Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis

Abstract

In 2007, supplementation with the trace element selenium in a trial was unexpectedly found to be associated with an excess risk of type 2 diabetes. Given the concerns raised by these findings and the large number of recent studies on this topic, we reviewed the available literature with respect to this possible association. In this paper, we assessed the results of both experimental and nonexperimental epidemiologic studies linking selenium with type 2 diabetes incidence. Through a systematic literature search, we retrieved 50 potentially eligible nonexperimental studies and 5 randomized controlled trials published through June 11, 2018. To elucidate the possible dose–response relation, we selected for further analysis those studies that included multiple exposure levels and serum or plasma levels. We computed a pooled summary risk ratio (RR) of diabetes according to selenium exposure in these studies. We also computed a RR for diabetes incidence following supplementation with 200 µg/day of selenium compared with placebo in trials. In the nonexperimental studies, we found a direct relation between selenium exposure and risk of diabetes, with a clear and roughly linear trend in subjects with higher plasma or serum selenium levels, with RR at 140 µg/L of selenium exposure compared with a referent category of < 45 µg/L equal to 3.6 [95% confidence interval (CI) 1.4–9.4]. A dose–response meta-analysis focusing on studies with direct assessment of dietary selenium intake showed a similar trend. In experimental studies, selenium supplementation increased the risk of diabetes by 11% (RR 1.11, 95% CI 1.01–1.22) compared with the placebo-allocated participants, with a higher RR in women than in men. Overall, results from both nonexperimental and experimental studies indicate that selenium may increase the risk of type 2 diabetes across a wide range of exposure levels. The relative increase in risk is small but of possible public health importance because of the high incidence of diabetes and the ubiquity of selenium exposure.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    Vinceti M, Burlingame B, Fillippini T, Naska A, Bargellini A, Borella P. The epidemiology of selenium and human health. In: Hatfield D, Schweizer U, Gladyshev VN, editors. Selenium: its molecular biology and role in human health. 4th ed. New York: Springer Science+Business Media; 2016. p. 365–76.

  2. 2.

    Vinceti M, Crespi CM, Malagoli C, Del Giovane C, Krogh V. Friend or foe? The current epidemiologic evidence on selenium and human cancer risk. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2013;31:305–41.

  3. 3.

    Jablonska E, Vinceti M. Selenium and human health: witnessing a Copernican revolution? J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2015;33:328–68.

  4. 4.

    Fairweather-Tait SJ, Bao Y, Broadley MR, et al. Selenium in human health and disease. Antioxid Redox Signal. 2011;14:1337–83.

  5. 5.

    Vinceti M, Filippini T, Cilloni S, Crespi CM. The epidemiology of selenium and human cancer. Adv Cancer Res. 2017;136:1–48.

  6. 6.

    Vinceti M, Filippini T, Del Giovane C, et al. Selenium for preventing cancer. Cochrane Database Syst Rev. 2018;1:CD005195.

  7. 7.

    Vinceti M, Crespi CM, Bonvicini F, et al. The need for a reassessment of the safe upper limit of selenium in drinking water. Sci Total Environ. 2013;443:633–42.

  8. 8.

    Vinceti M, Dennert G, Crespi CM, et al. Selenium for preventing cancer. Cochrane Database Syst Rev. 2014;3:CD005195.

  9. 9.

    Rees K, Hartley L, Day C, Flowers N, Clarke A, Stranges S. Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:CD009671.

  10. 10.

    Oliveira CS, Piccoli BC, Aschner M, Rocha JBT. Chemical speciation of selenium and mercury as determinant of their neurotoxicity. Adv Neurobiol. 2017;18:53–83.

  11. 11.

    Cicero CE, Mostile G, Vasta R, et al. Metals and neurodegenerative diseases. A systematic review. Environ Res. 2017;159:82–94.

  12. 12.

    Langlois PL, Hardy G, Manzanares W. Pharmaconutrition with intravenous selenium in intensive care: the end of an era? Nutrition. 2018;45:142–4.

  13. 13.

    Winther KH, Bonnema SJ, Hegedus L. Is selenium supplementation in autoimmune thyroid diseases justified? Curr Opin Endocrinol Diabetes Obes. 2017;24:348–55.

  14. 14.

    Kljai K, Runje R. Selenium and glycogen levels in diabetic patients. Biol Trace Elem Res. 2001;83:223–9.

  15. 15.

    Faure P. Protective effects of antioxidant micronutrients (vitamin E, zinc and selenium) in type 2 diabetes mellitus. Clin Chem Lab Med. 2003;41:995–8.

  16. 16.

    Rajpathak S, Rimm E, Morris JS, Hu F. Toenail selenium and cardiovascular disease in men with diabetes. J Am Coll Nutr. 2005;24:250–6.

  17. 17.

    Stranges S, Marshall JR, Natarajan R, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147:217–23.

  18. 18.

    Zhao Z, Barcus M, Kim J, Lum KL, Mills C, Lei XG. High dietary selenium intake alters lipid metabolism and protein synthesis in liver and muscle of pigs. J Nutr. 2016;146:1625–33.

  19. 19.

    Zhou J, Xu G, Bai Z, et al. Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway. Toxicol Appl Pharmacol. 2015;289:409–18.

  20. 20.

    Wang X, Zhang W, Chen H, et al. High selenium impairs hepatic insulin sensitivity through opposite regulation of ROS. Toxicol Lett. 2014;224:16–23.

  21. 21.

    Greenland S, Longnecker MP. Methods for trend estimation from summarized dose–response data, with applications to meta-analysis. Am J Epidemiol. 1992;135:1301–9.

  22. 22.

    Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D. Meta-analysis for linear and nonlinear dose–response relations: examples, an evaluation of approximations, and software. Am J Epidemiol. 2012;175:66–73.

  23. 23.

    Feng W, Cui X, Liu B, et al. Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China. PLoS ONE. 2015;10:e0123742.

  24. 24.

    Wei J, Zeng C, Gong QY, et al. The association between dietary selenium intake and diabetes: a cross-sectional study among middle-aged and older adults. Nutr J. 2015;14:18.

  25. 25.

    Liu B, Feng W, Wang J, et al. Association of urinary metals levels with type 2 diabetes risk in coke oven workers. Environ Pollut. 2016;210:1–8.

  26. 26.

    Su LQ, Jin YL, Unverzagt FW, et al. Nail selenium level and diabetes in older people in rural China. Biomed Environ Sci. 2016;29:818–24.

  27. 27.

    Lu CW, Chang HH, Yang KC, Kuo CS, Lee LT, Huang KC. High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance. BMJ Open Diabetes Res Care. 2016;4:e000253.

  28. 28.

    Vinceti M, Filippini T, Crippa A, de Sesmaisons A, Wise LA, Orsini N. Meta-analysis of potassium intake and the risk of stroke. J Am Heart Assoc. 2016;5:e004210.

  29. 29.

    Pounis G, Costanzo S, Persichillo M, et al. Mushroom and dietary selenium intakes in relation to fasting glucose levels in a free-living Italian adult population: the Moli-sani Project. Diabetes Metab. 2014;40:34–42.

  30. 30.

    Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose–response data. Stata J. 2006;6:40–57.

  31. 31.

    Jackson D, White IR, Thompson SG. Extending DerSimonian and Laird’s methodology to perform multivariate random effects meta-analyses. Stat Med. 2010;29:1282–97.

  32. 32.

    Li XT, Yu PF, Gao Y, et al. Association between plasma metal levels and diabetes risk: a case–control study in China. Biomed Environ Sci. 2017;30:482–91.

  33. 33.

    Lippman SM, Klein EA, Goodman PJ, et al. 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.

  34. 34.

    Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306:1549–56.

  35. 35.

    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

  36. 36.

    Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. http://handbook.cochrane.org.

  37. 37.

    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

  38. 38.

    Schlienger JL, Grunenberger F, Maier EA, Simon C, Chabrier G, Leroy MJ. Disorders of plasma trace elements in diabetes. Relation to blood glucose equilibrium. Presse Med. 1988;17:1076–9.

  39. 39.

    El-Yazigi A, Legayada E. Urinary selenium in healthy and diabetic Saudi Arabians. Biol Trace Elem Res. 1996;52:55–63.

  40. 40.

    Navarro-Alarcon M, de la Serrana HLG, 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.

  41. 41.

    Ekmekcioglu C, Prohaska C, Pomazal K, Steffan I, Schernthaner G, Marktl W. Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls. Biol Trace Elem Res. 2001;79:205–19.

  42. 42.

    Kornhauser C, Garcia-Ramirez JR, Wrobel K, Perez-Luque EL, Garay-Sevilla ME, Wrobel K. Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patients. Prim Care Diabetes. 2008;2:81–5.

  43. 43.

    Whiting PH, Kalansooriya A, Holbrook I, Haddad F, Jennings PE. The relationship between chronic glycaemic control and oxidative stress in type 2 diabetes mellitus. Br J Biomed Sci. 2008;65:71–4.

  44. 44.

    Zhao C, Wang H, Zhang J, Feng L. Correlations of trace elements, glucose and body compositions in type 2 diabetics. Wei Sheng Yan Jiu. 2008;37:600–1.

  45. 45.

    Flores CR, Puga MP, Wrobel K, Garay Sevilla ME, Wrobel K. Trace elements status in diabetes mellitus type 2: possible role of the interaction between molybdenum and copper in the progress of typical complications. Diabetes Res Clin Pract. 2011;91:333–41.

  46. 46.

    Forte G, Bocca B, Peruzzu A, et al. Blood metals concentration in type 1 and type 2 diabetics. Biol Trace Elem Res. 2013;156:79–90.

  47. 47.

    Thomas B, Ramesh A, Suresh S, Prasad BR. A comparative evaluation of antioxidant enzymes and selenium in the serum of periodontitis patients with diabetes mellitus type 2. Contemp Clin Dent. 2013;4:176–80.

  48. 48.

    Yerlikaya FH, Toker A, Aribas A. Serum trace elements in obese women with or without diabetes. Indian J Med Res. 2013;137:339–45.

  49. 49.

    Ubajaka CF, Meludu SC, Dioka CE, et al. Evaluation of male sex hormones and trace elements in male type 2 diabetic patients attending Nnamdi Azikiwe University Teaching Hospital Diabetic Clinics. Niger J Med. 2015;24:162–8.

  50. 50.

    Yin Y, Han W, Wang Y, et al. Identification of risk factors affecting impaired fasting glucose and diabetes in adult patients from Northeast China. Int J Environ Res Public Health. 2015;12:12662–78.

  51. 51.

    Badran M, Morsy R, Soliman H, Elnimr T. Assessment of trace elements levels in patients with type 2 diabetes using multivariate statistical analysis. J Trace Elem Med Biol. 2016;33:114–9.

  52. 52.

    Bolajokol EB, Akinosui OM, Anetor JI, Mossanda KS. Micronutrient status and its effect on glycaemic indices in type 2 diabetics with foot ulcer in Ibadan, Nigeria. Afr J Med Med Sci. 2016;45:83–90.

  53. 53.

    Gonzalez de Vega R, Fernandez-Sanchez ML, Fernandez JC, Alvarez Menendez FV, Sanz-Medel A. Selenium levels and glutathione peroxidase activity in the plasma of patients with type II diabetes mellitus. J Trace Elem Med Biol. 2016;37:44–9.

  54. 54.

    Gouaref I, Bellahsene Z, Zekri S, Alamir B, Koceir EA. The link between trace elements and metabolic syndrome/oxidative stress in essential hypertension with or without type 2 diabetes. Ann Biol Clin (Paris). 2016;74:233–43.

  55. 55.

    Cancarini A, Fostinelli J, Napoli L, Gilberti ME, Apostoli P, Semeraro F. Trace elements and diabetes: assessment of levels in tears and serum. Exp Eye Res. 2017;154:47–52.

  56. 56.

    Hansen AF, Simic A, Asvold BO, et al. Trace elements in early phase type 2 diabetes mellitus—a population-based study. The HUNT study in Norway. J Trace Elem Med Biol. 2017;40:46–53.

  57. 57.

    Simic A, Hansen AF, Asvold BO, et al. Trace element status in patients with type 2 diabetes in Norway: the HUNT3 Survey. J Trace Elem Med Biol. 2017;41:91–8.

  58. 58.

    Skalnaya MG, Skalny AV, Yurasov VV, et al. Serum trace elements and electrolytes are associated with fasting plasma glucose and HbA1c in postmenopausal women with type 2 diabetes mellitus. Biol Trace Elem Res. 2017;177:25–32.

  59. 59.

    Coudray C, Roussel AM, Mainard F, Arnaud J, Favier A. Lipid peroxidation level and antioxidant micronutrient status in a pre-aging population; correlation with chronic disease prevalence in a French epidemiological study (Nantes, France). J Am Coll Nutr. 1997;16:584–91.

  60. 60.

    Hughes K, Choo M, Kuperan P, Ong CN, Aw TC. Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore. Atherosclerosis. 1998;136:25–31.

  61. 61.

    Bleys J, Navas-Acien A, Guallar E. Serum selenium and diabetes in U.S. adults. Diabetes Care. 2007;30:829–34.

  62. 62.

    Gao S, Jin Y, Hall KS, et al. Selenium level and cognitive function in rural elderly Chinese. Am J Epidemiol. 2007;165:955–65.

  63. 63.

    Li N, Gao Z, Luo D, Tang X, Chen D, Hu Y. Selenium level in the environment and the population of Zhoukoudian area, Beijing, China. Sci Total Environ. 2007;381:105–11.

  64. 64.

    Laclaustra M, Navas-Acien A, Stranges S, Ordovas JM, Guallar E. Serum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003–2004. Environ Health Perspect. 2009;117:1409–13.

  65. 65.

    Yang KC, Lee LT, Lee YS, Huang HY, Chen CY, Huang KC. Serum selenium concentration is associated with metabolic factors in the elderly: a cross-sectional study. Nutr Metab (Lond). 2010;7:38.

  66. 66.

    Stranges S, Galletti F, Farinaro E, et al. Associations of selenium status with cardiometabolic risk factors: an 8-year follow-up analysis of the Olivetti Heart study. Atherosclerosis. 2011;217:274–8.

  67. 67.

    Dai H, Chen LY, Li SQ. Prevalence of diabetes and impaired glucose regulation in Chengdu populations and associated dietary risk factors. Sichuan Da Xue Xue Bao Yi Xue Ban. 2014;45:79–83.

  68. 68.

    Rotter I, Kosik-Bogacka D, Dolegowska B, Safranow K, Lubkowska A, Laszczynska M. Relationship between the concentrations of heavy metals and bioelements in aging men with metabolic syndrome. Int J Environ Res Public Health. 2015;12:3944–61.

  69. 69.

    Alehagen U, Johansson P, Bjornstedt M, Rosen A, Post C, Aaseth J. Relatively high mortality risk in elderly Swedish subjects with low selenium status. Eur J Clin Nutr. 2016;70:91–6.

  70. 70.

    Galan-Chilet I, Grau-Perez M, De Marco G, et al. A gene-environment interaction analysis of plasma selenium with prevalent and incident diabetes: the Hortega study. Redox Biol. 2017;12:798–805.

  71. 71.

    Zhang H, Yan C, Yang Z, et al. Alterations of serum trace elements in patients with type 2 diabetes. J Trace Elem Med Biol. 2017;40:91–6.

  72. 72.

    Xiao L, Zhou Y, Ma J, et al. Oxidative DNA damage mediates the association between urinary metals and prevalence of type 2 diabetes mellitus in Chinese adults. Sci Total Environ. 2018;627:1327–33.

  73. 73.

    He K, Liu K, Morris SJ, et al. Longitudinal association of toenail selenium levels with incidence of type 2 diabetes: 18-year follow-up of the CARDIA Trace Element Study. Circulation. 2009;119:e300.

  74. 74.

    Stranges S, Sieri S, Vinceti M, et al. A prospective study of dietary selenium intake and risk of type 2 diabetes. BMC Public Health. 2010;10:564.

  75. 75.

    Park K, Rimm EB, Siscovick DS, et al. Toenail selenium and incidence of type 2 diabetes in U.S. men and women. Diabetes Care. 2012;35:1544–51.

  76. 76.

    Gao H, Hagg S, Sjogren P, Lambert PC, Ingelsson E, van Dam RM. Serum selenium in relation to measures of glucose metabolism and incidence of Type 2 diabetes in an older Swedish population. Diabet Med. 2014;31:787–93.

  77. 77.

    Vinceti M, Grioni S, Alber D, et al. Toenail selenium and risk of type 2 diabetes: the ORDET cohort study. J Trace Elem Med Biol. 2015;29:145–50.

  78. 78.

    Yuan Y, Xiao Y, Yu Y, et al. Associations of multiple plasma metals with incident type 2 diabetes in Chinese adults: the Dongfeng–Tongji Cohort. Environ Pollut. 2018;237:917–25.

  79. 79.

    Karp DD, Lee SJ, Keller SM, et al. Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597. J Clin Oncol. 2013;31:4179–87.

  80. 80.

    Algotar AM, Hsu CH, Singh P, Stratton SP. Selenium supplementation has no effect on serum glucose levels in men at high risk of prostate cancer. J Diabetes. 2013;5:465–70.

  81. 81.

    Thompson PA, Ashbeck EL, Roe DJ, et al. Selenium supplementation for prevention of colorectal adenomas and risk of associated type 2 diabetes. J Natl Cancer Inst. 2016;108:djw152.

  82. 82.

    Algotar AM, Stratton MS, Ahmann FR, et al. Phase 3 clinical trial investigating the effect of selenium supplementation in men at high-risk for prostate cancer. Prostate. 2013;73:328–35.

  83. 83.

    Wang XL, Yang TB, Wei J, Lei GH, Zeng C. Association between serum selenium level and type 2 diabetes mellitus: a non-linear dose–response meta-analysis of observational studies. Nutr J. 2016;15:48.

  84. 84.

    Vinceti M, Maraldi T, Bergomi M, Malagoli C. Risk of chronic low-dose selenium overexposure in humans: insights from epidemiology and biochemistry. Rev Environ Health. 2009;24:231–48.

  85. 85.

    Vinceti M, Filippini T, Cilloni S, et al. Health risk assessment of environmental selenium: emerging evidence and challenges. Mol Med Rep. 2017;15:3323–35.

  86. 86.

    Kristal AR, Darke AK, Morris JS, et al. Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk. J Natl Cancer Inst. 2014;106:djt456.

  87. 87.

    Su L, Jin Y, Unverzagt FW, et al. Longitudinal association between selenium levels and hypertension in a rural elderly Chinese cohort. J Nutr Health Aging. 2016;20:983–8.

  88. 88.

    Wu W, Jiang S, Zhao Q, et al. Environmental exposure to metals and the risk of hypertension: a cross-sectional study in China. Environ Pollut. 2018;233:670–8.

  89. 89.

    Sun JW, Shu XO, Li HL, et al. Dietary selenium intake and mortality in two population-based cohort studies of 133 957 Chinese men and women. Public Health Nutr. 2016;19:2991–8.

  90. 90.

    Berthold HK, Michalke B, Krone W, Guallar E, Gouni-Berthold I. Influence of serum selenium concentrations on hypertension: the Lipid Analytic Cologne cross-sectional study. J Hypertens. 2012;30:1328–35.

  91. 91.

    Vinceti M, Grill P, Malagoli C, et al. Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study. J Trace Elem Med Biol. 2015;31:1–10.

  92. 92.

    Clark LC, Combs GFJ, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 1996;276:1957–63.

  93. 93.

    Rayman MP. Food-chain selenium and human health: emphasis on intake. Br J Nutr. 2008;100:254–68.

  94. 94.

    Fan A, Vinceti M. Selenium and its compunds. In: John Wiley & Sons I, editor. Hamilton and Hardy’s industrial toxicology. 6th ed. Hoboken: Wiley; 2015.

  95. 95.

    Vinceti M, Chiari A, Eichmuller M, et al. A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment. Alzheimers Res Ther. 2017;9:100.

  96. 96.

    Lubinski J, Jaworska K, Durda K, et al. Selenium and the risk of cancer in BRCA1 carriers. Hered Cancer Clin Pract. 2011;9:A5.

  97. 97.

    Vinceti M, Solovyev N, Mandrioli J, et al. Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite. Neurotoxicology. 2013;38:25–32.

  98. 98.

    Weekley CM, Harris HH. Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. Chem Soc Rev. 2013;42:8870–94.

  99. 99.

    Michalke B, Willkommena D, Drobyshevb E, Solovyev N. The importance of speciation analysis in neurodegeneration research. Trends Anal Chem. 2018;104:160–70.

  100. 100.

    Labunskyy VM, Lee BC, Handy DE, Loscalzo J, Hatfield DL, Gladyshev VN. Both maximal expression of selenoproteins and selenoprotein deficiency can promote development of type 2 diabetes-like phenotype in mice. Antioxid Redox Signal. 2011;14:2327–36.

  101. 101.

    Rocourt CR, Cheng WH. Selenium supranutrition: are the potential benefits of chemoprevention outweighed by the promotion of diabetes and insulin resistance? Nutrients. 2013;5:1349–65.

  102. 102.

    Ogawa-Wong AN, Berry MJ, Seale LA. Selenium and metabolic disorders: an emphasis on type 2 diabetes risk. Nutrients. 2016;8:80.

  103. 103.

    Jablonska E, Reszka E, Gromadzinska J, et al. The effect of selenium supplementation on glucose homeostasis and the expression of genes related to glucose metabolism. Nutrients. 2016;8:E772.

  104. 104.

    Steinbrenner H. Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism. Free Radic Biol Med. 2013;65:1538–47.

  105. 105.

    Zhou J, Huang K, Lei XG. Selenium and diabetes–evidence from animal studies. Free Radic Biol Med. 2013;65:1548–56.

  106. 106.

    Ishikura K, Misu H, Kumazaki M, et al. Selenoprotein P as a diabetes-associated hepatokine that impairs angiogenesis by inducing VEGF resistance in vascular endothelial cells. Diabetologia. 2014;57:1968–76.

  107. 107.

    Misu H, Takamura T, Takayama H, et al. A liver-derived secretory protein, selenoprotein P, causes insulin resistance. Cell Metab. 2010;12:483–95.

  108. 108.

    Zeng M-S, Li X, Liu Y, et al. A high-selenium diet induces insulin resistance in gestating rats and their offspring. Free Radic Biol Med. 2012;52:1335–42.

  109. 109.

    Pinto A, Speckmann B, Heisler M, Sies H, Steinbrenner H. Delaying of insulin signal transduction in skeletal muscle cells by selenium compounds. J Inorg Biochem. 2011;105:812–20.

  110. 110.

    McClung JP, Roneker CA, Mu W, et al. Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. Proc Natl Acad Sci USA. 2004;101:8852–7.

  111. 111.

    Mita Y, Nakayama K, Inari S, et al. Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models. Nat Commun. 2017;8:1658.

  112. 112.

    Murano K, Ogino H, Okuno T, Arakawa T, Ueno H. Role of supplementary selenium on the induction of insulin resistance and oxidative stress in NSY mice ded a high fat diet. Biol Pharm Bull. 2018;41:92–8.

  113. 113.

    Hatfield D, Carlson BA, Tsuji P, Tobe R, Gladyshev VN. Selenium and cancer. In: Collins JF, editor. Molecular, genetic, and nutritional aspects of major and trace minerals. Amsterdam: Academic Press, Elsevier; 2016.

  114. 114.

    Tsuji PA, Carlson BA, Yoo MH, et al. The 15 kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways. PLoS ONE. 2015;10:e0124487.

  115. 115.

    Hatfield DL, Tsuji PA, Carlson BA, Gladyshev VN. Selenium and selenocysteine: roles in cancer, health, and development. Trends Biochem Sci. 2014;39:112–20.

Download references

Author information

Correspondence to Marco Vinceti.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vinceti, M., Filippini, T. & Rothman, K.J. Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Epidemiol 33, 789–810 (2018). https://doi.org/10.1007/s10654-018-0422-8

Download citation

Keywords

  • Selenium
  • Type 2 diabetes
  • Systematic review
  • Meta-analysis
  • Epidemiology