Abstract
The prevalence of gestational diabetes mellitus (GDM) has increased over the recent decades. Exposure to environmental contaminants may be a risk factor for the development of GDM, but this is heavily dependent on particular circumstances. Studies on various areas linking various factors are therefore needed. We examined the associations between serum trace element levels and incidents of GDM among 102 pregnant women (diabetic n = 60 and healthy n = 42) living in Birjand (Iran). Blood serum samples were analyzed for concentrations of elements linked to particulate matter air pollution such as As, Cd, Cu, Hg, Mn, Ni, V, and Zn. Concentrations of As (8.58 vs. 3.15 μg/L), Cd (6.74 vs. 0.52 μg/L), and Hg (2.60 vs. 0.90 μg/L) were significantly higher in women with GDM. Risk difference (RD) estimation showed that As, 0.516 (0.355, 0.677); Cd, 0.719 (0.534, 0.904); and Hg, 0.505 (0.276, 0.735) increase GDM probability, while V lower that risk, −0.139 (−0.237, −0.042). With the principal component analysis, we were able to separate subjects according to their GDM status based on element levels. Such classification revealed very high efficiency with a true positive rate of 93%, according to linear discriminant analysis. GDM subjects presented higher levels of As, Cd, and Hg, indicating that these elements may disturb insulin metabolism and promote the development of GDM. Therefore, we conclude that systematic monitoring of trace elements followed by multivariate modeling in women planning pregnancy should be carried out to prevent the development of GDM.
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References
Ahyayauch H, García-Arribas AB, Sot J, González-Ramírez EJ, Busto JV, Monasterio BG, Jiménez-Rojo N, Contreras FX, Rendón-Ramírez A, Martin C, Alonso A, Goñi FM (2018) Pb (II) induces scramblase activation and ceramide-domain generation in red blood cells. Sci Report 8:7456. https://doi.org/10.1038/s41598-018-25905-8
Altarelli M, Ben-Hamouda N, Schneider A, Berger MM (2019) Copper deficiency: causes, manifestations, and treatment. Nutr Clin Pract 34:504–513. https://doi.org/10.1002/ncp.10328
American Diabetes Association (2015) Classification and diagnosis of diabetes. In: Diabetes Care 38(Suppl):8–16
Amirabadizadeh A, Nakhaee S, Mehrpour O (2020) Risk assessment of elevated blood lead concentrations in the adult population using a decision tree approach. Drug Chem Toxicol 26:1–8. https://doi.org/10.1080/01480545.2020.1783286
Barret JR (2009) Mother load: arsenic may contribute to gestational diabetes. Environ Health Perspect 117(7):310. https://doi.org/10.1289/ehp.117-a310b
Bensen B, Sudha M, Venkateswaramurthy N, Sambathkumar R (2017) Impact of environmental factors as an etiology for diabetes mellitus. J Pharmaceutical Sci Res 9(11):2029–2032
Buescher JJ, Bland H (2011) Care of the newborn. In: Textbook of Family Medicine E-book. Elsevier, Philadelphia, USA, p 415
Casteleyn L, Dumez B, Becker K, Kolossa-Gehring M, den Hond E, Schoeters G, Castaño A, Koch HM, Angerer J, Esteban M, Exley K, Sepai O, Bloemen L, Horvat M, Knudsen LE, Joas A, Joas R, Biot P, Koppen G, Dewolf MC, Katsonouri A, Hadjipanayis A, Cerná M, Krsková A, Schwedler G, Fiddicke U, Nielsen JKS, Jensen JF, Rudnai P, Közepésy S, Mulcahy M, Mannion R, Gutleb AC, Fischer ME, Ligocka D, Jakubowski M, Reis MF, Namorado S, Lupsa IR, Gurzau AE, Halzlova K, Jajcaj M, Mazej D, Tratnik Snoj J, Posada M, López E, Berglund M, Larsson K, Lehmann A, Crettaz P, Aerts D (2015) A pilot study on the feasibility of European harmonized human biomonitoring: strategies towards a common approach, challenges and opportunities. Environ Res 141:3–14. https://doi.org/10.1016/j.envres.2014.10.028
Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH (2006) The role of phosphoinositide 3-kinase/Akt signaling in low-dose mercury-induced mouse pancreatic beta-cells dysfunction in vitro and in-vivo. Diabetes 55(6):1614–1624. https://doi.org/10.2337/db06-0029
Davenport E, Rad S, Turner A, Fong A, Sugiyama N, Pan D, Ogunyemi D (2014) Are there independent associations between gestational diabetes and heavy metals and industrial chemicals exposure? Am J Obstet Gynecol 2014:194. https://doi.org/10.1016/j.ajog.2013.10.417
Diaz-Villaseñor A, Burns AL, Hiriart M, Cebrián ME, Ostrosky-Wegman P (2007) Arsenic-induced alterations in the expression of genes related to type 2 diabetes mellitus. Toxicol Appl Pharmacol 225(2):123–133. https://doi.org/10.1016/j.taap.2007.08.019
DiSilvestro RA (2000) Zinc in relation to diabetes and oxidative disease. J Nutr 130:1509–1511. https://doi.org/10.1093/jn/130.5.1509S
Ditzenberger GR (2018) Carbohydrates, fat and protein metabolism. In: Maternal, Fetal and Neonatal Physiology – E-book: A Clinical Perspectives. Elsevier, Missouri, USA, p 551
Edwards J, Ackerman C (2016) A review of diabetes mellitus and exposure to the environmental toxicant cadmium with an emphasis on likely mechanisms of action. Curr Diabetes Rev 12:252–258. https://doi.org/10.2174/1573399811666150812142922
Environmental Public Health Services Canada (2008) Chemical biomonitoring in serum of pregnant women in Alberta (2005). Available online: https://open.alberta.ca/dataset/c5158a5c-b550-4ece-ab5e-86166c91738a/resource/424b3749-2f3a-4f71-9aaf-5a71be7038df/download/chemical-biomonitoring-2008.pdf Last access: 5th March 2021.
EPA (2010) An overview of airborne metals regulations, exposure limits, health effects, and contemporary research (appendix C).
Ettinger AS, Zota AR, Amarasiriwardena CJ, Hopkins MR, Schwartz J, Hu H, Wright RO (2009) Maternal arsenic exposure and impaired glucose tolerance during pregnancy. Environ Health Perspect 117(7):1059–1064. https://doi.org/10.1289/ehp0800533
Farnia V, Pirsaheb M, Azadi NA, Mansouri B, Radmehr F (2021) Blood lead concentration among oral/inhaled opium users: systematic review and meta-analysis. Crit Rev Toxicol 51:24–35. https://doi.org/10.1080/10408444.2020.1864722
Furlong CE, Suzuki SM, Stevens RC, Marsillach J, Richter RJ, Jarvik GP, Checkoway H, Samii A, Costa LG, Griffith A, Roberts JW, Yearout D, Zabetian CP (2010) Human PON1, a biomarker of risk of disease and exposure. Chem Biol Interact 187(1–3):355–361. https://doi.org/10.1016/j.cbi.2010.03.033
Gambling L, Kennedy C, McArdle HJ (2011) Iron and copper in fetal development. Semin Cell Dev Biol 22:637–644. https://doi.org/10.1016/j.semcdb.2011.08.011
Genova M, Atanasova B, Ivanova I, Todorova K, Svinarov D (2018) Trace elements and vitamin D in gestational diabetes. Acta Medica Bulgarica 45:45–49. https://doi.org/10.2478/amb-2018-0009
Golozar A, Khademi H, Kamangar F, Poutschi H, Islami F, Abnet CC, Freedman ND, Taylor PR, Pharoah P, Boffetta P, Brennan PJ, Dawsey SM, Malekzadeh R, Etemadi A (2011) Diabetes mellitus and its correlates in an Iranian adult population. PLoS One 6(10):e26725. https://doi.org/10.1371/journal.pone.0026725
Günther T (2010) The biochemical function of Mg2+ in insulin secretion, insulin signal transduction and insulin resistance. Magnes Res 23(1):5–18. https://doi.org/10.1684/mrh.2009.0195
He K, Xun P, Liu K, Morris S, Reis J, Guallard E (2013) Mercury exposure in young adulthood and incidence of diabetes later in life. Diabetes Care 36:1584–1589. https://doi.org/10.2337/dc12-1842
Janicka M, Binkowski LJ, Błaszczyk M, Paluch J, Wojtaś W, Massanyi P, Stawarz R (2014) Cadmium, lead and mercury concentrations and their influence on morphological parameters in blood donors from different age groups from southern Poland. J Trace Elem Med Biol 29:342–346. https://doi.org/10.1016/j.jtemb.2014.10.002
Karamali M, Heidarzadeh Z, Seifati SM, Samimi M, Tabassi Z, Talaee N, Bahardoost H, Asemi Z (2016) Zinc supplementation and the effects on pregnancy outcomes in gestational diabetes: a randomized, double-blind, placebo-controlled trial. Exp Clin Endocrinol Diabetes 124:28–33. https://doi.org/10.1055/s-0035-1564146
Koh ES, Kim SJ, Yoon HE, Chung JH, Chung S, Park CW, Chang YS, Shin SJ (2014) Association of blood manganese level with diabetes and renal dysfunction: a cross-sectional study of Korean general population. BMC Endocrine Disorders 14:24–31. https://doi.org/10.1186/1472-6823-14-24
Kozikowska I, Binkowski LJ, Szczepańska K, Sławska H, Miszczuk K, Śliwińska M, Łaciak T, Stawarz R (2013) Mercury concentrations in human placenta, umbilical cord, cord blood and amniotic fluid and their relation with body parameters of newborns. Environ Pollut 182:256–262. https://doi.org/10.1016/j.envpol.2013.07.030
Kumar S, Trivedi AV (2016) A review on role of nickel in the biological system. Int J Curr Microbiol App Sci 5:719–727. https://doi.org/10.20546/ijcmas.2016.503.084
Lavery JA, Friedman AM, Keyes KM, Wright JD, Ananth CV (2017) Gestational diabetes in the United States: temporal changes in prevalence rates between 1979 and 2010. BJOG Int J Obstet Gynaecol 124:804–813. https://doi.org/10.1111/1471-0528.14236
Li H, Qian X, Wang Q (2013) Heavy metals in atmospheric particulate matter: a comprehensive understanding is needed for monitoring and risk mitigation. Environ Sci Technol 47:13210–13211. https://doi.org/10.1021/es404751a
Li P, Yin J, Zhu Y, Li S, Chen S, Sun T, Shan Z, Wang J, Shang Q, Li X, Yang W, Liu L (2019) Association between plasma concentration of copper and gestational diabetes mellitus. Clin Nutr 38(6):2922–2927. https://doi.org/10.1016/j.clnu.2018.12.032
Liu L, Kauri LM, Mahmud M, Weichenthal S, Cakmak S, Shutt R, You H, Thomson E, Vincent R, Kumarathasan P, Broad G, Dales R (2013) Exposure to air pollution near a steel plant and effects on cardiovascular physiology: a randomized crossover study. Int J Hyg Environ Health 217:279–286. https://doi.org/10.1016/j.ijheh.2013.06.007
Liu L, Zhang Y, Pioa J, Mao D, Li Y, Li W, Yang L, Yang X (2017) Reference values of 14 serum trace elements for pregnant Chinese women: a cross-sectional study in china nutrition and health survey 2010-2012. Nutrients 9(3):309–318. https://doi.org/10.3390/nu9030309
Lobo V, Patil A, Phatak A, Chandra N (2010) Free radicals, antioxidants and functional foods: impact on human health. Pharm Rev 4(8):118–126. https://doi.org/10.4103/0973-7847.70902
Lowe J, Taveira-da-Silva R, Hilário-Souza E (2017) Dissection copper homeostasis in diabetes mellitus. Int Union Biochem Mol Biol 69(4):255–262. https://doi.org/10.1002/iub.1614
Nakhaee S, Amirabadizadeh A, Brent J, Mehrpour O (2019a) Impact of chronic lead exposure on liver and kidney function and haematologic parameters. Basic Clin Pharmacol Toxicol 124:621–628. https://doi.org/10.1111/bcpt.13179
Nakhaee S, Amirabadizadeh A, Zarban A, Nasirizade M, Salmani Mood M, Ataei H, Shariatmadari MR, Brent J, Mehrpour O (2019b) The reference value of blood lead level among the general adult population of eastern Iran. J Environ Sci Health A 54(13):1287–1292. https://doi.org/10.1080/10934529.2019.1640580
Noctor E, Dunne FP (2015) Type 2 diabetes after gestational diabetes: the influence of changing diagnostic criteria. World J Diabetes 6:234–244. https://doi.org/10.4239/wjd.v6.i2.234
Olechnowicz J, Tinkov A, Skalny A, Suliburska J (2017) Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Phys Ther Sci 68:19–31. https://doi.org/10.1007/s12576-017-0571-7
Pavăl D, Nemeş B, Rusu RL, Dronca E (2018) Genotype-phenotype analysis of paraoxonase 1 in schizophrenic patients treated with atypical antipsychotics. Clin Psychopharmacol Neurosci 16(1):32–38. https://doi.org/10.9758/cpn.2018.16.1.32
Pham MK, Nguyen DN, Hoang AT (2018) Influence of vanadium content on the microstructure and mechanical properties of high-manganese steel. Int J Mech Mechatron 18:141–147
Poel YH, Hummel P, Lips P, Stam F, van der Ploeg T, Simsek S (2012) Vitamin D and gestational diabetes: a systematic review and meta-analysis. European J Int Med 23:465–469. https://doi.org/10.3390/ijerph16101716
Preet A, Gupta B, Yandava PK, Baquer N (2005) Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rats lenses. J Biosci 30:221–230. https://doi.org/10.1007/bf02703702
R Core Team (2016) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.
Retnakaran R, Shah BR (2017) Role of type 2 diabetes in determining retinal, renal, and cardiovascular outcomes in women with previous gestational diabetes mellitus. Diabetes Care 40:101–108. https://doi.org/10.2337/dc16-1400
Rezaei M, Javadmoosavi SY, Mansouri B, Azadi N, Mehrpour O, Nakhaee S (2019) Thyroid dysfunction: how concentration of toxic and essential elements contribute to risk of hypothyroidism, hyperthyroidism, and thyroid cancer. Environ Sci Pollut Res 26:35787–35796. https://doi.org/10.1007/s11356-019-06632-7
Rezk NL, Rezk, SA (2017) Vanadium in therapy and toxicity: mini-review and recommendation of further study. MOJ Bioequival Bioavail 3, 105-106. 10.15406/mojbb.2017.03.00042
Robledo CA, Romano ME, Alonso-Magdalena P (2016) Review of current evidence on the impact of environmental chemicals on gestational diabetes mellitus. Current Epidemiol Reports 3:51–62. https://doi.org/10.1007/s40471-016-0070-z
Rodushkin I, Odman OF, Olofsson R, Axelsson MD (2000) Determination of 6o elements in whole blood by sector field inductively coupled plasma mass spectrometry. J Anal Ato Spectrom 15:937–944. https://doi.org/10.1039/B003561K
Roshanravan N, Alamdari NM, Ghavami A, Mousavi R, Alipour S, Ebrahimi-Mamaghani M (2018) Serum levels of copper, zinc and magnesium in pregnant women with impaired glucose tolerance test: a case-control study. Prog Nutr 20(1):325–329. https://doi.org/10.23751/pn.v20i1-S.6041
Rovira J, Hernández-Aguilera A, Luciano-Mateo F, Cabré N, Baiges-Gaya G, Nadal M, Martín-Paredero V, Camps J, Joven J, Domingo JL (2018) Trace elements and paraoxonase-1 activity in lower extremity artery disease. Biol Trace Elem Res 186:74–84. https://doi.org/10.1007/s12011-018-1298-x
Roy C, Tremblay PY, Ayotte P (2017) Is mercury exposure causing diabetes, metabolic syndrome and insulin resistance? A systematic review of the literature. Environ Res 156:747–760. https://doi.org/10.1016/j.envres.2017.04.038
Salmeri N, Villanacci R, Ottolina J, Bartiromo L, Cavoretto P, Dolci C, Lembo R, Schimberni M, Valsecchi L, Vigano P, Candini M (2020) Maternal arsenic exposure and gestational diabetes: a systematic review and meta-analysis. Nutrients 12(10):3094–4011. https://doi.org/10.3390/nu12103094
Sánchez C, Torres M, Bermúdez-Peña MC, Aranda P, Montes-Bayón M, Sanz-Medel A, Llopis J (2011) Bioavailability, tissue distribution and hypoglycaemic effect of vanadium in magnesium-deficient rats. Magnes Res 24(4):196–208. https://doi.org/10.1684/mrh.2011.0293
Shapiro GD, Dodds L, Arbuckle TE, Ashley-Martin J, Fraser W, Fisher M, Taback S, Keely E, Bouchard MF, Monnier P, Dallaire R, Morisset AS, Ettinger AS (2015) Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: the MIREC study. Environ Int 83:63–71. https://doi.org/10.1016/j.envint.2015.05.016
Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87(1):4–14. https://doi.org/10.1016/j.diabres.2009.10.007
Shen HN, Hua SY, Chiu CT, Li CY (2017) Maternal exposure to air pollutants and risk of gestational diabetes mellitus in Taiwan. Int J Environ Res Public Health 14(12):1604–1615. https://doi.org/10.3390/ijerph14121604
Sohaili K (2010) The impact of improvement in Iran iron and steel production technology on environment pollution. Procedia Environ Sci 2:262–269. https://doi.org/10.1016/j.proenv.2010.10.032
Sverdrup HU, Olafsdottir AH (2019) Assessing the long-term global sustainability of the production and supply for stainless steel. Biophys Econ Resour Qual 4:1–29. https://doi.org/10.1007/s41247-019-0056-9
Tanaka A, Kaneto H, Miyatsuka T et al (2009) Role of copper ion in the pathogenesis of type 2 diabetes. Endocr J 56(5):699–706. https://doi.org/10.1507/endocrj.K09E-051
Tinkov AA, Ajsuvakova OP, Skalnaya MG, Popova EV, Sinitskii AI, Nemereshina ON, Gatiatulina ER, Nikonorov AA, Skalny AV (2015a) Mercury and metabolic syndrome: a review of experimental and clinical observations. Biometals 28(2):231–254. https://doi.org/10.1007/s10534-015-9823-2
Tinkov AA, Sinitskii AI, Popova EV, Nemereshina ON, Gatiatulina ER, Skalnaya MG, Skalny AV, Nikonorov AA (2015b) Alteration of local adipose tissue trace element homeostasis as a possible mechanism of obesity-related insulin resistance. Med Hypotheses 85(3):343–347. https://doi.org/10.1016/j.mehy.2015.06.005
Tinkov AA, Filippini T, Ajsuvakova OP, Aaseth J, Gluhcheva YG, Ivanova JM, Bjørklund G, Skalnaya MG, Gatiatulina ER, Popova EV, Nemereshina ON, Vinceti M, Skalny AV (2017) The role of cadmium in obesity and diabetes. Sci Total Environ 601-602:741–755. https://doi.org/10.1016/j.scitotenv.2017.05.224
Treviño S, Díaz A, Sánchez-Lara E, Sanchez-Gaytan BL, Perez-Aguilar JM, González-Vergara E (2019) Vanadium in biological action: chemical, pharmacological aspects, and metabolic implications in diabetes mellitus. Biol Trace Elem Res 188:68–98. https://doi.org/10.1007/s12011-018-1540-6
Tsai TL, Huo CC, Pan WH, Wu TN, Lin P, Wang SL (2019) Type 2 diabetes occurrence and mercury exposure – from the national nutrition and health survey in Taiwan. Environ Int 126:260–267. https://doi.org/10.1016/j.envint.2019.02.038
Tseng CH (2004) The potential biological mechanism of arsenic-induced diabetes mellitus. Toxicol Appl Pharmacol 197(2):67–83. https://doi.org/10.1016/j.taap.2004.02.009
Wang X, Sun T, Liu J, Shan Z, Jin Y, Chen S, Bao W, Hu FB, Liu L (2014) Inverse association of plasma vanadium levels in newly diagnosed type 2 diabetes in a Chinese population. Am J Epidemiol 180(4):378–384. https://doi.org/10.1093/aje/kwu148
World Medical Association (2018) Declaration of Helsinki - ethical principles for medical research involving human subjects. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ Last access: 30th May 2019.
Xing Y, Xia W, Zhang B, Zhou A, Huang Z, Zhang H, Xu S (2018) Relation between cadmium exposure and gestational diabetes mellitus. Environ Int 113:300–305. https://doi.org/10.1016/j.envint.2018.01.001
Yogev Y, Catalano PM (2009) Pregnancy and obesity. Obstet Gynecol Clin N Am 36(2):285–300. https://doi.org/10.1016/j.ogc.2009.03.003
Zardast M, Khorashadi-Zadeh SS, Nakhaee S, Amirabadizadeh A, Mehrpour O (2020) Blood lead concentration and its associated factors in preschool children in eastern Iran: a cross-sectional study. BMC Pediatr 20:435. https://doi.org/10.1186/s12887-020-02302-7
Zheng T, Liu S, Bai Y et al (2018) Current understanding of the relationship between metal exposures and risk of type 2 diabetes. Curr Res Diabetes Obes J 7(2). https://doi.org/10.19080/CRDOJ.2018.07.555710
American Diabetes Association (2014) Diagnosis and classification of Diabetes Mellitus. Diabetes Care 37(1):81–90. https://doi.org/10.2337/dc14-S081
Dantione TF, Debord J, Merle L, Lacroix-Ramiandrisoa H, Bourzeix L, Charmes JP (2002) Paranoxase 1 activity: a new vascular marker of dementia? Ann. N Y Acad Sci. 977:96–101. https://doi.org/10.1111/j.1749-6632.2002.tb04802.x
Acknowledgement
The authors would like to acknowledge the Medical Toxicology and Drug Abuse Research Center at Birjand University of Medical Sciences for their assistance. We thank R. Rajaei, H. Ataei, and A. Amirabadizadeh for their contribution. We are also very grateful to all of the patients who participated in this project.
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This project was generously supported financially by Birjand University of Medical Sciences (Grant No. 1398/5231).
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MR, MB, AAT, LJB, BM, AS, MDD, and GB contributed to the design of the study, the interpretation of the results, and the drafting of the manuscript. MR and BM conducted the collection of the data. NA and LJB conducted the statistical analyses. All authors have read and approved the final version of the manuscript.
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This study was conducted in accordance with the World Medical Association Declaration of Helsinki (WMA, 2018). This study was approved by the research and ethics committee of Birjand University of Medical Sciences (IR.BUMS.REC.1398.398).
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Highlights
• Levels of As, Cd and Hg were significantly higher in women with GDM.
• Multivariate analyses clearly classify subjects with GDM based on metal levels.
• Elevated As, Cd and Hg levels increased the possibility of the development of GDM, while elevated V level lower that risk.
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Rezaei, M., Błaszczyk, M., Tinkov, A.A. et al. Relationship between gestational diabetes and serum trace element levels in pregnant women from Eastern Iran: a multivariate approach. Environ Sci Pollut Res 28, 45230–45239 (2021). https://doi.org/10.1007/s11356-021-13927-1
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DOI: https://doi.org/10.1007/s11356-021-13927-1