Skip to main content
SpringerLink
Log in

Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

As shown in the previous studies, asymmetric dimethylarginine (ADMA) is related to endothelial dysfunction, whereas high-sensitive C-reactive protein (hCRP) is the marker of inflammation. In our study, we investigated ADMA, hCRP, and homocysteine concentrations in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) during late pregnancy. Fifty-four women with GDM and 69 women with NGT between 32 and 39 weeks of gestation were included in this study. ADMA, hCRP, homocysteine, lipid parameters, glycated hemoglobin (HbA1c) levels, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. The plasma ADMA concentrations were significantly higher in GDM patients than in NGT subjects (P = 0.03) and the hCRP levels were also significantly increased in GDM group when compared with those in the NGT group (P = 0.008). However, plasma homocysteine levels did not differ between the groups (P = 0.4), while HOMA-IR, insulin, and triglyceride levels were higher in the GDM group than in the NGT group (P = 0.001, 0.002, and 0.02, respectively). The ADMA concentrations in the third trimester were positively correlated with the glucose levels the 50-g glucose challenge test (GCT) during 24–28 weeks in the whole group (r = 0.21, P = 0.02). Our results demonstrate that ADMA and hCRP are elevated in women with GDM during late pregnancy. Further studies are needed to clarify the significance and the underlying mechanisms of the elevated ADMA and hCRP levels in women with GDM.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. B.E. Metzger, T.A. Buchanan, D.R. Coustan, A. de Leiva, D.B. Dunger, D.R. Hadden, M. Hod, J.L. Kitzmiller, S.L. Kjos, J.N. Oats, D.J. Pettitt, D.A. Sacks, C. Zoupas, Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 30, 251–260 (2007)

    Article  Google Scholar 

  2. B.E. Metzger, D.R. Coustan, Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care 21, 161–167 (1998)

    Google Scholar 

  3. E. Anastasiou, J.P. Lekakis, M. Alevizaki, C.M. Papamichael, J. Megas, A. Souvatzoglou, S.F. Stamatelopoulos, Impaired endothelium dependent vasodilatation in women with previous gestational diabetes. Diabetes Care 21, 2111–2115 (1998)

    Article  CAS  PubMed  Google Scholar 

  4. M.M. Hannemann, W.G. Liddell, A.C. Shore, P.M. Clark, J.E. Tooke, Vascular function in women with previous gestational diabetes mellitus. J. Vasc. Res. 39, 311–319 (2002)

    Article  PubMed  Google Scholar 

  5. S. Bo, S. Valpreda, G. Menato, C. Bardelli, C. Botto, R. Gambino, C. Rabbia, M. Durazzo, M. Cassader, M. Massobrio, G. Pagano, Should we consider gestational diabetes a vascular risk factor? Atherosclerosis 194, 72–79 (2007)

    Article  Google Scholar 

  6. G. Di Cianni, C. Lencioni, L. Volpe, A. Ghio, I. Cuccuru, G. Pellegrini, L. Benzi, R. Miccoli, S. Del Prato, C-reactive protein and metabolic syndrome in women with previous gestational diabetes. Diabetes Metab. Res. Rev. 23, 135–140 (2007)

    Article  CAS  PubMed  Google Scholar 

  7. V. Mallika, B. Goswami, M. Rajappa, Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology 58, 513–522 (2007)

    Article  CAS  PubMed  Google Scholar 

  8. R.H. Böger, Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the “L-arginine paradox” and acts as a novel cardiovascular risk factor. J. Nutr. 134, 2842–2847 (2004)

    Google Scholar 

  9. P. Vallance, A. Leone, A. Calver, J. Collier, S. Moncada, Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339, 572–575 (1992)

    Article  CAS  PubMed  Google Scholar 

  10. R. Siekmeier, T. Grammer, W. März, Roles of oxidants, nitric oxide, and asymmetric dimethylarginine in endothelial function. J. Cardiovasc. Pharmacol. Ther. 13, 279–297 (2008)

    Article  CAS  PubMed  Google Scholar 

  11. V. Bermúdez, F. Bermúdez, G. Acosta, A. Acosta, J. Añez, C. Andara, E. Leal, C. Cano, V. Manuel, R. Hernández, Z. Israili, Molecular mechanisms of endothelial dysfunction: from nitric oxide synthesis to ADMA inhibition. Am. J. Ther. 15, 326–333 (2008)

    Article  PubMed  Google Scholar 

  12. R.H. Böger, R. Maas, F. Schulze, E. Schwedhelm, Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality—an update on patient populations with a wide range of cardiovascular risk. Pharmacol. Res. 60, 481–487 (2009)

    Article  PubMed  Google Scholar 

  13. A.E. Altinova, M. Arslan, A. Sepici-Dincel, M. Akturk, N. Altan, F.B. Toruner, Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations. J. Clin. Endocrinol. Metab. 92, 1881–1885 (2007)

    Article  CAS  PubMed  Google Scholar 

  14. E.P. Wijekoon, M.E. Brosnan, J.T. Brosnan, Homocysteine metabolism in diabetes. Biochem. Soc. Trans. 35, 1175–1179 (2007)

    Article  CAS  PubMed  Google Scholar 

  15. M. Wolf, L. Sandler, K. Hsu, K. Vossen-Smirnakis, J.L. Ecker, R. Thadhani, First-trimester C-reactive protein and subsequent gestational diabetes. Diabetes Care 26, 819–824 (2003)

    Article  CAS  PubMed  Google Scholar 

  16. C. Zoccali, F.A. Benedetto, R. Maas, F. Mallamaci, G. Tripepi, L.S. Malatino, R. Böger, CREED Investigators, Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J. Am. Soc. Nephrol. 13, 490–496 (2002)

    Article  CAS  PubMed  Google Scholar 

  17. K. Krzyzanowska, F. Mittermayer, M. Wolzt, G. Schernthaner, Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care 30, 1834–1839 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. F. Mittermayer, B.X. Mayer, A. Meyer, C. Winzer, G. Pacini, O.F. Wagner, M. Wolzt, A. Kautzky-Willer, Circulating concentrations of asymmetrical dimethyl-L-arginine are increased in women with previous gestational diabetes. Diabetologia 45, 1372–1378 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. F. Mittermayer, A. Kautzky-Willer, C. Winzer, K. Krzyzanowska, T. Prikoszovich, S. Demehri, O. Wagner, M. Wolzt, Elevated concentrations of asymmetric dimethylarginine are associated with deterioration of glucose tolerance in women with previous gestational diabetes mellitus. J. Intern. Med. 261, 392–398 (2007)

    Article  CAS  PubMed  Google Scholar 

  20. B. Telejko, A. Zonenberg, M. Kuzmicki, A. Modzelewska, K. Niedziolko-Bagniuk, A. Ponurkiewicz, A. Nikolajuk, M. Gorska, Circulating asymmetric dimethylarginine, endothelin-1 and cell adhesion molecules in women with gestational diabetes. Acta Diabetol. 46, 303–308 (2009)

    Article  CAS  PubMed  Google Scholar 

  21. B.M. Chen, L.W. Xia, R.Q. Zhao, Determination of N(G), N(G)-dimethylarginine in human plasma by high-performance liquid chromatography. J. Chromatogr. B 692, 467–471 (1997)

    Article  CAS  Google Scholar 

  22. G.A. Knock, A.L. McCarthy, C. Lowy, L. Poston, Association of gestational diabetes with abnormal maternal vascular endothelial function. Br. J. Obstet. Gynaecol. 104, 229–234 (1997)

    CAS  PubMed  Google Scholar 

  23. K.Y. Lin, A. Ito, T. Asagami, P.S. Tsao, S. Adimoolam, M. Kimoto, H. Tsuji, G.M. Reaven, J.P. Cooke, Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106, 987–992 (2002)

    Article  CAS  PubMed  Google Scholar 

  24. A. Biri, A. Onan, E. Devrim, F. Babacan, M. Kavutcu, I. Durak, Oxidant status in maternal and cord plasma and placental tissue in gestational diabetes. Placenta 27, 327–332 (2006)

    Article  CAS  PubMed  Google Scholar 

  25. H.O. Steinberg, H. Chaker, R. Leaming, A. Johnson, G. Brechtel, A.D. Baron, Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J. Clin. Invest. 97, 2601–2610 (1996)

    Article  CAS  PubMed  Google Scholar 

  26. A.D. Baron, H.O. Steinberg, H. Chaker, R. Leaming, A. Johnson, G. Brechtel, Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J. Clin. Invest. 96, 786–792 (1995)

    Article  CAS  PubMed  Google Scholar 

  27. A.D. Baron, J.S. Zhu, S. Marshall, O. Irsula, G. Brechtel, C. Keech, Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats. Am. J. Physiol. 269, 709–715 (1995)

    Google Scholar 

  28. K. Sydow, C.E. Mondon, J. Schrader, H. Konishi, J.P. Cooke, Dimethylarginine dimethylaminohydrolase overexpression enhances insulin sensitivity. Arterioscler. Thromb. Vasc. Biol. 28, 692–697 (2008)

    Article  CAS  PubMed  Google Scholar 

  29. M. Wohlin, J. Sundstrom, J. Arnlov, B. Andren, B. Zethelius, L. Lind, Impaired insulin sensitivity is an independent predictor of common carotid intima-media thickness in a population sample of elderly men. Atherosclerosis 170, 181–185 (2003)

    Article  CAS  PubMed  Google Scholar 

  30. B. Idzior-Waluś, K. Cyganek, K. Sztefko, G. Seghieri, M.C. Breschi, M. Waluś-Miarka, E. Kawalec, M. Seretny, J. Sieradzki, Total plasma homocysteine correlates in women with gestational diabetes. Arch. Gynecol. Obstet. 278, 309–313 (2008)

    Article  PubMed  Google Scholar 

  31. M.A. Guven, M. Kilinc, C. Batukan, H.C. Ekerbicer, T. Aksu, Elevated second trimester serum homocysteine levels in women with gestational diabetes mellitus. Arch. Gynecol. Obstet. 274, 333–337 (2006)

    Article  CAS  PubMed  Google Scholar 

  32. E. Tarim, T. Bagis, E. Kilicdag, S. Erkanli, E. Aslan, N. Sezgin, E. Kuscu, Elevated plasma homocysteine levels in gestational diabetes mellitus. Acta Obstet. Gynecol. Scand. 83, 543–547 (2004)

    PubMed  Google Scholar 

  33. R.H. Böger, S.R. Lentz, S.M. Bode-Boger, H.R. Knapp, W.G. Haynes, Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans. Clin. Sci. 100, 161–167 (2001)

    Article  PubMed  Google Scholar 

  34. M.C. Stühlinger, P.S. Tsao, J.H. Her, M. Kimoto, R.F. Balint, J.P. Cooke, Homocysteine impairs the nitric oxide synthase pathway. Role of asymmetric dimethylarginine. Circulation 104, 2569–2575 (2001)

    Article  PubMed  Google Scholar 

  35. J.P. Kirwan, S. Hauguel-De Mouzon, J. Lepercq, J.C. Challier, L. Huston-Presley, J.E. Friedman, S.C. Kalhan, P.M. Catalano, TNF-a is a predictor of insulin resistance in human pregnancy. Diabetes 51, 2207–2213 (2002)

    Article  CAS  PubMed  Google Scholar 

  36. M. Wolf, J. Sauk, A. Shah, K. Vossen Smirnakis, R. Jimenez-Kimble, J.L. Ecker, R. Thadhani, Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus. Diabetes Care 27, 21–77 (2004)

    Article  PubMed  Google Scholar 

  37. H. Leipold, C. Worda, C.J. Gruber, T. Prikoszovich, O. Wagner, A. Kautzky-Willer, Gestational diabetes mellitus is associated with increased C-reactive protein concentrations in the third but not second trimester. Eur. J. Clin. Invest. 35, 752–757 (2005)

    Article  CAS  PubMed  Google Scholar 

  38. P. Valtonen, K. Punnonen, H. Saarelainen, N. Heiskanen, O.T. Raitakari, J.S. Viikari, T. Lyyra-Laitinen, T. Laitinen, S. Heinonen, Maternal serum ADMA is not associated with proinflammatory cytokines or C-reactive protein during normal pregnancy. Cytokine 46, 216–221 (2009)

    Article  CAS  PubMed  Google Scholar 

  39. V. Toescu, S.L. Nuttall, U. Martin, P. Nightingale, M.J. Kendall, P. Brydon, F. Dunne, Changes in plasma lipids and markers of oxidative stress in normal pregnancy and pregnancies complicated by diabetes. Clin. Sci. 106, 93–98 (2004)

    Article  CAS  PubMed  Google Scholar 

  40. M. Rizzo, K. Berneis, A.E. Altinova, F.B. Toruner, M. Akturk, G. Ayvaz, G.B. Rini, G.A. Spinas, M. Arslan, Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes. Diabet. Med. 25, 1406–1411 (2008)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge Assoc. Prof. Yasemin Genc and Zeynep Bıyıklı for their help in the statistical analysis.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara, Turkey

    Mujde Akturk & Metin Arslan

  2. Division of Endocrinology, Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey

    Alev Altinova

  3. Department of Perinatology, Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey

    Ismail Mert, Ayla Sargin & Nuri Danisman

  4. Department of Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey

    Aylin Dincel

  5. Division of Biochemistry, Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey

    Umran Buyukkagnici

  6. Bilkent University, Merkez Loj. 21/5, Bilkent, 06800, Ankara, Turkey

    Mujde Akturk

Authors
  1. Mujde Akturk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alev Altinova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ismail Mert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aylin Dincel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ayla Sargin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Umran Buyukkagnici
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Metin Arslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nuri Danisman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mujde Akturk.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akturk, M., Altinova, A., Mert, I. et al. Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes. Endocr 38, 134–141 (2010). https://doi.org/10.1007/s12020-010-9361-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-010-9361-1

Keywords

Search

Navigation