Horm Metab Res 2016; 48(04): 263-268
DOI: 10.1055/s-0035-1569276
Endocrine Care

Selenium Supplementation Affects Insulin Resistance and Serum hs-CRP in Patients with Type 2 Diabetes and Coronary Heart Disease

A. Farrokhian
1   Department of Cardiology, School of Medicine, Kashan University of Medical Sciences, Kashan, I. R. Iran
F. Bahmani
2   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran
M. Taghizadeh
2   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran
S. M. Mirhashemi
2   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran
MH Aarabi
2   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran
F. Raygan
1   Department of Cardiology, School of Medicine, Kashan University of Medical Sciences, Kashan, I. R. Iran
E. Aghadavod
2   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran
Z. Asemi
2   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran
› Author Affiliations


To our knowledge, this study is the first indicating the effects of selenium supplementation on metabolic status of patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This study was conducted to evaluate the effects of selenium supplementation on metabolic profiles, biomarkers of inflammation, and oxidative stress of patients with T2DM and CHD. This randomized, double-blind, placebo-controlled trial was performed among 60 patients with T2DM and CHD aged 40–85 years. Participants were randomly divided into 2 groups. Group A received 200 μg selenium supplements (n=30) and group B received placebo per day (n=30) for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify metabolic profiles. After 8 weeks, compared with the placebo, selenium supplementation resulted in a significant decrease in serum insulin levels (− 2.2±4.6 vs. + 3.6±8.4 μIU/ml, p=0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (− 0.7±1.3 vs. + 0.9±2.4, p=0.004), homeostatic model assessment-beta cell function (HOMA-B) (− 7.5±17.2 vs. + 15.1±34.5, p=0.002) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (+0.01±0.03 vs. − 0.01±0.03, p=0.02). In addition, patients who received selenium supplements had a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (− 1 372.3±2 318.8 vs. − 99.8±1 453.6 ng/ml, p=0.01) and a significant rise in plasma total antioxidant capacity (TAC) concentrations (+ 301.3±400.6 vs. − 127.2±428.0 mmol/l, p<0.001) compared with the placebo. A 200 μg/day selenium supplementation among patients with T2DM and CHD resulted in a significant decrease in insulin, HOMA-IR, HOMA-B, serum hs-CRP, and a significant increase in QUICKI score and TAC concentrations.

Supporting Information

Publication History

Received: 15 July 2015

Accepted: 11 November 2015

Article published online:
07 January 2016

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Chokrungvaranon N, Deer J, Reaven PD. Intensive glycemic control and cardiovascular disease: are there patients who may benefit?. Postgrad Med 2011; 123: 114-123
  • 2 Rana JS, Dunning A, Achenbach S, Al-Mallah M, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Cheng VY, Chinnaiyan K, Chow BJ, Cury R, Delago A, Feuchtner G, Hadamitzky M, Hausleiter J, Kaufmann P, Karlsberg RP, Kim YJ, Leipsic J, Labounty TM, Lin FY, Maffei E, Raff G, Villines TC, Shaw LJ, Berman DS, Min JK. Differences in prevalence, extent, severity, and prognosis of coronary artery disease among patients with and without diabetes undergoing coronary computed tomography angiography: results from 10,110 individuals from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes): an InteRnational Multicenter Registry. Diabetes Care 2012; 35: 1787-1794
  • 3 Iijima K, Iimuro S, Shinozaki T, Ohashi Y, Sakurai T, Umegaki H, Araki A, Ouchi Y, Ito H. Lower physical activity is a strong predictor of cardiovascular events in elderly patients with type 2 diabetes mellitus beyond traditional risk factors: the Japanese Elderly Diabetes Intervention Trial. Geriatr Gerontol Int 2012; 12 (Suppl. 01) 77-87
  • 4 UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-865
  • 5 Klein EA, Thompson IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011; 306: 1549-1556
  • 6 Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J 2013; 34: 2436-2443
  • 7 von Bibra H, St John Sutton M, Schuster T, Ceriello A, Siegmund T, Schumm-Draeger PM. Oxidative stress after a carbohydrate meal contributes to the deterioration of diastolic cardiac function in nonhypertensive insulin-treated patients with moderately well controlled type 2 diabetes. Horm Metab Res 2013; 45: 449-455
  • 8 Zhang X, Yan SM, Zheng HL, Hu DH, Zhang YT, Guan QH, Ding QL. A mechanism underlying hypertensive occurrence in the metabolic syndrome: cooperative effect of oxidative stress and calcium accumulation in vascular smooth muscle cells. Horm Metab Res 2014; 46: 126-132
  • 9 Das UN. Nutritional factors in the prevention and management of coronary artery disease and heart failure. Nutrition 2015; 31: 283-291
  • 10 Zablocka-Slowinska K, Dzielska E, Gryszkin I, Grajeta H. Dietary supplementation during diabetes therapy and the potential risk of interactions. Adv Clin Exp Med 2014; 23: 939-946
  • 11 Eaton CB, Abdul Baki AR, Waring ME, Roberts MB, Lu B. The association of low selenium and renal insufficiency with coronary heart disease and all-cause mortality: NHANES III follow-up study. Atherosclerosis 2010; 212: 689-694
  • 12 Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E. Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr 2006; 84: 762-773
  • 13 Stranges S, Marshall JR, Trevisan M, Natarajan R, Donahue RP, Combs GF, Farinaro E, Clark LC, Reid ME. Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial. Am J Epidemiol 2006; 163: 694-699
  • 14 Valenta J, Brodska H, Drabek T, Hendl J, Kazda A. High-dose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med 2011; 37: 808-815
  • 15 Jamilian M, Razavi M, Kashan ZF, Ghandi Y, Bagherian T, Asemi Z. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf) 2015; 82: 885-891
  • 16 Alizadeh M, Safaeiyan A, Ostadrahimi A, Estakhri R, Daneghian S, Ghaffari A, Gargari BP. Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial. Ann Nutr Metab 2012; 60: 157-168
  • 17 Li YB, Han JY, Jiang W, Wang J. Selenium inhibits high glucose-induced cyclooxygenase-2 and P-selectin expression in vascular endothelial cells. Mol Biol Rep 2011; 38: 2301-2306
  • 18 He YT, Liu DW, Ding LY, Li Q, Xiao YH. Therapeutic effects and molecular mechanisms of anti-fibrosis herbs and selenium on rats with hepatic fibrosis. World J Gastroenterol 2004; 10: 703-706
  • 19 Welles CC, Whooley MA, Karumanchi SA, Hod T, Thadhani R, Berg AH, Ix JH, Mukamal KJ. Vitamin D deficiency and cardiovascular events in patients with coronary heart disease: data from the Heart and Soul Study. Am J Epidemiol 2014; 179: 1279-1287
  • 20 Jamilian M, Razavi M, Fakhrie Kashan Z, Ghandi Y, Bagherian T, Asemi Z. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf) 2015; 82: 885-891
  • 21 Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, O’Brien WL, Bassett Jr DR, Schmitz KH, Emplaincourt PO, Jacobs Jr DR, Leon AS. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000; 32: S498-S504
  • 22 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
  • 23 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
  • 24 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
  • 25 Beutler E, Gelbart T. Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med 1985; 105: 581-584
  • 26 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
  • 27 Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden 3rd JD, Crawford ED, Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens Jr FL, Baker LH, Coltman Jr CA. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301: 39-51
  • 28 Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, Cappuccio FP, Ceriello A, Reid ME. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med 2007; 147: 217-223
  • 29 Rayman MP, Blundell-Pound G, Pastor-Barriuso R, Guallar E, Steinbrenner H, Stranges S. A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin. PLoS One 2012; 7: e45269
  • 30 Tara F, Maamouri G, Rayman MP, Ghayour-Mobarhan M, Sahebkar A, Yazarlu O, Ouladan S, Tavallaie S, Azimi-Nezhad M, Shakeri MT, Boskabadi H, Oladi M, Sangani MT, Razavi BS, Ferns G. Selenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trial. Taiwan J Obstet Gynecol 2010; 49: 181-187
  • 31 Faghihi T, Radfar M, Barmal M, Amini P, Qorbani M, Abdollahi M, Larijani B. A Randomized, Placebo-Controlled Trial of Selenium Supplementation in Patients With Type 2 Diabetes: Effects on Glucose Homeostasis, Oxidative Stress, and Lipid Profile. Am J Ther 2014; 21: 491-495
  • 32 Brigelius-Flohe R, Banning A, Kny M, Bol GF. Redox events in interleukin-1 signaling. Arch Biochem Biophys 2004; 423: 66-73
  • 33 Douillet C, Tabib A, Bost M, Accominotti M, Borson-Chazot F, Ciavatti M. A selenium supplement associated or not with vitamin E delays early renal lesions in experimental diabetes in rats. Proc Soc Exp Biol Med 1996; 211: 323-331
  • 34 Hwang D, Seo S, Kim Y, Kim C, Shim S, Jee S, Lee S, Jang M, Kim M, Yim S, Lee SK, Kang B, Jang I, Cho J. Selenium acts as an insulin-like molecule for the down-regulation of diabetic symptoms via endoplasmic reticulum stress and insulin signalling proteins in diabetes-induced non-obese diabetic mice. J Biosci 2007; 32: 723-735
  • 35 Navarro-Alarcon M, GdlSH Lopez, Perez-Valero V, Lopez-Martinez C. Serum and urine selenium concentrations as indicators of body status in patients with diabetes mellitus. Sci Total Environ 1999; 228: 79-85
  • 36 Rajpathak S, Rimm E, Morris JS, Hu F. Toenail selenium and cardiovascular disease in men with diabetes. J Am Coll Nutr 2005; 24: 250-256
  • 37 Stapleton SR. Selenium: an insulin-mimetic. Cell Mol Life Sci 2000; 57: 1874-1879
  • 38 Maritim AC, Sanders RA, Watkins 3rd JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003; 17: 24-38
  • 39 Steinbrenner H, Sies H. Protection against reactive oxygen species by selenoproteins. Biochim Biophys Acta 2009; 1790: 1478-1485
  • 40 Jalili M, Kolahi S, Aref-Hosseini SR, Mamegani ME, Hekmatdoost A. Beneficial role of antioxidants on clinical outcomes and erythrocyte antioxidant parameters in rheumatoid arthritis patients. Int J Prev Med 2014; 5: 835-840
  • 41 Razavi M, Jamilian M, Kashan ZF, Heidar Z, Mohseni M, Ghandi Y, Bagherian T, Asemi Z. Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome. Horm Metab Res. 2015 Aug 12, Epub ahead of print
  • 42 Mishra V, Baines M, Perry SE, McLaughlin PJ, Carson J, Wenstone R, Shenkin A. Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. Clin Nutr 2007; 26: 41-50
  • 43 Scheurig AC, Thorand B, Fischer B, Heier M, Koenig W. Association between the intake of vitamins and trace elements from supplements and C-reactive protein: results of the MONICA/KORA Augsburg study. Eur J Clin Nutr 2008; 62: 127-137
  • 44 Dunstan JA, Breckler L, Hale J, Lehmann H, Franklin P, Lyons G, Ching SY, Mori TA, Barden A, Prescott SL. Supplementation with vitamins C, E, beta-carotene and selenium has no effect on anti-oxidant status and immune responses in allergic adults: a randomized controlled trial. Clin Exp Allergy 2007; 37: 180-187
  • 45 Madaric A, Kadrabova J, Krajcovicova-Kudlackova M, Valachovicova M, Spustova V, Mislanova C, Kajaba I, Blazicek P. The effect of bioactive complex of quercetin, selenium, catechins and curcumin on cardiovascular risk markers in healthy population after a two month consumption. Bratisl Lek Listy 2013; 114: 84-87
  • 46 Duntas LH. Selenium and inflammation: underlying anti-inflammatory mechanisms. Horm Metab Res 2009; 41: 443-447
  • 47 Seyedrezazadeh E, Ostadrahimi A, Mahboob S, Assadi Y, Ghaemmagami J, Pourmogaddam M. Effect of vitamin E and selenium supplementation on oxidative stress status in pulmonary tuberculosis patients. Respirology 2008; 13: 294-298
  • 48 Savory LA, Kerr CJ, Whiting P, Finer N, McEneny J, Ashton T. Selenium supplementation and exercise: effect on oxidant stress in overweight adults. Obesity (Silver Spring) 2012; 20: 794-801
  • 49 Ozturk IC, Batcioglu K, Karatas F, Hazneci E, Genc M. Comparison of plasma malondialdehyde, glutathione, glutathione peroxidase, hydroxyproline and selenium levels in patients with vitiligo and healthy controls. Indian J Dermatol 2008; 53: 106-110
  • 50 Rohr-Udilova N, Sieghart W, Eferl R, Stoiber D, Bjorkhem-Bergman L, Eriksson LC, Stolze K, Hayden H, Keppler B, Sagmeister S, Grasl-Kraupp B, Schulte-Hermann R, Peck-Radosavljevic M. Antagonistic effects of selenium and lipid peroxides on growth control in early hepatocellular carcinoma. Hepatology 2012; 55: 1112-1121
  • 51 Zeng J, Zhou J, Huang K. Effect of selenium on pancreatic proinflammatory cytokines in streptozotocin-induced diabetic mice. J Nutr Biochem 2009; 20: 530-536