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Erschienen in: International Journal of Diabetes in Developing Countries 2/2019

02.08.2018 | Original Article

Serum Angiopoietin-2 levels as a marker in type 2 diabetes mellitus complications

verfasst von: Khalid Siddiqui, Salini Scaria Joy, Shaik Sarfaraz Nawaz

Erschienen in: International Journal of Diabetes in Developing Countries | Ausgabe 2/2019

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Abstract

Angiopoietin-2 (Ang-2) has been reported to be involved in the development of type 2 diabetes (T2D) and accelerates micro and macro vascular complication. The current study aimed to investigate serum Ang-2 levels in Saudi patients with type 2 diabetes and its complications. In this observational cross-sectional study, serum was collected from 329 T2D subjects aged 34–79 years. All subjects were evaluated for fasting blood glucose (FBG), HbA1c, lipid profile, and kidney profile. Serum concentration of Ang-2 was assayed by ELISA-based method. Mean serum Ang-2 level was significantly higher in female T2D subjects (2881 ± 1550 pg/ml) compared with male T2D subjects (2450 ± 1477 pg/ml). The mean serum Ang-2 levels in female T2D subjects significantly increased with increase in their age and BMI, while mean serum Ang-2 levels did not significantly increase among the male with their age and BMI. A significantly higher level of Ang-2 was found in patients with diabetic complications like neuropathy (3293 ± 1728 pg/ml), retinopathy (2986 ± 1645 pg/ml), and vascular complications (3152 ± 1571 pg/ml). The study has established comprehensive Ang-2 levels in various subsets of adults with diabetes. While interpreting Ang-2 levels, the differences in age and sex need to be taken into account. Diabetic patients with higher Ang-2 levels should be monitored closely and level of serum Ang-2 should be served as a marker to identify patients at high risk of diabetic complications.
Literatur
2.
Zurück zum Zitat Fowler MJ. Microvascular and macrovascular complications of diabetes. Clinical diabetes. 2008;26:77–82.CrossRef Fowler MJ. Microvascular and macrovascular complications of diabetes. Clinical diabetes. 2008;26:77–82.CrossRef
5.
Zurück zum Zitat Lee KW, Lip GY, Blann AD. Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes. Circulation. 2004;110:2355–60.CrossRefPubMed Lee KW, Lip GY, Blann AD. Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes. Circulation. 2004;110:2355–60.CrossRefPubMed
6.
Zurück zum Zitat Eklund L, Olsen BR. Tie receptors and their angiopoietin ligands are context-dependent regulators of vascular remodeling. Exp Cell Res. 2006;312:630–41.CrossRefPubMed Eklund L, Olsen BR. Tie receptors and their angiopoietin ligands are context-dependent regulators of vascular remodeling. Exp Cell Res. 2006;312:630–41.CrossRefPubMed
7.
Zurück zum Zitat Yancopoulos GD, Davis S, Gale NW, Rudge JS. Vascular-specific growth factors and blood vessel formation. Nature. 2000;407:242–8.CrossRefPubMed Yancopoulos GD, Davis S, Gale NW, Rudge JS. Vascular-specific growth factors and blood vessel formation. Nature. 2000;407:242–8.CrossRefPubMed
8.
Zurück zum Zitat Al-Rubeaan K, Siddiqui K, Al-Ghonaim MA, Youssef AM, Al-Sharqawi AH, AlNaqeb D. Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients. Sci Rep. 2017;7(1):2684.CrossRefPubMedPubMedCentral Al-Rubeaan K, Siddiqui K, Al-Ghonaim MA, Youssef AM, Al-Sharqawi AH, AlNaqeb D. Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients. Sci Rep. 2017;7(1):2684.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Abu El-Asrar AM, Mohammad G, Allegaert E, Ahmad A, Siddiquei MM, Alam K, et al. Opdenakker GMatrix metalloproteinase-14 is a biomarker of angiogenic activity in proliferative diabetic retinopathy. Mol Vis. 2018;24:394–406. eCollection 2018PubMedPubMedCentral Abu El-Asrar AM, Mohammad G, Allegaert E, Ahmad A, Siddiquei MM, Alam K, et al. Opdenakker GMatrix metalloproteinase-14 is a biomarker of angiogenic activity in proliferative diabetic retinopathy. Mol Vis. 2018;24:394–406. eCollection 2018PubMedPubMedCentral
11.
Zurück zum Zitat Maric-Bilkan C. Sex differences in micro-and macro-vascular complications of diabetes mellitus. Clin Sci. 2017;131:833–46.CrossRef Maric-Bilkan C. Sex differences in micro-and macro-vascular complications of diabetes mellitus. Clin Sci. 2017;131:833–46.CrossRef
12.
Zurück zum Zitat American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38:S8–S16.CrossRef American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38:S8–S16.CrossRef
13.
Zurück zum Zitat Early Treatment of Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic colour fundus photographs — an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology. 1991;98:786–806.CrossRef Early Treatment of Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic colour fundus photographs — an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology. 1991;98:786–806.CrossRef
14.
Zurück zum Zitat Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Li L, ZHeng-Qing Y, Juan-Yu H, Jian-Yong X, Fan L, Guang-Chun Z, et al. Association between interleukin-19 and angiopoietin-2 with vascular complications in type 2 diabetes. J Diabetes Investig. 2016;7:895–900.CrossRefPubMedPubMedCentral Li L, ZHeng-Qing Y, Juan-Yu H, Jian-Yong X, Fan L, Guang-Chun Z, et al. Association between interleukin-19 and angiopoietin-2 with vascular complications in type 2 diabetes. J Diabetes Investig. 2016;7:895–900.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Alissa EM, Bahjri SM, Al-Ama N, Ahmed WH, Ferns GA. High cardiovascular risk in young Saudi males: cardiovascular risk factors, diet and inflammatory markers. Clin Chim Acta. 2006;365:288–96.CrossRefPubMed Alissa EM, Bahjri SM, Al-Ama N, Ahmed WH, Ferns GA. High cardiovascular risk in young Saudi males: cardiovascular risk factors, diet and inflammatory markers. Clin Chim Acta. 2006;365:288–96.CrossRefPubMed
17.
Zurück zum Zitat Thomas M, Augustin HG. The role of the Angiopoietins in vascular morphogenesis. Angiogenesis. 2009;12:125–37.CrossRefPubMed Thomas M, Augustin HG. The role of the Angiopoietins in vascular morphogenesis. Angiogenesis. 2009;12:125–37.CrossRefPubMed
18.
Zurück zum Zitat Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277:55–60.CrossRefPubMed Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277:55–60.CrossRefPubMed
19.
Zurück zum Zitat Silha JV, Krsek M, Sucharda P, Murphy LJ. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes. 2005;29:1308–14.CrossRef Silha JV, Krsek M, Sucharda P, Murphy LJ. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes. 2005;29:1308–14.CrossRef
20.
Zurück zum Zitat Lieb W, Zachariah JP, Xanthakis V, Safa R, Chen MH, Sullivan LM, et al. Clinical and genetic correlates of circulating Angiopoietin-2 and soluble Tie-2 in the community. CircCardiovasc Genet. 2010;3:300–6.CrossRef Lieb W, Zachariah JP, Xanthakis V, Safa R, Chen MH, Sullivan LM, et al. Clinical and genetic correlates of circulating Angiopoietin-2 and soluble Tie-2 in the community. CircCardiovasc Genet. 2010;3:300–6.CrossRef
21.
Zurück zum Zitat Khalil RA. Sex hormones as potential modulators of vascular function in hypertension. Hypertension. 2005;46:249–54.CrossRefPubMed Khalil RA. Sex hormones as potential modulators of vascular function in hypertension. Hypertension. 2005;46:249–54.CrossRefPubMed
22.
Zurück zum Zitat Ardelt AA, McCullough LD, Korach KS, Wang MM, Munzenmaier DH, Hurn PD. Estradiol regulates angiopoietin-1 mRNA expression through estrogen receptor-alpha in a rodent experimental stroke model. Stroke. 2005;36:337–41.CrossRefPubMed Ardelt AA, McCullough LD, Korach KS, Wang MM, Munzenmaier DH, Hurn PD. Estradiol regulates angiopoietin-1 mRNA expression through estrogen receptor-alpha in a rodent experimental stroke model. Stroke. 2005;36:337–41.CrossRefPubMed
23.
Zurück zum Zitat Albrecht ED, Babischkin JS, Lidor Y, Anderson LD, Udoff LC, Pepe GJ. Effect of estrogen on angiogenesis in co-cultures of human endometrial cells and microvascular endothelial cells. Hum Reprod. 2003;18:2039–47.CrossRefPubMed Albrecht ED, Babischkin JS, Lidor Y, Anderson LD, Udoff LC, Pepe GJ. Effect of estrogen on angiogenesis in co-cultures of human endometrial cells and microvascular endothelial cells. Hum Reprod. 2003;18:2039–47.CrossRefPubMed
24.
Zurück zum Zitat Ye F, Florian M, Magder SA, Sabah NA. Hussain. Regulation of angiopoietin and Tie-2 receptor expression in nonreproductive tissues by estrogen. Steroids. 2002;67:305–10.CrossRefPubMed Ye F, Florian M, Magder SA, Sabah NA. Hussain. Regulation of angiopoietin and Tie-2 receptor expression in nonreproductive tissues by estrogen. Steroids. 2002;67:305–10.CrossRefPubMed
25.
Zurück zum Zitat Tahergorabi Z, Khazaei M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA Atheroscler. 2013;9:247–53.PubMedPubMedCentral Tahergorabi Z, Khazaei M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA Atheroscler. 2013;9:247–53.PubMedPubMedCentral
26.
Zurück zum Zitat Murdoch C, Muthana M, Lewis CE. Hypoxia regulates macrophage functions in inflammation. J Immunol. 2005;175:6257–63.CrossRefPubMed Murdoch C, Muthana M, Lewis CE. Hypoxia regulates macrophage functions in inflammation. J Immunol. 2005;175:6257–63.CrossRefPubMed
27.
Zurück zum Zitat Eder K, Baffy N, Falus A, Fulop AK. The major inflammatory mediator interleukin-6 and obesity. Inflamm Res. 2009;58:727–36.CrossRefPubMed Eder K, Baffy N, Falus A, Fulop AK. The major inflammatory mediator interleukin-6 and obesity. Inflamm Res. 2009;58:727–36.CrossRefPubMed
28.
Zurück zum Zitat Tuo QH, Zeng H, Stinnett A, Yu H, Aschner JL, Liao DF, et al. Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol. 2008;294:H2547–57.CrossRefPubMed Tuo QH, Zeng H, Stinnett A, Yu H, Aschner JL, Liao DF, et al. Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol. 2008;294:H2547–57.CrossRefPubMed
29.
Zurück zum Zitat Musaiger AO. Overweight and obesity in eastern mediterranean region: prevalence and possible causes. J Obes. 2011;2011:1–17.CrossRef Musaiger AO. Overweight and obesity in eastern mediterranean region: prevalence and possible causes. J Obes. 2011;2011:1–17.CrossRef
30.
Zurück zum Zitat Memish ZA, Bcheraoui CE, Tuffaha M, Robinson M, Daoud F, Jaber S, et al. Obesity and associated factors — Kingdom of Saudi Arabia, 2013. Prev Chronic Dis. 2014;11:140236.CrossRef Memish ZA, Bcheraoui CE, Tuffaha M, Robinson M, Daoud F, Jaber S, et al. Obesity and associated factors — Kingdom of Saudi Arabia, 2013. Prev Chronic Dis. 2014;11:140236.CrossRef
31.
Zurück zum Zitat Al-Malki JS, Al-Jaser MH, WarsyA S. Overweight and obesity in Saudi females of childbearing age. Int J Obes. 2003;27:134–9.CrossRef Al-Malki JS, Al-Jaser MH, WarsyA S. Overweight and obesity in Saudi females of childbearing age. Int J Obes. 2003;27:134–9.CrossRef
32.
Zurück zum Zitat Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, et al. Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. Cell Metab. 2009;10:178–88.CrossRefPubMed Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, et al. Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. Cell Metab. 2009;10:178–88.CrossRefPubMed
33.
Zurück zum Zitat Pugliese G, Pricci F, Romeo G, Pugliese F, Mene P, Giannini S, et al. Upregulation of mesangial growth factor and extracellular matrix synthesis by advanced glycation end products via a receptor-mediated mechanism. Diabetes. 1997;46:1881–7.CrossRefPubMed Pugliese G, Pricci F, Romeo G, Pugliese F, Mene P, Giannini S, et al. Upregulation of mesangial growth factor and extracellular matrix synthesis by advanced glycation end products via a receptor-mediated mechanism. Diabetes. 1997;46:1881–7.CrossRefPubMed
35.
Zurück zum Zitat Loukovaara S, Robciuc A, Holopainen JH, Lehti K, Pessi T, Liinamaa J, et al. Ang-2 upregulation correlates with increased levels of MMP-9, VEGF, EPO and TGFb1 in diabetic eyes undergoing vitrectomy. ActaOphthalmol. 2013;91:531–9. Loukovaara S, Robciuc A, Holopainen JH, Lehti K, Pessi T, Liinamaa J, et al. Ang-2 upregulation correlates with increased levels of MMP-9, VEGF, EPO and TGFb1 in diabetic eyes undergoing vitrectomy. ActaOphthalmol. 2013;91:531–9.
36.
Zurück zum Zitat Sivak JM, Fini ME. MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prig Retin Eye Res. 2002;21:1–14.CrossRef Sivak JM, Fini ME. MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prig Retin Eye Res. 2002;21:1–14.CrossRef
37.
Zurück zum Zitat Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996;87:1171–80.CrossRefPubMed Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996;87:1171–80.CrossRefPubMed
38.
Zurück zum Zitat Saharinen P, Bry M, Alitalo K. How do angiopoietins Tie in with vascular endothelial growth factors? CurrOpinHematol. 2010;17:198–205. Saharinen P, Bry M, Alitalo K. How do angiopoietins Tie in with vascular endothelial growth factors? CurrOpinHematol. 2010;17:198–205.
39.
Zurück zum Zitat Abu El-Asrar AM, Missotten L, Geboes K. Expression of hypoxia-inducible factor-1alpha and the protein products of its target genes in diabetic fibrovascularepiretinal membranes. Br J Ophthalmol. 2007;91:822–6.CrossRefPubMed Abu El-Asrar AM, Missotten L, Geboes K. Expression of hypoxia-inducible factor-1alpha and the protein products of its target genes in diabetic fibrovascularepiretinal membranes. Br J Ophthalmol. 2007;91:822–6.CrossRefPubMed
40.
Zurück zum Zitat Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol. 2006;27:552–8.CrossRefPubMed Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol. 2006;27:552–8.CrossRefPubMed
41.
Zurück zum Zitat Chong AY, Caine GJ, Freestone B, Blann AD, Lip GY. Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure. J Am CollCardiol. 2004;43:423–8.CrossRef Chong AY, Caine GJ, Freestone B, Blann AD, Lip GY. Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure. J Am CollCardiol. 2004;43:423–8.CrossRef
42.
Zurück zum Zitat Lim HS, Blann AD, Chong AY, Freestone B, Lip GY. Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes: implications for cardiovascular risk and effects of multifactorial intervention. Diabetes Care. 2004;27:2918–24.CrossRefPubMed Lim HS, Blann AD, Chong AY, Freestone B, Lip GY. Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes: implications for cardiovascular risk and effects of multifactorial intervention. Diabetes Care. 2004;27:2918–24.CrossRefPubMed
43.
Zurück zum Zitat Lim HS, Lip GY, Blann AD. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005;180:113–8.CrossRefPubMed Lim HS, Lip GY, Blann AD. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005;180:113–8.CrossRefPubMed
44.
Zurück zum Zitat Rasul S, Reiter MH, Ilhan A, Lampichler K, Wagner L, Kautzky-Willer A. Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study. Cardiovasc Diabetol. 2011;10:55.CrossRefPubMedPubMedCentral Rasul S, Reiter MH, Ilhan A, Lampichler K, Wagner L, Kautzky-Willer A. Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study. Cardiovasc Diabetol. 2011;10:55.CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Woolf AS, Gnudi L, Long DA. Roles of angiopoietins in kidney development and disease. J Am Soc Nephrol. 2009;20:239–44.CrossRefPubMed Woolf AS, Gnudi L, Long DA. Roles of angiopoietins in kidney development and disease. J Am Soc Nephrol. 2009;20:239–44.CrossRefPubMed
46.
Zurück zum Zitat Chang FC, Lai TS, Chiang CK, Chen YM, Wu MS, Chu TS, Wu KD, Lin SL. Angiopoietin-2 is associated with albuminuria and microinflammation in chronic kidney disease. PloS one. 2013;8(3):e54668.CrossRefPubMedPubMedCentral Chang FC, Lai TS, Chiang CK, Chen YM, Wu MS, Chu TS, Wu KD, Lin SL. Angiopoietin-2 is associated with albuminuria and microinflammation in chronic kidney disease. PloS one. 2013;8(3):e54668.CrossRefPubMedPubMedCentral
47.
Metadaten
Titel
Serum Angiopoietin-2 levels as a marker in type 2 diabetes mellitus complications
verfasst von
Khalid Siddiqui
Salini Scaria Joy
Shaik Sarfaraz Nawaz
Publikationsdatum
02.08.2018
Verlag
Springer India
Erschienen in
International Journal of Diabetes in Developing Countries / Ausgabe 2/2019
Print ISSN: 0973-3930
Elektronische ISSN: 1998-3832
DOI
https://doi.org/10.1007/s13410-018-0679-1

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