Horm Metab Res 2018; 50(01): 50-55
DOI: 10.1055/s-0043-119221
Endocrine Care

Clinical Trial on the Effects of Vitamin D Supplementation on Metabolic Profiles in Diabetic Hemodialysis

Mohammad Reza Tamadon
1   Department of Internal Medicine, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
,
Alireza Soleimani
2   Department of Internal Medicine, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
,
Fariba Keneshlou
3   Department of Urology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
,
Malihe Zarrati Mojarrad
4   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
,
Fereshteh Bahmani
4   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
,
Afshin Naseri
4   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
,
Hamed Haddad Kashani
5   Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
,
Elahe Seyed Hosseini
5   Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
,
Zatollah Asemi
4   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
› Author Affiliations

Abstract

The current study was conducted to assess the effects of vitamin D supplementation on insulin metabolism, lipid fractions, biomarkers of inflammation, and oxidative stress in diabetic hemodialysis (HD) patients. This randomized double-blind placebo-controlled clinical trial was carried out among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either oral vitamin D3 supplements at a dosage of 50 000 IU (n=30) or placebo (n=30) every 2 weeks for 12 weeks. After 12 weeks of intervention, subjects who received vitamin D supplements compared with the placebo had significantly decreased serum insulin concentrations (–3.4±3.7 vs. +2.0±4.2 μIU/ml, p<0.001), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (–1.2±1.8 vs. +0.9±2.3, p<0.001), and improved quantitative insulin sensitivity check index (QUICKI) (+0.02±0.03 vs. –0.01±0.02, p<0.001). In addition, compared with the placebo, vitamin D supplementation led to significant reductions in serum high-sensitivity C-reactive protein (hs-CRP) (–1.4±2.5 vs. +1.4±4.8 mg/l, p=0.007), plasma malondialdehyde (MDA) (–0.1±0.2 vs. +0.1±0.2 μmol/l, p=0.009) and a significant increase in plasma total antioxidant capacity (TAC) concentrations (+33.8±56.7 vs. –2.0±74.5 mmol/l, p=0.04). We did not see any significant effect of vitamin D supplementation on lipid profiles and other biomarkers of inflammation and oxidative stress compared with the placebo. Overall, we found that vitamin D supplementation had beneficial effects on serum insulin, HOMA-IR, QUICKI, serum hs-CRP, plasma MDA, and TAC levels among diabetic HD patients for 12 weeks.

Clinical registration:

http://www.irct.ir: IRCT201611155623N92.

Supplementary Material



Publication History

Received: 18 July 2017

Accepted: 30 August 2017

Article published online:
28 September 2017

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Ethier J, Mendelssohn DC, Elder SJ, Hasegawa T, Akizawa T, Akiba T, Canaud BJ, Pisoni RL. Vascular access use and outcomes: An international perspective from the dialysis outcomes and practice patterns study. Nephrol Dial Transplant 2008; 23: 3219-3226
  • 2 Sohrabi Z, Eftekhari MH, Eskandari MH, Rezaeianzadeh A, Sagheb MM. Malnutrition-inflammation score and quality of life in hemodialysis patients: is there any correlation?. Nephrourol Mon 2015; 7: e27445
  • 3 Kotur-Stevuljevic J, Simic-Ogrizovic S, Dopsaj V, Stefanovic A, Vujovic A, Ivanic-Corlomanovic T, Spasic S, Kalimanovska-Spasojevic V, Jelic-Ivanovic Z. A hazardous link between malnutrition, inflammation and oxidative stress in renal patients. Clin Biochem 2012; 45: 1202-1205
  • 4 Sit D, Kadiroglu AK, Yilmaz ME, Kara IH, Isikoglu B. The prevalence of insulin resistance and its relationship between anemia, secondary hyperparathyroidism, inflammation, and cardiac parameters in chronic hemodialysis patients. Ren Fail 2005; 27: 403-407
  • 5 Wang Z, Yu C, Li XH, Deng BQ. The prognostic value of oxidative stress and inflammation in Chinese hemodialysis patients. Ren Fail 2017; 39: 54-58
  • 6 Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 1998; 339: 799-805
  • 7 Cupisti A, Vigo V, Baronti ME, D’Alessandro C, Ghiadoni L, Egidi MF. Vitamin D status and cholecalciferol supplementation in chronic kidney disease patients: An Italian cohort report. Int J Nephrol Renovasc Dis 2015; 8: 151-157
  • 8 de Boer IH. Vitamin D and glucose metabolism in chronic kidney disease. Curr Opin Nephrol Hypertens 2008; 17: 566-572
  • 9 Bhan I, Burnett-Bowie SA, Ye J, Tonelli M, Thadhani R. Clinical measures identify vitamin D deficiency in dialysis. Clin J Am Soc Nephrol 2010; 5: 460-467
  • 10 Mak RH. Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients. Kidney Int 1992; 41: 1049-1054
  • 11 Mak RH. Amelioration of hypertension and insulin resistance by 1,25-dihydroxycholecalciferol in hemodialysis patients. Pediatr Nephrol 1992; 6: 345-348
  • 12 Hung AM, Sundell MB, Plotnikova NE, Bian A, Shintani A, Ellis CD, Siew ED, Ikizler TA. A pilot study of active vitamin D administration and insulin resistance in African American patients undergoing chronic hemodialysis. J Ren Nutr 2013; 23: 185-193
  • 13 Sarathy H, Pramanik V, Kahn J, Abramowitz MK, Meier K, Kishore P, Melamed ML. The effects of short-term vitamin D supplementation on glucose metabolism in dialysis patients: A systematic review and meta-analysis. Int Urol Nephrol 2015; 47: 537-549
  • 14 Farrokhian A, Raygan F, Bahmani F, Talari HR, Esfandiari R, Esmaillzadeh A, Asemi Z. Long-term vitamin D supplementation affects metabolic status in vitamin D-deficient type 2 diabetic patients with coronary artery disease. J Nutr 2017; 147: 384-389
  • 15 Wang H, Xia N, Yang Y, Peng DQ. Influence of vitamin D supplementation on plasma lipid profiles: A meta-analysis of randomized controlled trials. Lipids Health Dis 2012; 11: 42
  • 16 Szeto FL, Sun J, Kong J, Duan Y, Liao A, Madara JL, Li YC. Involvement of the vitamin D receptor in the regulation of NF-kappaB activity in fibroblasts. J Steroid Biochem Mol Biol 2007; 103: 563-566
  • 17 Hamden K, Carreau S, Jamoussi K, Miladi S, Lajmi S, Aloulou D, Ayadi F, Elfeki A. 1Alpha,25 dihydroxyvitamin D3: therapeutic and preventive effects against oxidative stress, hepatic, pancreatic and renal injury in alloxan-induced diabetes in rats. J Nutr Sci Vitaminol (Tokyo) 2009; 55: 215-222
  • 18 Pisprasert V, Ingram KH, Lopez-Davila MF, Munoz AJ, Garvey WT. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: Impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans. Diabetes Care 2013; 36: 845-853
  • 19 Tatsch E, Bochi GV, Pereira Rda S, Kober H, Agertt VA, de Campos MM, Gomes P, Duarte MM, Moresco RN. A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem 2011; 44: 348-350
  • 20 Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 1996; 239: 70-76
  • 21 Beutler E, Gelbart T. Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med 1985; 105: 581-584
  • 22 Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 1990; 9: 515-540
  • 23 Nursal TZ, Noyan T, Tarim A, Karakayali H. A new weighted scoring system for subjective global assessment. Nutrition 2005; 21: 666-671
  • 24 Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 1993; 4: 1205-1213
  • 25 Esteghamati A, Aryan Z, Esteghamati A, Nakhjavani M. Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics. Horm Metab Res 2015; 47: 273-279
  • 26 Shaffi K, Tighiouart H, Scott T, Lou K, Drew D, Weiner D, Sarnak M. Low 25-hydroxyvitamin D levels and cognitive impairment in hemodialysis patients. Clin J Am Soc Nephrol 2013; 8: 979-986
  • 27 Mailliez S, Shahapuni I, Lecaque C, Massy ZA, Choukroun G, Fournier A. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 2008; 74: 389
  • 28 Mak RH. 1,25-Dihydroxyvitamin D3 corrects insulin and lipid abnormalities in uremia. Kidney Int 1998; 53: 1353-1357
  • 29 Strobel F, Reusch J, Penna-Martinez M, Ramos-Lopez E, Klahold E, Klepzig C, Wehrle J, Kahles H, Badenhoop K. Effect of a randomised controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus. Horm Metab Res 2014; 46: 54-58
  • 30 Karamali M, Beihaghi E, Mohammadi AA, Asemi Z. Effects of high-Dose vitamin D supplementation on metabolic status and pregnancy outcomes in pregnant women at risk for pre-eclampsia. Horm Metab Res 2015; 47: 867-872
  • 31 Razavi M, Jamilian M, Karamali M, Bahmani F, Aghadavod E, Asemi Z. The effects of vitamin d-k-calcium co-supplementation on endocrine, inflammation, and oxidative stress biomarkers in vitamin d-deficient women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Horm Metab Res 2016; 48: 446-451
  • 32 Lin SH, Lin YF, Lu KC, Diang LK, Chyr SH, Liao WK, Shieh SD. Effects of intravenous calcitriol on lipid profiles and glucose tolerance in uraemic patients with secondary hyperparathyroidism. Clin Sci (Lond) 1994; 87: 533-538
  • 33 Petchey WG, Hickman IJ, Prins JB, Hawley CM, Johnson DW, Isbel NM, Duncan EL. Vitamin D does not improve the metabolic health of patients with chronic kidney disease stage 3-4: A randomized controlled trial. Nephrology (Carlton) 2013; 18: 26-35
  • 34 Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, Franch H, Guarnieri G, Ikizler TA, Kaysen G, Lindholm B, Massy Z, Mitch W, Pineda E, Stenvinkel P, Treviño-Becerra A, Wanner C. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int 2008; 73: 391-398
  • 35 Shinohara K, Shoji T, Emoto M, Tahara H, Koyama H, Ishimura E, Miki T, Tabata T, Nishizawa Y. Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J Am Soc Nephrol 2002; 13: 1894-1900
  • 36 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: 227-232
  • 37 Sergeev IN, Rhoten WB. 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology 1995; 136: 2852-2861
  • 38 Reid IR. Effects of calcium supplementation on circulating lipids: Potential pharmacoeconomic implications. Drugs Aging 2004; 21: 7-17
  • 39 Rajpathak SN, Xue X, Wassertheil-Smoller S, Van Horn L, Robinson JG, Liu S, Allison M, Martin LW, Ho GY, Rohan TE. Effect of 5 y of calcium plus vitamin D supplementation on change in circulating lipids: results from the Women’s Health Initiative. Am J Clin Nutr 2010; 91: 894-899
  • 40 Gunnarsson O, Indridason OS, Franzson L, Sigurdsson G. Factors associated with elevated or blunted PTH response in vitamin D insufficient adults. J Intern Med 2009; 265: 488-495
  • 41 Dutta D, Mondal SA, Choudhuri S, Maisnam I, Hasanoor Reza AH, Bhattacharya B, Chowdhury S, Mukhopadhyay S. Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: an open label randomized prospective study from Eastern India. Diabetes Res Clin Pract 2014; 103: e18-e23
  • 42 Chandrashekara S, Patted A. Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study. Int J Rheum Dis 2017; 20: 825-831
  • 43 Neyestani TR, Nikooyeh B, Alavi-Majd H, Shariatzadeh N, Kalayi A, Tayebinejad N, Heravifard S, Salekzamani S, Zahedirad M. 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: 2005-2011
  • 44 Razzaghi R, Pourbagheri H, Momen-Heravi M, Bahmani F, Shadi J, Soleimani Z, Asemi Z. The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. J Diabetes Complications 2017; 31: 766-772
  • 45 Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 2009; 94: 4023-4030
  • 46 Foroughi M, Maghsoudi Z, Ghiasvand R, Iraj B, Askari G. Effect of vitamin D supplementation on C-reactive protein in patients with nonalcoholic fatty liver. Int J Prev Med 2014; 5: 969-975
  • 47 den Elzen WP, van Manen JG, Boeschoten EW, Krediet RT, Dekker FW. The effect of single and repeatedly high concentrations of C-reactive protein on cardiovascular and non-cardiovascular mortality in patients starting with dialysis. Nephrol Dial Transplant 2006; 21: 1588-1595
  • 48 Honda H, Qureshi AR, Heimburger O, Barany P, Wang K, Pecoits-Filho R, Stenvinkel P, Lindholm B. Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis 2006; 47: 139-148
  • 49 Taccone-Gallucci M, Noce A, Bertucci P, Fabbri C, Manca-di-Villahermosa S, Della-Rovere FR, De Francesco M, Lonzi M, Federici G, Scaccia F, Dessì M. Chronic treatment with statins increases the availability of selenium in the antioxidant defence systems of hemodialysis patients. J Trace Elem Med Biol 2010; 24: 27-30
  • 50 Struglia M, Stamerra CA, Di Giosia P, Giorgini P, Capanna C, Grassi D, Properzi G, Ferri C. Vitamin d deficiency and endothelial dysfunction in rheumatoid arthritis patients. J Hypertens 2015; 33 (Suppl. 01) e84
  • 51 Jain SK, Micinski D. Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun 2013; 437: 7-11