Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, is defined as glucose intolerance with onset or first recognition during pregnancy. Its prevalence varies worldwide in dependence on characteristics of the underlying population and applied diagnostic criteria. The etiology is multifactorial and not sufficiently elucidated. Available evidence suggests that the base of pathogenesis is relatively diminished insulin secretion coupled with pregnancy-induced insulin resistance. Modifiable and non-modifiable risk factors for development have been identified. Trace elements and vitamin D could be contributed to modifiable factors for prediction the risk in a large population. Essential trace elements in pregnancy are necessary to overcome systemic oxidative, metabolic and inflammatory stress. Evidence, still inconclusive, has been accumulated about the relation between higher incidence of vitamin D failure/deficiency during pregnancy and GDM. The lower level of 25-OH vitamin D could be associated with increased risk for anemia development, also including pregnant women. This review intends to provide an overview of the possible link between both vitamin D and trace elements as risk factors for GDM development.
1. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy (WHO/NMH/ MND/13.2). Geneva: World Health Organization; 2013.
2. Beckmann CRB, Ling F, Herbert WNP et al. Obstetrics and Gynecology. 7th ed. Baltimore; Lippincott Williams and Wilkins, 2014.
3. Bowers K, Yeung E, Williams MA et al. A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus. Diabetes Care 2011;34 (7):1557-63.
4. Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta 2012, 1823(9):1434-1443.
5. Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr 2006;26: 323-42.
6. Fernández-Real JM, McClain D, Manco M. Mechanisms Linking Glucose Homeostasis and Iron Metabolism Toward the Onset and Progression of Type 2 Diabetes. Diabetes Care 2015;38 (11):2169-76.
7. Wang H., Li H., X. Jianq X et al. Hepcidin is directly regulated by insulin and plays an important role in iron overload in streptozotocin- induced diabetic rats. Diabetes 2014;63(5):1506-18.
8. Puntarolo S. Iron, oxidative stress and human health. Mol Aspcts Med 2005;26(4-5):299-312.
9. Fernández-Real JM, Lopez-Bermejo A, Ricart W. Crosstalk between iron metabolism and diabetes. Diabetes 2002;51(8):2348-54.
10. Khambalia AZ., Collins CE, Roberts CL et al. Iron deficiency in early pregnancy using serum ferritin and soluble transferrin receptor concentrations are associated with pregnancy and birth outcomes. Eur J Clin Nutr 2016;70(3):358-63.
11. SharifiF, Ziaee A, Feizi A et al. Serum ferritin concentration in gestational diabetes mellitus and risk of subsequent development of early postpartum diabetes mellitus. Diabetes Metab Syndr Obes 2010;3:413-9.
12. Behboudi-Gandevani S, Safary K, Moghaddam-Banaem L et al. The relationship between maternal serum iron and zinc levels and their nutritional intakes in early pregnancy with gestational diabetes. Biol. Trace Elem Res 2013: 154(1):7-13.
13. Li X, Lu X. Study on correlation between C-reactive protein and gestational diabetes mellitus. JNMU 2007;21:382-85.
14. Harms K, Kaise T. Beyond soluble transferrin receptor: old challenges and new horizons. Best Pract Res Clin Endocrinol Metab 2015;29(5):799-810.
15. Koenig MD, L. Tussing-Humphreys L, Day J et al. Hepcidinand iron homeostasis during pregnancy. Nutrients 2014;6(8):3062-83.
16. Petkova-Marinova T, Ruseva B. Relationship of hepcidin levelsto parameters of iron metabolism during pregnancy. Archives of the Balkan Medical Union 2015; 1-16.
17. Freeland-Graves JH, Sanjeevi N, Lee JJ. Global perspectives on trace element requirements. J Trace Elem Med Biol 2015;31:135-41.
18. Spencer BH., Vanderlelie JJ, Perkins AV. Essentiality of Trace Element Micronutrition in Human Pregnancy: A systematic review. J Preg Child Health 2015;2:157 doi:
19. McArdle HJ, Andersen HS, Jones H, gambling L. Copper and iron transport across the placenta: regulation and interactions. J Neuroendocrinol 2008;20(4):427-31.
20. Alvarez SI., Castanon SG, Ruata ML et al. Updating of normal levels of copper, zinc and selenium in serum of pregnant women. J Trace Elem Med Biol 2007;21 (Suppl):49-52.
21. Louro M.O., J.A. Cocho and J.C. Tutor. Assessment of copper status in pregnancy by means of determining the specific oxidase activity of ceruloplasmin. Clin Chim Acta 2001;312(1- 2): 123-7.
22. Braga F, Szoke, Valente C, Panteghini M. Biologic variation of copper, ceruloplasmin and copper/ceruloplasmin ratio (Cu:Cp) in serum. Clin Chim Acta 2013;415:295-6.
23. Asha D, Nivedita N, Daniel M et al. Association of serum copper level with fasting serum glucose in south Indian women with gestational diabetes mellitus. Int J Clin Exp Physiol 2014;1:298-302.
24. Gambling L, Andersen H, McArdle HJ. Iron and copper, and their interactions during development. Biochem Soc Trans 2008; 36(Pt 6):1258-61.
25. Rungby J. Zinc, zinc transporters and diabetes. Diabetologia 2010;53(8):1549-51.
26. Jansen J, Karges W, Rink L. Zinc and diabetes - clinical links and molecular mechanisms. J Nutr Biochem 2009;20(6):399-417.
27. ButlerWalker J, Houseman J, Seddon L et al. Maternal and umbilical cord blood levels of mercury, lead, cadmium, and essential trace elements in Arctic Canada. Environ Res 2006; 100 (3):295-318.
28. WHO/FAO/IAEA, Trace Elements in Human Nutrition and Health, World Health Organisation, Geneva, Switzerland, 1996.
29. Rayman MP. The importance of selenium to human healt. Lancet 2000;356(9225):233-41.
30. Stapleton SR. Selenium: an insulin-mimetic. Cell Mol Life Sci 2000;57(13-14):1874-9.
31. Shibata M, Suzuki A, Sekiya T et al. High prevalence of hypovitaminosis D in pregnant Japanese women with threatened premature delivery. J Bone Miner Metab 2011;29(5):615-20.
32. Chagas CE, Borges MC, Martini LA, Rogero MM. Focus on vitamin D, inflammation and type 2 diabetes. Nutrients 2012;4(1):52-67.
33. Asemi Z, Samimi M, Tabassi Z et al. Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women. J Nutr 2013;143:1432-38.
34. Evans KN, Bulmer JN, Kilby MD, Hewison M. Vitamin D and placental-decidual function. J Soc Gynecol Investig 2004;11(5):263-71.
35. Zhang MX, Pan GT, Guo GF et al. Vitamin D Deficiency Increases the Risk of Gestational Diabetes Mellitus: A Meta-Analysis of Observational Studies. Nutrients 2015;7(10):8366-75.
36. Bener A, A. Al-Hamaq AA, Saleh NM. Association between vitamin D insufficiency and adverse pregnancy outcome: global comparisons. Int J Womens Health 2013;5:523-31.
37. Lu M, Xu Y, Lv L, Zhang M. Association between vitamin D status and the risk of gestational diabetes mellitus: a metaanalysis. Arch Gynecol Obstet 2016;293(5):959-66.
38. Flood-Nichols SK, Tinnemore D, Huang RR et al. Vitamin D deficiency in early pregnancy - PLoS One 2015; e0123763.
39. Bacchetta J, Zaritsky J, Sea JL et al. Suppression of ironregulatory hepcidin by vitamin D. J Am Soc Nephrol 2014; 25(3):564-72.
40. Watson R. Handbook of Vitamin D in Human Health: prevention, treatment and toxicity. The Netherlands, Wageningen Academic Publishers; 2013.