Acta Diabetologica

, Volume 47, Issue 2, pp 119–124

Circulating vascular endothelial growth factor in the normo- and/or microalbuminuric patients with type 2 diabetes mellitus

  • Peter Kubisz
  • Peter Chudý
  • Ján Staško
  • Peter Galajda
  • Pavol Hollý
  • Robert Vyšehradský
  • Marián Mokáň
Original Article


Relationship between serum vascular endothelial growth factor (VEGF) level and parameters of endothelial injury and/or dysfunction in patients with diabetes mellitus type 2 with or without microalbuminuria was investigated. Eighty-four diabetic patients were divided in two subgroups (42 each): normoalbuminuric (NAU) and microalbuminuric (MAU). Forty-two blood donors were in control group. Serum VEGF and plasma von Willebrand factor, soluble thrombomodulin, plasminogen activator inhibitor 1, thrombin-activatable fibrinolysis inhibitor (TAFI) and tissue plasminogen activator (t-PA) were measured using enzyme-linked immunosorbent assay in all subjects. VEGF was significantly higher in NAU compared to controls. The difference between MAU and controls was not statistically significant, but there was a trend toward significance. Only TAFI correlated with VEGF in MAU. An observed significant increase of serum VEGF level already in NAU suggests that serum VEGF could be a sensitive predictor of endothelial dysfunction in type 2 diabetes.


VEGF Diabetes mellitus type 2 Endothelial dysfunction 


  1. 1.
    Schrijvers BF, Flyvbjerg A, De Vriese AS (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 65:2003–2017CrossRefPubMedGoogle Scholar
  2. 2.
    Wolf G, Ziyadeh FN (2007) Cellular and molecular mechanisms of proteinuria in diabetic nephropathy. Nephron Physiol 106:26–31CrossRefGoogle Scholar
  3. 3.
    Khamaisi M, Schrijvers BF, De Vriese AS et al (2003) The emerging role of VEGF in diabetic kidney disease. Nephrol Dial Transplant 18:1427–1430CrossRefPubMedGoogle Scholar
  4. 4.
    Flyvbjerg A (2000) Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease. Diabetologia 43:1205–1223CrossRefPubMedGoogle Scholar
  5. 5.
    Chiarelli F, Spagnoli A, Basciani F et al (2000) Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with type 1 diabetes mellitus: relation to glycaemic control and microvascular complications. Diabetes UK Diabet Med 17:650–656Google Scholar
  6. 6.
    Knöbl P, Schernthaner G, Schnack C et al (1993) Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36:1045–1050CrossRefPubMedGoogle Scholar
  7. 7.
    Santilli F, Spagnoli A, Mohn A et al (2001) Increased vascular endothelial growth factor serum concentrations may help to identify patients with onset of type 1 diabetes during childhood at risk for developing persistent microalbuminuria. J Clin Endocrinol Metab 86:3871–3876CrossRefPubMedGoogle Scholar
  8. 8.
    Hovind P, Tarnow L, Oestergaard PB et al (2000) Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy. Kidney Int 57(Suppl 75):S56–S61CrossRefGoogle Scholar
  9. 9.
    Wasada T, Kawahara R, Katsumori K et al (1998) Plasma concentration of immunoreactive vascular endothelial growth factor and its relation to smoking. Metabolism 47:27–30CrossRefPubMedGoogle Scholar
  10. 10.
    Blann AD, Belgore FM, McCollum CN et al (2002) Vascular endothelial growth factor (VEGF) and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or type II diabetes. Clin Sci 102:187–194CrossRefPubMedGoogle Scholar
  11. 11.
    Shimada K, Baba T, Neugebauer S et al (2002) Plasma vascular endothelial growth factor in Japanese Type 2 diabetic patients with and without nephropathy. J Diabetes Complications 16:386–390CrossRefPubMedGoogle Scholar
  12. 12.
    Kim NH, Kim KB, Kim DL et al (2004) Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in type 2 diabetes mellitus. Diabetes UK Diabet Med 21:545–551Google Scholar
  13. 13.
    Kim NH, Oh JH, Seo JA et al (2005) Vascular endothelial growth factor (VEGF) and soluble VEGF receptor FLT-1 in diabetic nephropathy. Kidney Int 67:167–177CrossRefPubMedGoogle Scholar
  14. 14.
    Cha DR, Kang YS, Han SY et al (2004) Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type II diabetic rats. J Endocrinol 183:183–194CrossRefPubMedGoogle Scholar
  15. 15.
    Heywood DM, Mansfield MW, Grant PJ (1996) Levels of von Willebrand factor, insulin resistance syndrome, and a common vWF gene polymorphism in non-insulin-dependent (type 2) diabetes mellitus. Diabet Med 13:720–725CrossRefPubMedGoogle Scholar
  16. 16.
    Collier A, Rumley A, Rumley AG et al (1992) Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. Diabetes 41:909–913CrossRefPubMedGoogle Scholar
  17. 17.
    Schmitz A, Ingerslev J (1990) Haemostatic measures in type 2 diabetic patients with microalbuminuria. Diabet Med 7:521–525CrossRefPubMedGoogle Scholar
  18. 18.
    Gabat S, Keller C, Kempe HP et al (1996) Plasma thrombomodulin: a marker for microvascular complications in diabetes mellitus. Vasa 25:233–241PubMedGoogle Scholar
  19. 19.
    Inukai T, Fujiwara Y, Tayama K et al (1996) Clinical significance of measurements of urinary and serum thrombomodulins in patients with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 33:99–104CrossRefPubMedGoogle Scholar
  20. 20.
    Nilsson TK, Hellsten G, Amiral J (1993) Plasma thrombomodulin concentrations in relation to cardiovascular risk factors in a population sample. Blood Coagul Fibrinolysis 4:455–458CrossRefPubMedGoogle Scholar
  21. 21.
    Yano Y, Kitagawa N, Gabazza EC et al (2003) Increased plasma thrombin-activatable fibrinolysis inhibitor levels in normotensive type 2 diabetic patients with microalbuminuria. J Clin Endocrinol Metab 88:736–741CrossRefPubMedGoogle Scholar
  22. 22.
    Gruden G, Cavallo-Perin P, Romagnoli R et al (1994) Prothrombin fragment 1 + 2 and antithrombin III-thrombin complex in microalbuminuric type 2 diabetic patients. Diabet Med 11:485–488CrossRefPubMedGoogle Scholar
  23. 23.
    Leurs PB, Stolk RP, Hamulyak K et al (2002) Tissue factor pathway inhibitor and other endothelium-dependent hemostatic factors in elderly individuals with normal or impaired glucose tolerance and type 2 diabetes. Diabetes Care 25:1340–1345CrossRefPubMedGoogle Scholar
  24. 24.
    Kario K, Matsuo T, Kobayashi H et al (1995) Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. Arterioscler Thromb Vasc Biol 15:1114–1120PubMedGoogle Scholar
  25. 25.
    Miccoli R, Giampietro O, Penno G et al (1989) ‘Microalbuminuria’ in type I (insulin-dependent) diabetic patients with and without retinopathy. Acta Diabetol Lat 26(2):163–170CrossRefPubMedGoogle Scholar
  26. 26.
    Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report. Diabetes Care 26(Suppl 1):S5–S20Google Scholar
  27. 27.
    Tütüncü NB, Gürlek A, Gedik O (2001) Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study. Acta Diabetol 38(4):157–161CrossRefPubMedGoogle Scholar
  28. 28.
    McLaren M, Elhadd TA, Greene SA et al (1999) Elevated plasma vascular endothelial cell growth factor and thrombomodulin in juvenile diabetic patients. Clin Apll Thromb Haemost 5:21–24CrossRefGoogle Scholar
  29. 29.
    Chaturvedi N, Fuller JH, Pokras F et al (2001) Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus: the influence of ACE inhibition. Diabet Med 18:288–294CrossRefPubMedGoogle Scholar
  30. 30.
    Sharp PS, Al-Mrayat M, Valabhji J et al (1998) Serum levels of vascular endothelial growth factor in diabetic subjects: the relationship with blood pressure. Diabetologica 41:984–985CrossRefGoogle Scholar
  31. 31.
    García de la Torre N, Rubio MA, Bordiú E et al (2008) Effects of weight loss after bariatric surgery for morbid obesity on vascular endothelial growth factor-A, adipocytokines, and insulin. J Clin Endocrinol Metab 93(11):4276–4281CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Peter Kubisz
    • 1
  • Peter Chudý
    • 1
  • Ján Staško
    • 1
  • Peter Galajda
    • 2
  • Pavol Hollý
    • 1
  • Robert Vyšehradský
    • 3
  • Marián Mokáň
    • 2
  1. 1.National Center of Hemostasis and Thrombosis, Jessenius Faculty of MedicineComenius UniversityMartinSlovakia
  2. 2.Clinic of Internal Medicine 1, Jessenius Faculty of MedicineComenius UniversityMartinSlovakia
  3. 3.Clinic of Pneumophthisiology, Jessenius Faculty of MedicineComenius UniversityMartinSlovakia

Personalised recommendations