Tip 2 Diabetes Mellitus Hastalarında Serum Endokan ve Adma Düzeylerinin Saptanması ve Diyabetin Komplikasyonları ile İlişkisinin Belirlenmesi

Year 2018, Volume: 2 Issue: 2, 49 - 58, 31.08.2018

Ayşegül Kalyon Muhammer Bilici , Dilek Arpacı , Taner Bayraktaroğlu

Abstract

Amaç: Endotel disfonksiyonun göstergesi olarak ADMA(Asimetrik Dimetilarginin) ve endokan ölçümünün kullanılabileceğine dair
çalışmalar mevcuttur. Bu çalışmada, diyabetik hastalarda serum endokan ile ADMA seviyeleri ölçülmüştür. Serum endokan ve ADMA
düzeyleri ile hiperglisemi bağlantılı mikrovasküler komplikasyonlar arasındaki ilişkinin değerlendirmesi amaçlanmıştır.

Gereç ve Yöntemler: Çalışmaya DM (Diabetes Mellitus) tanısı ile takipli ve rutin kontrole gelen 85 diyabetli ve bilinen sistemik hastalığı
olmayan 85 gönüllü (kontrol grubu) dahil edildi. Çalışmaya; akut enfeksiyon, malignite tanısı, diyaliz alma ve herhangi bir kronik
inflamatuvar hastalık öyküsü olanlar alınmadı. Diyabetiklerde diyabetik nefropati, nöropati ve retinopati ile serum ADMA ve endokan
düzeyi arasındaki ilişki incelendi. Hesaplanan p<0.05 düzeyleri istatistiksel olarak anlamlı kabul edildi.

Bulgular: Serum ADMA düzeyleri diyabetik olgu grubunda [9,42 (0,84-52,0)ng/ml]kontrol gruba [5,95(1,68-48,3)ng/ml] göre
anlamlı olarak daha yüksek saptanırken (p<0,001); diyabetiklerle [0,42(0,25-1,99ng/ml)] ve kontrol grubu [0,45(0,23-1,25)ng/ml]
arasında endokan düzeyleri arasında anlamlı fark saptanmadı (p=0,730). Mikrovasküler komplikasyonlu diyabetiklerle mikrovasküler
komplikasyonu olmayanlar arasında serum ADMA [sırasıyla 9,3(0,84-52,0)ng/ml; 9,4(3,1-51,3)ng/ml] ve endokan [sırasıyla 0,43(0,27-
1,87)ng/ml;0,41(0,25-1,99)ng/ml] düzeyleri açısından anlamlı fark bulunmadı (sırasıyla p=0,884 ve p=0,355). Diyabetik retinopati ve
nöropati saptananlar ile saptanmayanlar arasında serum ADMA ve endokan düzeyleri açısından anlamlı fark bulunmazken; proteinüri
saptananlarda saptanmayanlara göre serum ADMA ve endokan düzeyleri anlamlı derecede yüksek tespit edildi (sırasıyla p=0,04 ve
p=0,030).

Sonuç: Çalışmamız kronik düşük düzey inflamasyonun eşlik ettiği Tip 2 DM hastalarında vasküler disfonksiyon belirteci olarak serum
ADMA düzeylerinin kullanılabileceği hipotezini desteklemektedir. Ancak hastalık patofizyolojisinde yer alan inflamasyon göstergesi
olarak plazma endokan düzeyleri arasında ilişki bulunamakla birlikte serum ADMA ile endokan düzeylerinin birlikte ölçümünün
hastalık progresyonu öngörüsünde ek katkısının kısıtlı olduğu şeklindedir.

Keywords

Diabetes Mellitus, Endotel disfonksiyonu, Endokan, ADMA

Determination of Serum Endocan and ADMA Levels in Patients with Type 2 Diabetes Mellitus And Determination of Their Association With Diabetic Complications

Abstract

Aim: Diabetes mellitus (DM) is a chronic metabolic disease with a dramatic increase in prevalence. The current inflammatory process in
diabetes mellitus leads to differentiation of the vascular endothelium and consequently microvascular and macrovascular complications.
There are studies showing that ADMA and endocan measurement can be used as an endothelial dysfunction indicator. In this study, it was aimed to measure serum endocan and ADMA levels in diabetic patients and to evaluate the relationship between serum endocan
and ADMA levels and microvascular complications related to hyperglycemia.

Material and Methods: Eighty-five patients who were diagnosed with type 2 DM and 85 volunteers who did not have known systemic
disease were admitted to study. Those with acute infection, diagnosis of malignancy, history of dialysis treatment, and any chronic
inflammatory disease are not taken into account. Diabetic nephropathy, neuropathy, and retinopathy were screened in the patients.
The relationship between diabetic complications and serum ADMA and endocan levels was examined. Calculated p <0.05 levels were
considered statistically significant.

Results: Serum ADMA levels were significantly higher in the patient group [9,42 (0,84-52,0)ng/ml]when compared to the control
group[5,95(1,68-48,3)ng/ml] (p <0.001); but there was no significant difference between the patient[0,42(0,25-1,99ng/ml)] and control
group[0,45(0,23-1,25)ng/ml] in terms of endocan levels (p = 0.73). Serum ADMA [respectively 9,3(0,84-52,0)ng/ml; 9,4(3,1-51,3)and
endocan [respectively 0,43(0,27-1,87)ng/ml;0,41(0,25-1,99)ng/ml] levels were not significantly different in patients with microvascular
complications and without microvascular complications (p = 0.884 and p = 0.355, respectively). Serum ADMA and endocan levels
were not significantly different between patients who have diabetic retinopathy and neuropathy and patients who have not diabetic
retinopathy or neuropathy. Serum ADMA and endocan levels were found to be significantly higher in patients diagnosed with
proteinuria than in patients without proteinuria (p = 0.04 and p = 0.03, respectively).

Conclusion: Our study supports the hypothesis that serum ADMA levels may be used as a marker of vascular dysfunction in DM
patients with chronic low-level inflammation. However, since plasma endocan levels, which are an indicator of inflammation in the
pathophysiology of disease, cannot be correlated with microvascular complications, it can be interpreted that the additional contribution
of serum ADMA and endocan levels together is predictive of disease progression, limitedly.

Keywords

Diabetes Mellitus, Endothelial dysfunction, Endocan, ADMA

References

• 1. Satman İ, İmamoğlu Ş, Yılmaz C, Akalın S, Salman S, Dinççağ N. Diabetes Mellitus ve komplikasyonlarının tanı, tedavi ve izlem kılavuzu. Türkiye Endokrinoloji ve Metabolizma Derneği Ankara Erişim: http://temd.org.tr/admin/uploads/ tbl_kilavuz/20180516162547-2018-05-16tbl_kilavuz162544. pdf Erişim tarihi: 16-05-2018
• 2. Bilici M, Arpaci DK, Ilikhan SU, Corakci BD, Bayraktaroglu T, Arasli M, et al. Type 2 Diabetes Mellitus Associated with Premature Aging. Iranian Red Crescent Medical Journal. 2017;19(6).
• 3. Herder C, Bongaerts BW, Rathmann W, Heier M, Kowall B, Koenig W, et al. Association of subclinical inflammation with polyneuropathy in the older population: KORA F4 study. Diabetes Care. 2013;36(11):3663-70.
• 4. Hu H, Jiang H, Ren H, Hu X, Wang X, Han C. AGEs and chronic subclinical inflammation in diabetes: disorders of immune system. Diabetes/metabolism research and reviews. 2015;31(2):127-37.
• 5. Erbil MK, Kurt YG, Yaman H, Çakır E, Akgül EÖ, Çaycı T. Asimetrik dimetilarjininin metabolizması ve klinik önemi. Turkish Journal of Biochemistry/Turk Biyokimya Dergisi. 2012;37(1).
• 6. Sarrazin S, Adam E, Lyon M, Depontieu F, Motte V, Landolfi C, et al. Endocan or endothelial cell specific molecule-1 (ESM1): a potential novel endothelial cell marker and a new target for cancer therapy. Biochimica et Biophysica Acta (BBA)- Reviews on Cancer. 2006;1765(1):25-37.
• 7. Balta S, Mikhailidis DP, Demirkol S, Ozturk C, Celik T, Iyisoy A. Endocan: a novel inflammatory indicator in cardiovascular disease? Atherosclerosis. 2015;243(1):339-43.
• 8. Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman medical journal. 2012;27(4):269.
• 9. Rodríguez AJ, dos Santos Nunes V, Mastronardi CA, Neeman T, Paz-Filho GJ. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and metaanalysis of controlled cross-sectional studies. Journal of diabetes and its complications. 2016;30(2):357-67.
• 10. Hwang M-H, Kim S. Type 2 diabetes: endothelial dysfunction and exercise. Journal of exercise nutrition & biochemistry. 2014;18(3):239.
• 11. Temelkova-Kurktschiev T, Siegert G, Bergmann S, Henkel E, Koehler C, Jaro W, et al. Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes. MetabolismClinical and Experimental. 2002;51(6):743-9.
• 12. Dhananjayan R, Koundinya KS, Malati T, Kutala VK. Endothelial dysfunction in type 2 diabetes mellitus. Indian Journal of Clinical Biochemistry. 2016;31(4):372-9.
• 13. Özdoğu H. İnflamasyonda Bir Baş Aktör: Endotel.http://www. thd.org.tr/thdData/userfiles/file/6_IBK_03.pdf
• 14. Sena CM, Pereira AM, Seiça R. Endothelial dysfunction — A major mediator of diabetic vascular disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2013;1832(12):2216-31.
• 15. Aburawi EH, AlKaabi J, Zoubeidi T, Shehab A, Lessan N, Al Essa A, et al. Subclinical Inflammation and Endothelial Dysfunction in Young Patients with Diabetes: A Study from United Arab Emirates. PLOS ONE. 2016;11(7):e0159808.
• 16. BUĞDAYCI G, SERİN E. Asimetrik Dimetilarginin (ADMA). Düzce Tıp Fakültesi Dergisi 2005; 2: 36-41
• 17. Yılmaz M, Eyileten T, Yenicesu M. Kronik böbrek hastalığında yeni bir oyuncu: Asimetrik dimetilarginin (ADMA). Türk Nefroloji Diyaliz ve Transplantasyon Dergisi. 2007;16(3):93- 101.
• 18. Işıklar ÖÖ, Mutaf I. Asimetrik dimetilarginin ve klinik önemi. Türk Klinik Biyokimya Derg. 2010;8(2):75-89.
• 19. Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G. ADMA, cardiovascular disease and diabetes. diabetes research and clinical practice. 2008;82:S122-S6.
• 20. Taşkıran B, Altun BU, Vardar SA, Demir AM, Karadağ ÇH, Altun A. Effect of Exercise on ADMA Level in Type 2 Diabetes Mellitus. Balkan Medical Journal. 2014;2012(1):62-7.
• 21. Abbasi F, Asagmi T, Cooke JP, Lamendola C, McLaughlin T, Reaven GM, et al. Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus. The American journal of cardiology. 2001;88(10):1201-3.
• 22. Konya H, Miuchi M, Satani K, Matsutani S, Yano Y, Tsunoda T, et al. Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus. World journal of experimental medicine. 2015;5(2):110.
• 23. Altınova AE, Arslan M. Endokrin hastalıklarda asimetrik dimetilarjinin (ADMA). Marmara Medical Journal. 2009;22(1):80-4.
• 24. Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation. 2002;106(8):987-92.
• 25. Assal HS, Younes K, Alsayed A, Hasan N, Ali AR. Asymmetric dimethylarginine (ADMA) and progression of nephropathy in patients with type 2 diabetes. Kidney. 2009;18(5):247.
• 26. Malecki MT, Undas A, Cyganek K, Mirkiewicz-Sieradzka B, Wolkow P, Osmenda G, et al. Plasma asymmetric dimethylarginine (ADMA) is associated with retinopathy in type 2 diabetes. Diabetes Care. 2007;30(11):2899-901.
• 27. Pitsavos C, Tampourlou M, Panagiotakos DB, Skoumas Y, Chrysohoou C, Nomikos T, et al. Association between lowgrade systemic inflammation and type 2 diabetes mellitus among men and women from the ATTICA study. The review of diabetic studies: RDS. 2007;4(2):98.
• 28. Kose M, Emet S, Akpinar TS, Kocaaga M, Cakmak R, Akarsu M, et al. Serum endocan level and the severity of coronary artery disease: a pilot study. Angiology. 2015;66(8):727-31.
• 29. Abu El-Asrar AM, Nawaz MI, De Hertogh G, Al-Kharashi AS, Van den Eynde K, Mohammad G, et al. The angiogenic biomarker endocan is upregulated in proliferative diabetic retinopathy and correlates with vascular endothelial growth factor. Current eye research. 2015;40(3):321-31.
• 30. Arman Y, Akpinar TS, Kose M, Emet S, Yuruyen G, Akarsu M, et al. Effect of glycemic regulation on endocan levels in patients with diabetes: a preliminary study. Angiology. 2016;67(3):239- 44.
• 31. Cikrikcioglu MA, Erturk Z, Kilic E, Celik K, Ekinci I, Yasin Cetin AI, et al. Endocan and albuminuria in type 2 diabetes mellitus. Renal failure. 2016;38(10):1647-53.