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Correlation of serum angiogenin level with various vascular complications in type 2 diabetic patients



Premature development of microvascular and macrovascular disease is the most frequent complication of diabetes. It is responsible for diabetic retinopathy, nephropathy, and neuropathy. Moreover, diabetes leads to reduced collateralization in ischemic tissues, which causes a three- to four-fold increase in cardiac mortality in diabetic individuals compared with nondiabetic individuals.

The pathophysiological mechanisms responsible for impaired angiogenic activity in diabetes remain unknown. The role of angiogenin in the physiological revascularization process has not been clarified.


This work was carried out to determine the serum angiogenin level in type 2 diabetic patients and to determine its correlation with various microangiopathies, cardiovascular complications, and the duration in type 2 diabetic patients.

Patients and methods

This work was carried out on 88 individuals, 68 type 2 diabetic patients and 20 apparently healthy controls. All individuals were subjected to the following assessments: medical history taking; clinical examination including measurement of BMI; estimation of levels of fasting blood sugar, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, low-density lipoprotein, and creatinine; determination of the albumin/creatinine ratio and complete lipid profile (total cholesterol, triglyceride, high-density lipoproteins); serum angiogenin estimation by enzyme linked immunosorbent assay; fundus examination; ECG and transthoracic echocardiography; and abdominal ultrasonography.


Our results indicated a significant decrease in the serum angiogenin level in diabetic patients compared with the control group; an insignificantly low serum angiogenin level in diabetic patients with retinopathy and nephropathy compared with those without retinopathy and nephropathy, respectively; a significant decrease in the serum angiogenin level in patients with coronary artery disease (CAD) compared with diabetic patients without CAD; an insignificant inverse correlation of angiogenin with fasting blood sugar, duration of diabetes mellitus with urea, and creatinine with albumin/creatinine ratio; and an insignificant proportional correlation of angiogenin with ejection fraction in diabetic patients with complications of retinopathy, nephropathy, and CAD in each group separately.


This work concluded that the serum angiogenin level is lower in type 2 diabetic patients compared with the control group and it decreases with prolonged duration of diabetes, especially in uncontrolled patients and patients with microangiopathic and cardiovascular complications.

As angiogenin is one of most powerful angiogenic factors, we recommend further studies to evaluate the diagnostic, prognostic, and therapeutic value of angiogenin in various microangiopathic and cardiovascular complications of type 2 diabetes.


  1. American Diabetes Association. 2009. All about diabetes. Available at: [Accessed 22 May 2009].

  2. Siebert J, Reiwer-Gostomska M, Babińska Z, Myśliwska J, Myśliwski A, Skopińska-Ró zewska E, et al. Low serum angiogenin concentrations in patients with type 2 diabetes. Diabetes Care 2007; 30:3087–3087.

    Article  Google Scholar 

  3. Siebert J, Reiwer-Gostomska M, Mysliwska J, Marek N, Raczynska K, Glasner L. Glycemic control influences serum angiogenin concentrations in patients with type 2 diabetes. Diabetes Care 2010; 33:1829–1830.

    Article  Google Scholar 

  4. Sodha NR, Clements RT, Boodhwani M, Xu S-H, Laham RJ, Bianchi C, Sellke FW. Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation. Am J Physiol Heart Circ Physiol 2009; 296:H428–H434.

    Article  CAS  Google Scholar 

  5. American Diabetes Association. Diagnosis and classification of diabetes mellitus [position statement]. Diabetes Care 2010; 33 (Suppl 1): S4–S10.

    Google Scholar 

  6. Weihrauch D, Lohr NL, Mraovic B, Ludwig LM, Chilian WM, Pagel PS, et al. Chronic hyperglycemia attenuates coronary collateral development and impairs proliferative properties of myocardial interstitial fluid by production of angiostatin. Circulation 2004; 109:2343–2348.

    Article  CAS  Google Scholar 

  7. Zorena K, Myśliwska J, Myśliwiec M, Balcerska A. Analysis of levels of angiogenin in children and adolescents with type 1 diabetes mellitus in relation to the duration of the disease. Int Rev Allergol Clin Immunol 2008; 14:3–4.

    Google Scholar 

  8. Suzumori N, Zhao XX, Suzumori K. Elevated angiogenin levels in the peritoneal fluid of women with endometriosis correlate with the extent of the disorder. Fertil Steril 2004; 82:93–96.

    Article  CAS  Google Scholar 

  9. Tello-Montoliu A, Patel JV, Lip GY. Angiogenin: a review of pathophysiology and potential clinical applications. J Thromb Haemost 2006; 4:1864–1874.

    Article  CAS  Google Scholar 

  10. Trouillon R, Kang D-K, Park H, Chang S-I, O’Hare D. Angiogenin induces nitric oxide synthesis in endothelial cells through PI-3 and Akt kinase. Biochemistry 2010; 49:3282–3288.

    Article  CAS  Google Scholar 

  11. Patel JV, Sosin M, Gunarathne A, Hussain I, Davis RC, Hughes EA, Lip GYH. Elevated angiogenin levels in chronic heart failure. Ann Med 2008; 40:474–479.

    Article  CAS  Google Scholar 

  12. Tello A, Mari F, Patel J. Plasma angiogenin levels in acute coronary syndromes: implications for prognosis. Eur Heart J 2007; 28:3006–3011.

    Article  Google Scholar 

  13. Stitt AW, McGoldrick C, Rice-McCaldin A, McCance DR, Glenn JV, Hsu DK, et al. Impaired retinal angiogenesis in diabetes: role of advanced glycation end products and galectin-3. Diabetes 2005; 53:857–794.

    Google Scholar 

  14. Siebert J, Reiwer-Gostomska M, Babinska Z, et al. Low serum angiogenin level concentrations in patients with type 2 diabetes. Diabetes Care 2007; 30:3086–3087.

    Article  CAS  Google Scholar 

  15. Stratton IM, Adler AI, Epidemiologista H, Neil AW, Matthews DR, Manley SE, et al. Vascular damage in impaired glucose tolerance: an unappreciated phenomenon? Curr Pharm Des 2009; 15:3417–3432.

    Article  Google Scholar 

  16. Stratton IM, Adler AI, Neil HAW, et al. Association of glycaemia with mac-rovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:405–412.

    Article  CAS  Google Scholar 

  17. Chahil TJ, Ginsberg HN. Diabetic dyslipidemia. Endocrinol Metab Clin North Am 2006; 35:491–510.

    Article  CAS  Google Scholar 

  18. Zeeuw D, Raz I. Albuminuria: a great risk marker, but an underestimated target in diabetes. Diabetes Care 2008; 31 (Suppl 2): S190–S193.

    Article  Google Scholar 

  19. Hohenstein B, Hausknecht B, Boehmer K, Riess R, Brekken RA, Hugo CPM. Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man. Kidney Int 2006; 69:1654–1661.

    Article  CAS  Google Scholar 

  20. Marek N, Raczyńska K, Siebert J, Myśliwiec M, Zorena K, Myśliwska J, et al. Decreased angiogenin concentration in vitreous and serum in proliferative diabetic retinopathy. Microvasc Res 2011; 82:1–5.

    Article  CAS  Google Scholar 

  21. Mena R, Pei Z, Chen B, Ma R, et al. Age-related change of serum angiogenic factor levels in patients with coronary artery disease. Acta Cardiol 2009; 64:735–740.

    Article  Google Scholar 

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Correspondence to Somayh S. Eissa.

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Ahmed, N.F., Eissa, S.S., Ali, A.A. et al. Correlation of serum angiogenin level with various vascular complications in type 2 diabetic patients. Egypt J Intern Med 24, 63–71 (2012).

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  • angiogenin
  • coronary artery disease
  • microangiopathy
  • type 2 diabetes mellitus