, Volume 16, Issue 3, pp 282–290 | Cite as

Maternal serum placental growth hormone, insulin-like growth factors and their binding proteins at 20 weeks’ gestation in pregnancies complicated by gestational diabetes mellitus

  • Shutan Liao
  • Mark H. Vickers
  • Rennae S. Taylor
  • Mhoyra Fraser
  • Lesley M. E. McCowan
  • Philip N. Baker
  • Jo K. PerryEmail author
Research paper



To investigate whether maternal serum concentrations of placental growth hormone (GH-V), insulin-like growth factor (IGF) 1 and 2, and IGF binding proteins (IGFBP) 1 and 3 were altered in pregnancies complicated by gestational diabetes mellitus (GDM).


In a nested case-control study, GDM cases (n=28) and matched controls (n=28) were selected from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Maternal serum hormone concentrations at 20 weeks of gestation were determined by enzyme-linked immunosorbent assay (ELISA).


There was no significant difference in maternal serum GH-V concentration in the GDM group compared to the control group (1.64 ± 0.11 ng/ml vs. 1.38 ± 0.10 ng/ml, p=0.079). However, GDM cases who delivered large for gestational age (LGA) babies had significantly higher serum GH-V concentrations compared to non-diabetic control cases. Maternal IGF-1 concentrations in GDM pregnancies were significantly higher than in controls (275.7 ± 11.5 ng/ml vs. 218.5 ± 11.1 ng/ml, p <0.001). Maternal IGFBP-1 concentrations were significantly lower in GDM pregnancies than in controls (41.04 ± 3.42 ng/ml vs. 67.58 ± 6.17 ng/ml, p <0.001). There were no significant differences in serum IGF-2 and IGFBP-3 concentrations between groups.


Concentrations of IGF-1 and IGFBP-1 in maternal serum were altered in GDM pregnancies compared to controls, suggesting that the IGF axis plays a role in the development of this condition. GH-V may be associated with macrosomia as increased maternal GH-V was observed in GDM cases who delivered LGA babies.

Key words

Binding proteins Gestational diabetes mellitus Insulin-like growth factor Placental growth hormone Pregnancy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Colagiuri S, Falavigna M, Agarwal MM, et al, 2014 Strategies for implementing the WHO diagnostic criteria and classification of hyperglycaemia first detected in pregnancy. Diabetes Res Clin Pract 103: 364–372.CrossRefPubMedGoogle Scholar
  2. 2.
    Zhu Y, Zhang C, 2016 Prevalence of Gestational Diabetes and Risk of Progression to Type 2 Diabetes: a Global Perspective. Curr Diab Rep 16: 7.CrossRefPubMedGoogle Scholar
  3. 3.
    Langer O, Yogev Y, Most OXenakis EM, 2005 Gestational diabetes: the consequences of not treating. Am J Obstet Gynecol 192: 989–997.CrossRefPubMedGoogle Scholar
  4. 4.
    Catalano PM, Kirwan JP, Haugel-de Mouzon SKing J, 2003 Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus. J Nutr 133: 5 Suppl 2: 1674–1683.CrossRefGoogle Scholar
  5. 5.
    Hirt H, Kimelman J, Birnbaum MJ, et al, 1987 The human growth hormone gene locus: structure, evolution, and allelic variations. DNA 6: 59–70.CrossRefPubMedGoogle Scholar
  6. 6.
    Alsat E, Guibourdenche J, Luton D, Frankenne FEvain-Brion D. 1997 Human placental growth hormone. Am J Obstet Gynecol 177: 1526–1534.CrossRefPubMedGoogle Scholar
  7. 7.
    Alsat E, Guibourdenche J, Couturier AE, vain-Brion D. 1998 Physiological role of human placental growth hormone. Mol Cell Endocrinol 140: 121–127.CrossRefPubMedGoogle Scholar
  8. 8.
    Eriksson L, Frankenne F, Eden S, Hennen G, Von Schoultz B, 1989 Growth hormone 24-h serum profiles during pregnancy—lack of pulsatility for the secretion of the placental variant. Br J Obstet Gynaecol 96: 949–953.CrossRefPubMedGoogle Scholar
  9. 9.
    Newbern D, Freemark M, 2011 Placental hormones and the control of maternal metabolism and fetal growth. Curr Opin Endocrinol Diabetes Obes 18: 409–416.CrossRefPubMedGoogle Scholar
  10. 10.
    Barbour LA, Shao J, Qiao L, et al, 2002 Human placental growth hormone causes severe insulin resistance in transgenic mice. Am J Obstet Gynecol 186: 512–517.CrossRefPubMedGoogle Scholar
  11. 11.
    Liao S, Vickers MH, Stanley JL, et al, 2016 The Placental Variant of Human Growth Hormone Reduces Maternal Insulin Sensitivity in a Dose-Dependent Manner in C57BL/6J Mice. Endocrinology 157: 1175–1186.CrossRefPubMedGoogle Scholar
  12. 12.
    Liao S, Vickers MH, Evans A, et al, 2016 Comparison of pulsatile vs. continuous administration of human placental growth hormone in female C57BL/6J mice. Endocrine: 1–13.Google Scholar
  13. 13.
    Chellakooty M, Vangsgaard K, Larsen T, et al, 2004 A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth. J Clin Endocrinol Metab 89: 384–391.CrossRefPubMedGoogle Scholar
  14. 14.
    McIntyre HD, Serek R, Crane DI, et al, 2000 Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth. J Clin Endocrinol Metab 85: 1143–1150.PubMedGoogle Scholar
  15. 15.
    Pedersen NG, Juul A, Christiansen M, Wojdemann KRTabor A, 2010 Maternal serum placental growth hormone, but not human placental lactogen or insulin growth factor-1, is positively associated with fetal growth in the first half of pregnancy. Ultrasound Obst Gyn 36: 534–541.CrossRefGoogle Scholar
  16. 16.
    Liao S, Vickers MH, Taylor RS, et al, 2016 Human placental growth hormone is increased in maternal serum at 20 weeks of gestation in pregnancies with large-for-gestational-age babies. Growth Factors 34: 203–209.CrossRefPubMedGoogle Scholar
  17. 17.
    Caufriez A, Frankenne F, Hennen G, Copinschi G. 1993 Regulation of maternal IGF-I by placental GH in normal and abnormal human pregnancies. Am J Physiol 265: E572–577.PubMedGoogle Scholar
  18. 18.
    Caufriez A, Frankenne F, Hennen G, Copinschi G, 1994 Regulation of maternal insulin-like growth factor I by placental growth hormone in pregnancy. Possible action of maternal IGF-I on fetal growth. Horm Res 42: 62–65.CrossRefPubMedGoogle Scholar
  19. 19.
    Caufriez A, Frankenne F, Englert Y, et al, 1990 Placental growth hormone as a potential regulator of maternal IGF-I during human pregnancy. Am J Physiol 258: E1014–E1019.PubMedGoogle Scholar
  20. 20.
    Forbes K, Westwood M, 2008 The IGF axis and placental function, a mini review. Horm Res 69: 129–137.PubMedGoogle Scholar
  21. 21.
    Chard T, 1994 Insulin-like growth factors and their binding proteins in normal and abnormal human fetal growth. Growth Regul 4: 91–100.PubMedGoogle Scholar
  22. 22.
    Holt RI, Simpson HL, Sonksen PH, 2003 The role of the growth hormone-insulin-like growth factor axis in glucose homeostasis. Diabet Med 20: 3–15.CrossRefPubMedGoogle Scholar
  23. 23.
    Fuglsang J, Lauszus F, Flyvbjerg A, Ovesen P, 2003 Human placental growth hormone, insulin-like growth factor I and -II, and insulin requirements during pregnancy in type 1 diabetes. J Clin Endocrinol Metab 88: 4355–4361.CrossRefPubMedGoogle Scholar
  24. 24.
    Matuszek B, Lenart-Lipinska M, Burska A, et al, 2011 Increased serum insulin-like growth factor-1 levels in women with gestational diabetes. Adv Med Sci 56: 200–206.CrossRefPubMedGoogle Scholar
  25. 25.
    Yan-Jun L, Tsushima T, Minei S, et al, 1996 Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBP-1, -2 and -3) in diabetic pregnancy: relationship to macrosomia. Endocrine Journal 43: 221–231.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhu Y, Mendola P, Albert PS, et al, 2016 Insulin-like growth factor axis and gestational diabetes: A longitudinal study in a multiracial cohort. Diabetes.Google Scholar
  27. 27.
    McCowan L, North RTaylor R. (2007).Google Scholar
  28. 28.
    Simmons D, Rowan J, Reid R, Campbell N, 2008 Screening, diagnosis and services for women with gestational diabetes mellitus (GDM) in New Zealand: a technical report from the National GDM Technical Working Party. N Z Med J 121: 74–86.PubMedGoogle Scholar
  29. 29.
    Solomon G, Reicher S, Gussakovsky EE, Jomain JB, Gertler A, 2006 Large-scale preparation and in vitro characterization of biologically active human placental (20 and 22K) and pituitary (20K) growth hormones: placental growth hormones have no lactogenic activity in humans. Growth Horm IGF Res 16: 297–307.CrossRefPubMedGoogle Scholar
  30. 30.
    Liao S, Vickers MH, Taylor RS, et al, Human placental growth hormone is increased in maternal serum at 20 weeks of gestation in pregnancies with large-for-gestational-age babies. Growth Factors 2016 Dec;34(5–6):203–209. doi: Scholar
  31. 31.
    Patel N, Alsat E, Igout A, et al, 1995 Glucose inhibits human placental GH secretion, in vitro. J Clin Endocrinol Metab 80: 1743–1746.PubMedGoogle Scholar
  32. 32.
    Bjorklund AO, Adamson UK, Carlstrom KA, et al, 1998 Placental hormones during induced hypoglycaemia in pregnant women with insulin-dependent diabetes mellitus: evidence of an active role for placenta in hormonal counter-regulation. Br J Obstet Gynaecol 105: 649–655.CrossRefPubMedGoogle Scholar
  33. 33.
    Higgins MF, Russell NE, Crossey PA, et al, 2012 Maternal and fetal placental growth hormone and IGF axis in type 1 diabetic pregnancy. PLoS One 7: e29164.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Verhaeghe J, Pintiaux A, Van Herck E, et al, 2002 Placental GH, IGF-I, IGF-binding protein-1, and leptin during a glucose challenge test in pregnant women: relation with maternal body weight, glucose tolerance, and birth weight. J Clin Endocrinol Metab 87: 2875–2882.CrossRefPubMedGoogle Scholar
  35. 35.
    Fuglsang J, Lauszus FF, Fisker S, Flyvbjerg A, Ovesen P, 2005 Growth hormone binding protein and maternal body mass index in relation to placental growth hormone and insulin requirements during pregnancy in type 1 diabetic women. Growth Horm IGF Res 15: 223–230.CrossRefPubMedGoogle Scholar
  36. 36.
    Clemmons DR, 2004 The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J Clin Invest 113: 25–27.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Baxter RC, 1994 Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res 42: 140–144.CrossRefPubMedGoogle Scholar
  38. 38.
    Wheatcroft SB, Kearney MT, 2009 IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis. Trends Endocrinol Metab 20: 153–162.CrossRefPubMedGoogle Scholar
  39. 39.
    Collett-Solberg PF, Cohen P, 1996 The role of the insulin-like growth factor binding proteins and the IGFBP proteases in modulating IGF action. Endocrinol Metab Clin North Am 25: 591–614.CrossRefPubMedGoogle Scholar
  40. 40.
    Kim HS, 2013 Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism. Ann Pediatr Endocrinol Metab 18: 9–12.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kim HS, Ali O, Shim M, et al, 2007 Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo. Pediatr Res 61: 159–164.CrossRefPubMedGoogle Scholar
  42. 42.
    Yamada PM, Mehta HH, Hwang D, et al, 2010 Evidence of a role for insulin-like growth factor binding protein (IGFBP)-3 in metabolic regulation. Endocrinology 151: 5741–5750.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Mohanraj L, Kim HS, Li W, et al, 2013 IGFBP-3 inhibits cytokine-induced insulin resistance and early manifestations of atherosclerosis. PLoS One 8: e55084.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Lee PD, Giudice LC, Conover CA, Powell DR, 1997 Insulin-like growth factor binding protein-1: recent findings and new directions. Proc Soc Exp Biol Med 216: 319–357.CrossRefPubMedGoogle Scholar
  45. 45.
    Lewitt MS, Denyer GS, Cooney GJ, Baxter RC, 1991 Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology 129: 2254–2256.CrossRefPubMedGoogle Scholar
  46. 46.
    Katz LE, DeLeon DD, Zhao H, Jawad AF, 2002 Free and total insulin-like growth factor (IGF)-I levels decline during fasting: relationships with insulin and IGF-binding protein-1. J Clin Endocrinol Metab 87: 2978–2983.CrossRefPubMedGoogle Scholar
  47. 47.
    Rajkumar K, Krsek M, Dheen ST, Murphy LJ, 1996 Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice. J Clin Invest 98: 1818–1825.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Buyalos RP, Pekonen F, Halme JK, Judd HL, Rutanen EM, 1995 The relationship between circulating androgens, obesity, and hyperinsulinemia on serum insulin-like growth factor binding protein-1 in the polycystic ovarian syndrome. Am J Obstet Gynecol 172: 932–939.CrossRefPubMedGoogle Scholar
  49. 49.
    Mogul HR, Marshall M, Frey M, et al, 1996 Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women. J Clin Endocrinol Metab 81: 4492–4495.PubMedGoogle Scholar
  50. 50.
    Luo ZC, Nuyt AM, Delvin E, et al, 2012 Maternal and fetal IGF-I and IGF-II levels, fetal growth, and gestational diabetes. J Clin Endocrinol Metab 97: 1720–1728.CrossRefPubMedGoogle Scholar
  51. 51.
    Ramirez VI, Miller E, Meireles CL, et al, 2014 Adiponectin and IGFBP-1 in the development of gestational diabetes in obese mothers. BMJ Open Diabetes Res Care 2: e000010.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Hughes SC, Johnson MR, Heinrich GHolly JM, 1995 Could abnormalities in insulin-like growth factors and their binding proteins during pregnancy result in gestational diabetes? J Endocrinol 147: 517–524.CrossRefPubMedGoogle Scholar
  53. 53.
    Qiu C, Vadachkoria S, Meryman L, Frederick IO, Williams MA, 2005 Maternal plasma concentrations of IGF-1, IGFBP-1, and C-peptide in early pregnancy and subsequent risk of gestational diabetes mellitus. Am J Obstet Gynecol 193: 1691–1697.CrossRefPubMedGoogle Scholar
  54. 54.
    Verhaeghe J, 2008 Does the physiological acromegaly of pregnancy benefit the fetus? Gynecol Obstet Invest 66: 217–226.CrossRefPubMedGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2017

Authors and Affiliations

  • Shutan Liao
    • 1
    • 2
    • 5
  • Mark H. Vickers
    • 1
    • 2
  • Rennae S. Taylor
    • 3
  • Mhoyra Fraser
    • 4
  • Lesley M. E. McCowan
    • 3
  • Philip N. Baker
    • 1
    • 2
    • 6
  • Jo K. Perry
    • 1
    • 2
    Email author
  1. 1.The Liggins InstituteUniversity of AucklandAucklandNew Zealand
  2. 2.Gravida: National Centre for Growth and DevelopmentAucklandNew Zealand
  3. 3.Department of Obstetrics and GynaecologyUniversity of AucklandAucklandNew Zealand
  4. 4.Department of PhysiologyUniversity of AucklandAucklandNew Zealand
  5. 5.The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  6. 6.College of Medicine, Biological Sciences and PsychologyUniversity of LeicesterLeicesterUK

Personalised recommendations