Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Increased cord blood angiotensin II concentration is associated with decreased insulin sensitivity in the offspring of mothers with gestational diabetes mellitus

Journal of Perinatology volume 33, pages 9–14 (2013)Cite this article

Subjects

Abstract

Objective:

To determine cord blood angiotensin II (Ang II) concentration and assess its relationship to fetal insulin sensitivity in the offspring of mothers with gestational diabetes mellitus (GDM) at birth.

Study Design:

Thirty women with GDM and 30 healthy women were evaluated at elective cesarean delivery. Cord blood was obtained for measurement of Ang II, glucose and insulin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated and used to estimate fetal insulin sensitivity.

Result:

The offspring of mothers with GDM had higher ponderal index (PI), HOMA-IR and cord Ang II and insulin concentrations than the offspring of healthy mothers. Cord insulin concentration and HOMA-IR were positively associated with PI in all the offspring. Cord Ang II concentration was positively associated with HOMA-IR in the offspring of mothers with GDM.

Conclusion:

Increased cord Ang II concentration is associated with decreased insulin sensitivity in the offspring of mothers with GDM.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Expert committee on the diagnosis and classification of diabetes mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–1197.

  2. Boney CM, Verma A, Tucker R, Vohr BR . Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005; 115: 290–296.

    Article  Google Scholar 

  3. Clausen TD, Mathiesen ER, Hansen T, Pedersen O, Jensen DM, Lauenborg J et al. Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes. J Clin Endocrinol Metab 2009; 94: 2464–2470.

    Article  CAS  Google Scholar 

  4. Ma RC, Chan JC . Pregnancy and diabetes scenario around the world: China. Int J Gynaecol Obstet 2009; 104 (Suppl 1): S42–S45.

    Article  Google Scholar 

  5. de Gusmão Correia ML, Volpato AM, Aguila MB, Mandarim-de-Lacerda CA . Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome. J Hum Hypertens 2011; e-pub ahead of print 23 Jun 2011; doi:10.1038/jhh.2011.61.

  6. Luo ZC, Delvin E, Fraser WD, Audibert F, Deal CI, Julien P et al. Maternal glucose tolerance in pregnancy affects fetal insulin sensitivity. Diabetes Care 2010; 33: 2055–2061.

    Article  CAS  Google Scholar 

  7. Alkheenizan AH, Alswes MA . The role of renin blockers in the prevention of diabetes. Saudi Med J 2007; 28: 91–95.

    Google Scholar 

  8. de Kloet AD, Krause EG, Woods SC . The renin angiotensin system and the metabolic syndrome. Physiol Behav 2010; 100: 525–534.

    Article  CAS  Google Scholar 

  9. Olivares-Reyes JA, Arellano-Plancarte A, Castillo-Hernandez JR . Angiotensin II and the development of insulin resistance: implications for diabetes. Mol Cell Endocrinol 2009; 302: 128–139.

    Article  CAS  Google Scholar 

  10. Taguchi K, Kobayashi T, Takenouchi Y, Matsumoto T, Kamata K . Angiotensin II causes endothelial dysfunction via the GRK2/Akt/eNOS pathway in aortas from a murine type 2 diabetic model. Pharmacol Res 2011; 64: 535–546.

    Article  CAS  Google Scholar 

  11. van der Zijl NJ, Moors CC, Goossens GH, Hermans MM, Blaak EE, Diamant M . Valsartan improves {beta}-cell function and insulin sensitivity in subjects with impaired glucose metabolism: a randomized controlled trial. Diabetes Care 2011; 34: 845–851.

    Article  CAS  Google Scholar 

  12. Saiki A, Ohira M, Endo K, Koide N, Oyama T, Murano T et al. Circulating angiotensin II is associated with body fat accumulation and insulin resistance in obese subjects with type 2 diabetes mellitus. Metabolism 2009; 58: 708–713.

    Article  CAS  Google Scholar 

  13. van Dijk DJ, Boner G, Giler S, Erman A . Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat. J Renin Angiotensin Aldosterone Syst 2001; 2: 193–198.

    Article  CAS  Google Scholar 

  14. Zhang XL . Diabetes. In: Le J (ed). Obstetrics and Gynecology. People's Medical Publishing House: Beijing, 2004, pp 160.

    Google Scholar 

  15. Broughton Pipkin F, Symonds EM . Factors affecting angiotensin II concentrations in the human infant at birth. Clin Sci Mol Med 1977; 52: 449–456.

    CAS  PubMed  Google Scholar 

  16. Basu S, Laffineuse L, Presley L, Minium J, Catalano PM, Hauguel-de Mouzon S . In utero gender dimorphism of adiponectin reflects insulin sensitivity and adiposity of the fetus. Obesity (Silver Spring) 2009; 17: 1144–1149.

    CAS  Google Scholar 

  17. Catalano PM, Presley L, Minium J, Hauguel-de Mouzon S . Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care 2009; 32: 1076–1080.

    Article  CAS  Google Scholar 

  18. Pedersen J . The Pregnant Diabetic and Her Newborn: Problems and Management. Williams & Wilkins: Baltimore, 1967, pp 60–107.

    Google Scholar 

  19. Westgate JA, Lindsay RS, Beattie J, Pattison NS, Gamble G, Mildenhall LF et al. Hyperinsulinemia in cord blood in mothers with type 2 diabetes and gestational diabetes mellitus in New Zealand. Diabetes Care 2006; 29: 134513–134550.

    Article  Google Scholar 

  20. Shiuchi T, Iwai M, Li HS, Wu L, Min LJ, Li JM et al. Angiotensin II type-1 receptor blocker valsartan enhances insulin sensitivity in skeletal muscles of diabetic mice. Hypertension 2004; 43: 1003–1010.

    Article  CAS  Google Scholar 

  21. Hanyu O, Miida T, Obayashi K, Ikarashi T, Soda S, Kaneko S et al. Lipoprotein lipase (LPL) mass in preheparin serum reflects insulin sensitivity. Atherosclerosis 2004; 174: 385–390.

    Article  CAS  Google Scholar 

  22. Batlle D, Jose Soler M, Ye M . ACE2 and diabetes: ACE of ACEs? Diabetes 2010; 59: 2994–2996.

    Article  CAS  Google Scholar 

  23. Wei Y, Sowers JR, Nistala R, Gong H, Uptergrove GM, Clark SE et al. Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells. J Biol Chem 2006; 281: 35137–35146.

    Article  CAS  Google Scholar 

  24. Kobayashi T, Nogami T, Taguchi K, Matsumoto T, Kamata K . Diabetic state, high plasma insulin and angiotensin II combine to augment endothelin-1-induced vasoconstriction via ETA receptors and ERK. Br J Pharmacol 2008; 155: 974–983.

    Article  CAS  Google Scholar 

  25. Bian YF, Yang HY, Yang ZM, Gao F, Zhang NN, Xiao CS . Amlodipine treatment prevents angiotensin II-induced human umbilical vein endothelial cell apoptosis. Arch Med Res 2011; 42: 22–27.

    Article  CAS  Google Scholar 

  26. Tuck ML, Bounoua F, Eslami P, Nyby MD, Eggena P, Corry DB . Insulin stimulates endogenous angiotensin II production via a mitogen-activated protein kinase pathway in vascular smooth muscle cells. J Hypertens 2004; 22: 1779–1785.

    Article  CAS  Google Scholar 

  27. Samuelsson AM, Bollano E, Mobini R, Larsson BM, Omerovic E, Fu M et al. Hyperinsulinemia: effect on cardiac mass/function, angiotensin II receptor expression, and insulin signaling pathways. Am J Physiol Heart Circ Physiol 2006; 291: H787–H796.

    Article  CAS  Google Scholar 

  28. Saiki A, Ohira M, Endo K, Koide N, Oyama T, Murano T et al. Pioglitazone decreases plasma angiotensin II concentration in type 2 diabetes. J Atheroscler Thromb 2010; 17: 651–657.

    Article  CAS  Google Scholar 

  29. Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM . Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors. Diabetes 2002; 51: 1699–1707.

    Article  CAS  Google Scholar 

  30. Saiki A, Koide N, Watanabe F, Murano T, Miyashita Y, Shirai K . Suppression of lipoprotein lipase expression in 3T3-L1 cells by inhibition of adipogenic differentiation through activation of the renin-angiotensin system. Metabolism 2008; 57: 1093–1100.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by Chongqing Municipality Education Commission (2010-KJ100312).

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    F Zhang & X Zhang

  2. Insitute of Life Sciences, Chongqing Medical University, Chongqing, China

    X Xiao

  3. Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    D Liu

  4. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    X Dong & J Sun

Authors
  1. F Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X Zhang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, F., Xiao, X., Liu, D. et al. Increased cord blood angiotensin II concentration is associated with decreased insulin sensitivity in the offspring of mothers with gestational diabetes mellitus. J Perinatol 33, 9–14 (2013). https://doi.org/10.1038/jp.2012.40

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2012.40

Keywords

This article is cited by

Search

Advanced search

Quick links