Çocukluk Çağı Tip 1 Diyabetes Mellituslu Hastalarda Serum Asimetrik Dimetil Arjinin (Adma ) Düzeyi ile Erken Endotel Hasarı Arasındaki İlişkinin Saptanması

Öz

Amaç: Asimetrik dimetil arginin (ADMA), metilenmiş arginin, endotelyal nitric oksit (NO) sentaz inhibitörüdür. NO daha önceden Endothelium-Derived Relaxing Faktörü olarak bilinen, vasküler endotelyumdan sentezlenen önemli vazoaktif mediatördür. ADMA, endotel fonksiyon bozukluğunun yeni bir belirteci ve endotelyal fonksiyon bozukluğu için yeni risk faktörüdür. ADMA’nın insülin direnci, hipertansiyon, diyabetes mellitus, hiperlipidemi gibi birçok kronik hastalıkta arttığı gösterilmiştir.Gereç ve Yöntemler: Çalışmaya T.C. Sağlık Bakanlığı Keçiören Eğitim ve Araştırma Hastanesi Çocuk Endokrinoloji polikliniğinde 2011- 2013 yılları arasında takip edilen Tip 1 Diyabetes Mellitus tanılı 39 hasta ve aynı yaş grubunda 31 kontrol alındı. Cinsiyet, yaş, ağırlık, boy, vücut kitle indeksi, sistolik ve diastolik kan basıncı, açlık kan şekeri düzeyleri ve diyabet süreleri hastaların dosyalarından kaydedildi. Total kolesterol, HDL kolesterol, trigliserid, ADMA düzeyleri, folat ve homosistein düzeyleri açısından her iki grup karşılaştırıldı.Bulgular: Hasta grubu ve kontrol grubunda boy, kilo ve VKİ, yaş ve cinsiyet, sistolik ve diastolik kan basıncı arasında istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05). Tip 1 DM grubunda ADMA düzeyi (0.7±0.4 μmol/L) kontrol grubundan (0.6±0.1 μmol/L) anlamlı yüksek saptandı (p=0,004). Hasta ve kontrol grubu arasında ortalama homosistein ve folat düzeyleri benzer olup aralarında istatistiksel olarak anlamlı fark saptanmadı (p=0.368 ve 0.0887, sırasıyla).Sonuç: Endotelyal hasar ile ADMA arasındaki ilişki tip 1 DM’da ADMA ölçümlerinin vasküler hasarlanmada bir ön belirteç olarak kullanılmasını sağlayacak ve vasküler komplikasyonların önlenmesine yardımcı olabilecektir.

Anahtar Kelimeler

• ADMA, Homosistein, Diabetes mellitus, Çocuk

An Assessment of the Correlation Between Serum Asymmetric Dimethylarginine and Early Endothelial Dysfunction in Patients with Type 1 Diabetes Mellitus

Öz

Objective: Asymmetric dimethylarginine (ADMA), a methylated L-arginine analog, is a major endogenous competitive inhibitor of Nitric oxide (NO). NO is an important critical vasoactive mediator synthesized by the vascular endothelium, previously referred to as endothelium-derived relaxing factor. ADMA is a novel risk factor and a novel statement of endothelial dysfunction. ADMA levels are clinically increased in several clinical conditions such as diabetes mellitus (DM), hypertension, insulin resistance syndrome, dyslipidemia. Material and Methods: Thirty-one healthy children and 39 patients with Type 1 DM diagnosis, routinely followed by Keçiören Training and Research Hospital Pediatric Endocrinology Clinic between 2011 and 2013 were included in the study. Gender, age, weight, height, body mass index (BMI), systolic and diastolic blood pressure, fasting blood sugar values and diabetes duration were obtained from patient files. Total cholesterol, HDL cholesterol, triglyceride, ADMA, HbA1c, folate and homocysteine levels were compared between the two groups. results: There were no significant differences between the Type 1 DM group and the control group with respect to age, gender, body mass index (BMI), systolic and diastolic blood pressure. Average ADMA level in the Type 1 DM patient group (0.7±0.4 µmol/L) was significantly higher than the control group (0.6±0.1 µmol/L) (p=0.004). The homocysteine and folate levels for the two groups were similar and the differences were not significant (p=0.368 and 0.887, respectively).conclusion: The relation between endothelium damage and ADMA may lead to follow up ADMA measurement values being used as a pre marker for vascular damage in type 1 diabetes, and in turn help in preventing vascular complications

Anahtar Kelimeler

• ADMA, Homocysteine, Diabetes mellitus, Children

Kaynakça

1. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000;20:2032-7.
2. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524-6.
3. Aldamiz-Echevarria L, Andrade F. Asymmetric dimethylarginine, endothelial dysfunction and renal disease. Int J Mol Sci 2012;13:11288-311.
4. Bouran G, Deftereos S, Tousoulis D, Giannopoulos G, Chatzis G, Tsounis D et al. Asymmetric Dimetylarginine (ADMA): A promosing biomarker for cardiovascular disease? Curr Top Med Chem 2013;13:180-200.
5. Abd El Dayem SM,  Battah AA,  El-Shehaby A,  El Bohy Ael M. Asymmetric dimethyl L-arginine, nitric oxide and cardiovascular disease in adolescent type 1 diabetics. J Pediatr Endocrinol Metab 2014;27:437-4.
6. Takaya J,  Tanabe Y,  Kuroyanagi Y,  Kaneko K. Asymmetric dimethylarginine is negatively correlated with hyperglycemia in children. Endocr J 2015;62:551-6.
7. Chan NN, Vallance P, Colhoun HM. Endothelium-dependent and -in- dependent vascular dysfunction in type 1 diabetes: Role of conventional risk factors, sex, and glycemic control. Arterioscler Thromb Vasc Biol 2003;23:1048-54.
8. Correa RC, Alfieri AB. Plasmatic nitric oxide, but not von Willebrand Factor, is an early marker of endothelial damage, in type 1 diabetes mellitus patients without microvascular complications. J Diabetes Complications 2003;17:264-8.

9. Wiltshire E, Thomas DW, Baghurst P, Couper J. Reduced total plasma homocystine in children and adolescents with type 1 diabetes. J Pediatr 2001;138: 888-93.
10. Pavia C, Ferrer I, Valls C, Artuch R, Colome C, Vilaseca MA. Total homocysteine in patients with type 1 diabetes. Diabetes Care 2000;23:84-7.
11. Atabek ME, Pirgon O, Karagozoglu E. Plasma homocysteine levels in children and adolescents with type 1 diabetes. Indian Pediatr 2006;43:401-7.
12. Wollesen F, Brattström L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cys- teine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int 1999;55:1028-35.
13. Vallance P. The asymmetrical dimethylarginine / dimethylarginine dimethylaminohydrolase pathway in the regulation of nitric oxide production. Clin Sci 2001;100:159-60.
14. Stühlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: Role of asymmetric dimethylarginine. Circulation 2001;104:2569-75.