analysis Repeated measures analysis of variance (ANOVA) was applied for comparison between baseline and third- and sixth-month data after vitamin D supplementation. Linear regression by generalized estimating equations (GEE), which grouped repeated measures for each subject and accounted for correlations that may occur from multiple observations within subjects, was applied.

Results Serum vitamin D levels reached normal levels with a significant decrease in OxLDL, hsCRP, IL-6, PAI-1, and fibrinogen levels, with a significant increase in FRAP (p = 0.001) levels at the end of 6 months of vitamin D supplementation. These changes were observed even after correction with glycemic control (HbA1c). However, a significant decrease in MDA was observed only at the end of the sixth month of vitamin D supplementation. Vitamin D levels showed a significant negative association with Ox-LDL, Hs-CRP, IL-6, PAI-1, and fibrinogen, even after adjusting for BMI and statin use (p = 0.001).

Conclusion Supplementation of vitamin D for a period of 6 months in patients with T2DM having vitamin D deficiency is beneficial in the attenuation of oxidative stress and inflammation.

Keywords

interleukin-6 - oral vitamin D supplementation - oxidative stress - plasminogen activator inhibitor-1 - type 2 diabetes mellitus - vitamin D deficiency


Publication History

Article published online:
31 December 2021

© 2021. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Therond P. Dommages créés aux biomolécules (lipides, protéines, ADN) par le stress oxydant [Oxidative stress and damages to biomolecules (lipids, proteins, DNA)]. Ann Pharm Fr 2006; 64 (06) 383-389 DOI: 10.1016/s0003-4509(06)75333-0. . PMID: 17119467
    CrossrefPubMedGoogle Scholar
  • 2 Yarmolinsky J, Bordin BarbieriN, Weinmann T, Ziegelmann PK, Duncan BB, Inês SchmidtM. Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies. Sci Rep 2016; 6: 17714 DOI: 10.1038/srep17714. . PMID: 26813008; PMCID: PMC4728395
    CrossrefPubMedGoogle Scholar
  • 3 El-Fakhri N, McDevitt H, Shaikh MG, Halsey C, Ahmed SF. Vitamin D and its effects on glucose homeostasis, cardiovascular function and immune function. Horm Res Paediatr 2014; 81 (06) 363-378
    CrossrefPubMedGoogle Scholar
  • 4 Al-Sofiani ME, Jammah A, Racz M. et al. Effect of vitamin D supplementation on glucose control and inflammatory response in type II diabetes: a double blind, randomized clinical trial. Int J Endocrinol Metab 2015; 13 (01) e22604
    PubMedGoogle Scholar
  • 5 Holick MF. Vitamin D: a d-lightful solution for health. J Investig Med 2011; 59 (06) 872-880
    CrossrefPubMedGoogle Scholar
  • 6 Amer M, Qayyum R. Relation between serum 25-hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol 2012; 109 (02) 226-230
    CrossrefPubMedGoogle Scholar
  • 7 Kassi E, Adamopoulos C, Basdra EK, Papavassiliou AG. Role of vitamin D in atherosclerosis. Circulation 2013; 128 (23) 2517-2531
    CrossrefPubMedGoogle Scholar
  • 8 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 (01) 8 DOI: 10.1186/1758-5996-5-8.
    CrossrefPubMedGoogle Scholar
  • 9 Kumar A, Goel MK, Jain RB, Khanna P, Chaudhary V. India towards diabetes control: key issues. Australas Med J 2013; 6 (10) 524-531
    CrossrefPubMedGoogle Scholar
  • 10 Giri R, Verma R, Jain A, Srivastava V. Status of vitamin D3 level and its co-relation with the glycaemic status in Indian population. Int J Adv Med 2017; 4 (04) 1067-1072 DOI: 10.18203/2349-3933.ijam20173233.
    CrossrefGoogle Scholar
  • 11 Bhatt SP, Misra A, Gulati S, Singh N, Pandey RM. Lower vitamin D levels are associated with higher blood glucose levels in Asian Indian women with pre-diabetes: a population-based cross-sectional study in North India. BMJ Open Diabetes Res Care 2018; 6 (01) e000501
    CrossrefPubMedGoogle Scholar
  • 12 Griz LHM, Bandeira F, Gabbay MAL, Dib SA, Carvalho EF. Vitamin D and diabetes mellitus: an update 2013. Arq Bras Endocrinol Metabol 2014; 58 (01) 1-8
    CrossrefPubMedGoogle Scholar
  • 13 Sánchez-Hernández RM, García-Cantón C, Lorenzo DL. et al. The specific relationship between vitamin D deficiency and diabetic nephropathy among patients with advanced chronic kidney disease: a cross-sectional study in Gran Canaria, Spain. Clin Nephrol 2015; 83 (04) 218-224
    CrossrefPubMedGoogle Scholar
  • 14 Nitsa A, Toutouza M, Machairas N, Mariolis A, Philippou A, Koutsilieris M. Vitamin D in cardiovascular disease. In Vivo 2018; 32 (05) 977-981
    CrossrefPubMedGoogle Scholar
  • 15 Badawi A, Garcia-Bailo B, Arora P. et al. The utility of vitamins in the prevention of type 2 diabetes mellitus and its complications: a public health perspective. In: Oluwafemi Oguntibeju. ed. Diabetes Mellitus - Insights and Perspective. London: IntechOpen Limited; 2013. DOI: 10.5772/47834
    CrossrefGoogle Scholar
  • 16 Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med 2008; 25 (03) 320-325
    CrossrefPubMedGoogle Scholar
  • 17 Shab-Bidar S, Neyestani TR, Djazayery A. Efficacy of vitamin D3-fortified-yogurt drink on anthropometric, metabolic, inflammatory and oxidative stress biomarkers according to vitamin D receptor gene polymorphisms in type 2 diabetic patients: a study protocol for a randomized controlled clinical trial. BMC Endocr Disord 2011; 11: 12 DOI: 10.1186/1472-6823-11-12.
    CrossrefPubMedGoogle Scholar
  • 18 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 (06) 2017-2029
    Google Scholar
  • 19 Ghavamzadeh S, Mobasseri M, Mahdavi R. The effect of vitamin D supplementation on adiposity, blood glycated hemoglobin, serum leptin and tumor necrosis factor-α in type 2 diabetic patients. Int J Prev Med 2014; 5 (09) 1091-1098
    PubMedGoogle Scholar
  • 20 Neyestani TR, Nikooyeh B, Alavi-Majd H. 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 2012; 97 (06) 2005-2011
    CrossrefPubMedGoogle Scholar
  • 21 Witham MD, Dove FJ, Khan F, Lang CC, Belch JJ, Struthers AD. Effects of vitamin D supplementation on markers of vascular function after myocardial infarction–a randomised controlled trial. Int J Cardiol 2013; 167 (03) 745-749
    CrossrefPubMedGoogle Scholar
  • 22 Yiu YF, Yiu KH, Siu CW. et al. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Atherosclerosis 2013; 227 (01) 140-146
    CrossrefPubMedGoogle Scholar
  • 23 Rodriguez AJ, Mousa A, Ebeling PR, Scott D, de Courten B. Effects of vitamin D supplementation on inflammatory markers in heart failure: a systematic review and meta-analysis of randomized controlled trials. Sci Rep 2018; 8 (01) 1169 DOI: 10.1038/s41598-018-19708-0.
    CrossrefPubMedGoogle Scholar
  • 24 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 (1, Suppl 1) S62-S69
    CrossrefPubMedGoogle Scholar
  • 25 Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 2009; 19 (02) 73-78
    CrossrefPubMedGoogle Scholar
  • 26 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95 (02) 351-358
    CrossrefPubMedGoogle Scholar
  • 27 Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 1996; 239 (01) 70-76
    CrossrefPubMedGoogle Scholar
  • 28 Anandabaskar N, Selvarajan S, Dkhar SA, Kamalanathan SK, Tamilarasu K, Bobby Z. Effect of vitamin D supplementation on vascular functions and oxidative stress in type 2 diabetic patients with vitamin D deficiency. Indian J Endocrinol Metab 2017; 21 (04) 555-563
    CrossrefPubMedGoogle Scholar
  • 29 Mansournia MA, Ostadmohammadi V, Doosti-Irani A. et al. The effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res 2018; 50 (06) 429-440
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Zhong W, Gu B, Gu Y, Groome LJ, Sun J, Wang Y. Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells. J Steroid Biochem Mol Biol 2014; 140: 56-62
    CrossrefPubMedGoogle Scholar
  • 31 Labudzynskyi DO, Zaitseva OV, Latyshko NV, Gudkova OO, Veliky MM. Vitamin D3 contribution to the regulation of oxidative metabolism in the liver of diabetic mice. Ukr Biochem J 2015; 87 (03) 75-90
    CrossrefPubMedGoogle Scholar
  • 32 Kanikarla-Marie P, Jain SK. 1,25(OH)2D3 inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis). J Steroid Biochem Mol Biol 2016; 159: 94-101
    CrossrefPubMedGoogle Scholar
  • 33 Görlach A, Brandes RP, Nguyen K, Amidi M, Dehghani F, Busse R. A gp91phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circ Res 2000; 87 (01) 26-32
    CrossrefPubMedGoogle Scholar
  • 34 Zheng N, Shi X, Chen X, Lv W. Associations between inflammatory markers, hemostatic markers, and microvascular complications in 182 Chinese patients with type 2 diabetes mellitus. Lab Med 2015; 46 (03) 214-220
    CrossrefPubMedGoogle Scholar
  • 35 Chen N, Wan Z, Han SF, Li BY, Zhang ZL, Qin LQ. Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials. Nutrients 2014; 6 (06) 2206-2216
    CrossrefPubMedGoogle Scholar
  • 36 Riek AE, Oh J, Bernal-Mizrachi C. Vitamin D regulates macrophage cholesterol metabolism in diabetes. J Steroid Biochem Mol Biol 2010; 121 (1-2): 430-433
    CrossrefPubMedGoogle Scholar
  • 37 Balagopal PB, de Ferranti SD, Cook S. et al; American Heart Association Committee on Atherosclerosis Hypertension and Obesity in Youth of the Council on Cardiovascular Disease in the Young, Council on Nutrition, Physical Activity and Metabolism, Council on Epidemiology and Prevention. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association. Circulation 2011; 123 (23) 2749-2769
    CrossrefPubMedGoogle Scholar