E-Selectin as an Early Atherosclerosis Marker in Prediabetes

Yıl 2019, Cilt: 52 Sayı: 2, 95 - 100, 31.07.2019

İlknur Öztürk Ünsal , Nujen Çolak Bozkurt , Evrim Çakır Mustafa Özbek Erman Çakal

Öz

Abstract

Background: Activation of endothelial dysfunction cascade and procoagulant pathways
are one of the main pathophysiological mechanisms that leads to beta cell
dysfunction, insulin resistance and vascular complications in prediabetes and
diabetes. The present study aimed to investigate the relation between
E-selectin and CIMT in prediabetic patients.

Methods:Seventy five
patients, who were diagnosed with prediabetes on 75gr oral glucose
tolerance test (OGTT) based on ADA criteria, were included in the present
study. Seventy five healthy volunteers were
included as the control group. The patient and the control groups were examined
in terms of E -selectin and fasting insulin levels. CIMT was measured by B-mode
ultrasonography and HOMA-IR was calculated.

Results: The mean E-selectin level was 35.19(9.56 – 118.46) ng/mL in the patient
group and 16.80(1.55 – 116.62) ng/mL in the control group. The difference
between the groups was statistically significant (P = 0.02). A significant
positive correlation was found between E-selectin and HbA1c (r= 0.292, P=0.014), and HOMA-IR (r= 0.301,P=0.011) in the
prediabetic group.

Conclusion: We found that E -selectin level, which is one of the markers of
endothelial dysfunction, was increased in prediabetes. This result supports the
idea that endothelial dysfunction and early stage atherosclerosis start in the
prediabetic period.

 

Özet

Amaç: Endotel
disfonksiyonu kaskadı ve prokoagülan yolaklarının aktivasyonu, prediyabet ve
diyabette beta hücre fonksiyon bozukluğuna, insülin direncine ve vasküler
komplikasyonlara yol açan ana patofizyolojik mekanizmalardan biridir. Bu
çalışmada prediyabetli hastalarda E-selektin ve CIMT arasındaki ilişkiyi
araştırmak amaçlanmıştır.

Yöntem: ADA
kriterlerine göre 75gr oral glukoz toleran testi (OGTT) ile prediyabet tanısı
konan 75 hasta çalışmaya dahil edildi. Yetmiş beş sağlıklı gönüllü de kontrol
grubu olarak değerlendirildi. Hasta ve kontrol grupları E-selektin ve açlık
insülin düzeyleri açısından incelendi. CIMT, B-mod ultrasonografi ile ölçüldü
ve HOMA-IR hesaplandı.

Bulgular: Hasta
grubunda ortalama E-selektin seviyesi 35.19 (9.56 - 118.46) ng / mL ve kontrol
grubunda 16.80 (1.55 - 116.62) ng / mL idi. Gruplar arasındaki fark
istatistiksel olarak anlamlıydı (P = 0,02). Prediyabetik grupta E-selektin ile
HbA1c (r = 0.292, P = 0.014) ve HOMA-IR (r = 0.301, P = 0.011) arasında anlamlı
bir ilişki bulundu.

Sonuç: Prediyabette
endotel disfonksiyonunun belirteçlerinden biri olan E-selektin düzeyinin
arttığını bulduk. Bu sonuç endotel disfonksiyonunun ve erken evre
aterosklerozun prediyabetik dönemde başladığı düşüncesini desteklemektedir.

Anahtar Kelimeler

prediabetes, atherosclerosis, e selectin

Kaynakça

• 1. IDF Diabetes Atlas. Eight edition, 2017
• 2. Gerstein HC, Santaguida P, Raina P, et al. Annualincidence and relative risk of diabetesin people with various categories of dysglycemia:a systematic overview and metaanalysisof prospective studies. Diabetes ResClin Pract 2007;78:305–312.
• 3. Chait A, Bornfeldt KE. Diabetes and atherosclerosis: is there a role forhyperglycemia? J Lipid Res 2009; 50: 335–339.
• 4. Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationshipbetween glucose and incident cardiovascular events. Diabetes Care 1999;22:233– 240.
• 5. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heartdisease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ 2006;332:73– 78.
• 6. Alexander CM, Landsman PB, Teutsch SM, Haffner SM, for theNHANES III and NCEP Investigators. NCEP-defined metabolicsyndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003;52:1210–1214.
• 7. Albelda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J. 1994;8:504–512.
• 8. Bevilacqua MP, Stengelin S, Gimbrone MA Jr, Seed B. Endothelialleukocyte adhesion molecule 1: an inducible receptor for neutrophils related tocomplement regulatory proteins and lectins. Science 1989;243: 1160–1165.
• 9. Dong ZM, Chapman SM, Brown AA, Frenette PS, Hynes RO, et al. The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 1998;102: 145– 152.
• 10. Ballantyne CM, Mainolfi EA, Young JB, Windsor NT, Cocanougher B, Lawrence EC, Pollack MS, Entman ML, Rothlein R. Relationship of increased levels of circulating intercellular adhesion molecule 1 after heart transplantation to rejection: human leukocyte antigen mismatch and survival. J Heart Lung Transplant. 1994;13:597–603.
• 11. Nakai K, Itoh C, Kawazoe K, Miura Y, Sotyanagi H, Hotta K, Itoh T, Kamata J, Hiramori K. Concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) correlated with expression of VCAM-1 mRNA in the human atherosclerotic aorta. Coron Artery Dis. 1996;6:497–502.
• 12. Gearing AJH, Newman W. Circulating adhesion molecules in disease. Immunol Today. 1993;14:506–512.
• 13. Blann AD, Farrell A, Picton A, McCollum CN. Relationship between endothelial cell markers and arterial stenosis in peripheral and carotid artery disease.Thromb Res. 2000; 97:209-216.
• 14. Blann AD, Amiral J, McCollum CN. Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease.Br J Haematol. 1996; 2:263-265.
• 15. Porta B, Baldassarre D, Camera M, Amato M, Arquati M, Brusoni B, Fiorentini C, Montorsi P, Romano S, et al. ; MIAMI Study Group. E-selectin and TFPI are associated with carotid intima-media thickness in stable IHD patients: the baseline findings of the MIAMI study. Nutr Metab Cardiovasc Dis. 2008;4:320-328.
• 16. Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto AM Jr, Boerwinkle. E Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. Circulation. 1997; 96:4219-4225.
• 17. Rho YH, Chung CP, Oeser A, et al. Novel cardiovascular riskfactors in premature coronary atherosclerosis associated with systemiclupus erythematosus. J Rheumatol 2008; 35: 1789–1794.
• 18. American Diabetes Association. Standards of Medical Care in Diabetes-2011. Diabetes Care. 2011; 34: 11–61.
• 19. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–419.
• 20. Gokcel A, Ozsahin AK, Sezgin N, Karakose H, Ertorer ME, Akbaba M, Baklaci N, Sengul A, Guvener N: High prevalence of diabetes in Adana, a southern province of Turkey. Diabetes Care 2003; 26:3031–3034.
• 21. Hingorani AD, Cross J, Kharbanda RK, Mullen MJ, Bhagat K, Taylor M, et al: Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 2000; 102:994–999.
• 22. Bacon PA, Raza K, Banks MJ, Townend J, Kitas GD: The role of endothelial cell dysfunction in the cardiovascular mortality of RA. Int Rev Immunol 2002; 21:1–17.
• 23. WangX, ZhangJ, DuX, SongM, Jia C,LiuH. Association of A561C and G98T Polymorphisms in ESelectinGene with Coronary Artery Disease: A Meta-Analysis. PLoS One. 2013; 8: 79301.
• 24. Squadrito F, Saitta A, Altavilla D, Ioculano M, Canale P, et al. Thrombolytic therapy with urokinase reduces increased circulating endothelialadhesion molecules in acute myocardial infarction. Inflamm Res 1996;45: 14–19.
• 25. Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotidatherosclerosis and incident coronary heart disease cases: the AtherosclerosisRisk In Communities (ARIC) study. Circulation 1996; 4219–4225.
• 26. Belch JJ, Shaw JW, Kirk G, McLaren M, Robb R, et al. The white bloodcell adhesion molecule E-selectin predicts restenosis in patients with intermittentclaudication undergoing percutaneous transluminal angioplasty. Circulation 1997;95:2027–2031.
• 27. Bluher M, Unger R, Rassoul F, Richter V, Paschke R. Relation betweenglycaemic control, hyperinsulinemia and plasma concentrations of solubleadhesion molecules in patients with impaired glucose tolerance or type IIdiabetes. Diabetologia. 2002;45:210–216.
• 28. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004;291:1978–1986.
• 29. Thorand B, Baumert J, Doring A, Schneider A, Chambless L, Lowel H, Kolb Koenig W. Association of cardiovascular risk factors with markers of endothelial dysfunction in middle-aged men and women. Results from the MONICA/KORA Augsburg Study. Thromb Haemost. 2006;95:134–141.
• 30. Vischer UM. von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost. 2006;4:1186–1193.
• 31. Tooke JE. Microvascular function in human diabetes. A physiological perspective.Diabetes. 1995;44:721–726.
• 32. Rossi R, Cioni E, Nuzzo A, Origliani G, Modena MG. Endothelial-dependent vasodilation and incidence of type 2 diabetes in a population of healthy postmenopausal women. Diabetes Care. 2005;28:702–707.
• 33. Meigs JB, O’Donnell CJ, Tofler GH, Benjamin EJ, Fox CS, Lipinska I, Nathan DM, Sullivan LM, D’Agostino RB, Wilson PW. Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes: the Framingham Offspring Study. Diabetes. 2006;55:530–537.
• 34. Lyon CJ, Law RE, Hsueh WA. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology. 2003;144:2195–2200.
• 35. Ferrannini E, Gastaldelli A, Iozzo P. Pathophysiology of prediabetes.Med Clin North Am 2011;95:327–339.
• 36. Tikellis G, Wang JJ, Tapp R, et al. The relationship of retinal vascular calibre to diabetes and retinopathy: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Diabetologia 2007;50:2263–2271.
• 37. Tapp RJ, Tikellis G, Wong TY, Harper CA, Zimmet PZ, Shaw JE; Australian Diabetes Obesity and Lifestyle Study Group. Longitudinal association of glucose metabolism with retinopathy: results from the Australian Diabetes Obesity and Lifestyle (AusDiab) study. Diabetes Care 2008;31:1349 –1354.
• 38. Sprague RS, Ellsworth ML. Vascular disease in pre-diabetes: new insights derived from systems biology. Mo Med 2010;107:265–269.
• 39. Singleton JR, Smith AG, Russell JW, Feldman EL. Microvascular complications of impaired glucose tolerance. Diabetes 2003;52:2867–2873.
• 40. Gabir MM, Hanson RL, Dabelea D, et al. Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes. Diabetes Care 2000;23:1113– 1118.
• 41. Franklin GM, Kahn LB, Baxter J, Marshall JA, Hamman RF. Sensory neuropathy in non-insulin-dependent diabetes mellitus. The San Luis Valley Diabetes Study. Am J Epidemiol 1990;131:633-643.
• 42. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997;96:1432-1437.
• 43. Knapp M, Lisowska A, Sobkowicz B, Tycińska A, Sawicki R, Musiał WJ. Myocardial perfusion and intima-media thickness in patients with subclinical hypothyroidism. Advances in Medical Sciences. 2013; 58: 44-49.·
• 44. Reynolds HR, Buyon J, Kim M, et al. Association of plasma soluble E-selectin and adiponectin with carotid plaque in patients with systemic lupus erythematosus. Atherosclerosis 2010; 210: 569–574.
• 45. Sakurai S1, Kitamura A, Cui R, Yamagishi K, Tanigawa T, Iso H. Relationships of soluble E-selectin and high-sensitivity C-reactive protein with carotid atherosclerosis in Japanese men. J Atheroscler Thromb. 2009; 16:339-345.