Tip 2 Diyabetli Hastalarda Dapagliflozin Tedavisinin Trombosit Fonksiyonları ve İnflamasyon Üzerine Etkisi

Yıl 2019, Cilt: 45 Sayı: 3, 291 - 294, 01.12.2019

Mehmet Ali Eren , Çiğdem Cindoğlu , Burcu Dikeç Gökçe , Ali Gökçe , Tevfik Sabuncu

https://doi.org/10.32708/uutfd.616075

Cited By: 1

Öz

Dapagliflozin kardiyovasküler hastalıklarda güvenli ve yararlı olduğu gösterilen bir oral anti-diyabetik (OAD) ilaçtır. Dapagliflozinin kardiyovasküler olumlu etkilerinin kesin mekanizması tam olarak bilinmemektedir. Bu çalışmada, dapagliflozin kullanan hastalarda tedavinin trombosit fonksiyonunu gösteren ortalama trombosit hacmi (OTH) ve yeni inflamatuar belirteçler olan nötrofil lenfosit oranı (NLO) ve trombosit lenfosit oranı (TLO) üzerine etkilerini araştırmayı amaçladık. Daha önce OAD veya OAD+insülin tedavisi almakta iken tedaviye dapagliflozin eklenen, 18 yaş üstü tip 2 diyabeti olan hastaların dosyaları incelenerek, dapagliflozin tedavisi başlamadan önce ve tedaviden sonra 3-6 ay içindeki laboratuar verileri kaydedildi. Dapagliflozin tedavisi ile birlikte glukoz ve A1c değerleri anlamlı olarak azalırken (her iki p<0.001), hemoglobin, hematokrit ve NLO değerleri anlamlı olarak arttı (sırasıyla p=0.005, p=0.001 ve p=0.032). Ayrıca nötrofil sayısı anlamlı olarak artarken, lenfosit sayısı anlamlı olarak azaldı (p=0.029 ve p=0.019). Dapagliflozin etkili bir OAD olup vücuttaki inflamasyon üzerine etkileri bulunmaktadır. Bu etkinin nasıl ve neden olduğunun anlaşılmasına ihtiyaç vardır. 

Anahtar Kelimeler

Dapagliflozin, Ortalama Trombosit Hacmi, Nötrofil Lenfosit Oranı, Trombosit Lenfosit Oranı

The Effect of Dapagliflozin on Platelet Function and Inflammation in Type 2 Diabetes

Öz

Dapagliflozin is an oral anti-diabetic drug (OAD) that has been shown to be safe and useful in cardiovascular diseases. The exact mechanism of cardiovascular positive effects of dapagiflozin is not fully understood. In this study, we aimed to investigate the effects of dapagliflozin treatment on mean platelet volume (MPV) as the marker of platelet function, and neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) as new anti-inflammatory markers. Laboratory data were recorded before and 3-6 months after the treatment of patients with type 2 diabetes over age of 18 years who received dapagliflozin when receiving OAD or OAD + insulin. Glucose and A1c values were significantly decreased (both p <0.001) and hemoglobin, hematocrit and NLR values were significantly increased with dapagliflozin treatment (p=0.005, p=0.001 and p=0.032, respectively). In addition, neutrophil count increased significantly and lymphocyte count decreased significantly (p=0.029 and p=0.019). Dapagliflozin is an effective OAD and affects inflammation in the body. There is a need to understand how and why this effect occurs.

Anahtar Kelimeler

Dapagliflozin, Mean Platelet Volume, Neutrophil Lymphocyte Ratio, Platelet Lymphocyte Ratio

Kaynakça

• 1. American Diabetes Association. 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018;41(Suppl 1):73-85.
• 2. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018;61(12):2461-98.
• 3. Lipscombe L, Booth G, Butalia S, et al. Pharmacologic Glycemic Management of Type 2 Diabetes in Adults. Diabetes Canada Clinical Practice Guidelines Expert Committee. Can J Diabetes 2018;42(1):88-103.
• 4. Bailey CJ, Gross JL, Hennicken D, Iqbal N, Mansfield TA, List JF. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo- controlled 102-week trial. BMC Med 2013;11:43.
• 5. Plosker GL. Dapagliflozin: a review of its use in patients with type 2 diabetes. Drugs 2014;74(18):2191-209.
• 6. Bath PM, Butterworth RJ. Platelet size: measurement, physiology and vascular disease. Blood Coagul Fibrinolysis 1996;7(2):157–61.
• 7. Martin JF, Trowbridge EA, Salmon G, Plumb J. The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration. Thromb Res 1983;32(5):443–60.
• 8. Verdoia M, Schaffer A, Barbieri L, et al. Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease. Diabetes Metab 2015;41(4):304-11.
• 9. Imtiaz F, Shafique K, Mirza SS, Ayoob Z, Vart P, Rao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med 2012;5:2.
• 10. Li W, Liu Q, Tang Y. Platelet to lymphocyte ratio in the prediction of adverse outcomes after acute coronary syndrome: a meta-analysis. Sci Rep 2017;7:40426.
• 11. Atak B, Aktas G, Duman TT, Erkus E, Kocak MZ, Savli H. Diabetes control could through platelet-to-lymphocyte ratio in hemograms. Rev Assoc Med Bras (1992) 2019;65(1):38-42.
• 12. Persson F, Nyström T, Jørgensen ME, et al. Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study. Diabetes Obes Metab 2018;20(2):344-51.
• 13. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019;380(4):347-57.
• 14. Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations. Circulation 2016;133(24):2459–2502.
• 15. Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J 2015;36:2288–2296.
• 16. Santos-Gallego CG, Picatoste B, Badimon JJ. Pathophysiology of acute coronary syndrome, Curr Atheroscler Rep 2014;16:9.
• 17. Projahn D, Koenen RR. Platelets: key players in vascular inflammation, J Leukoc Bio 2012;92:1167-75.
• 18. de Maat MP, Bladbjerg EM, Drivsholm T, Borch-Johnsen K, Møller L, Jespersen J. Inflammation, thrombosis and atherosclerosis: results of the Glostrup study. J Thromb Haemost 2003;1(5):950-7.
• 19. Li Z, Xu X, Deng L, et al. Design, synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents. Bioorg Med Chem 2018;26(14):3947-52.
• 20. Vizioli L, Muscari S, Muscari A. The relationship of mean platelet volume with the risk and prognosis of cardiovascular diseases. Int J Clin Pract 2009;63:1509-15.
• 21. Bayram SM, Gürsoy G, Araz Güngör A, Güngör F, Atalay E. The relationship of mean platelet volume with microalbuminuriain type 2 diabetic patients. Turk J Med Sci 2016;46(2):251-8.
• 22. Kaya H, Ertaş F, İslamoğlu Y, et al. Association between neutrophil to lymphocyte ratio and severity of coronary artery disease. Clin Appl Thromb Hemost 2014;20(1):50-4.
• 23. Zuin M, Rigatelli G, Picariello C, et al. Correlation and prognostic role of neutrophil to lymphocyte ratio and SYNTAX score in patients with acute myocardial infarction treated with percutaneous coronary intervention: A six-year experience. Cardiovasc Revasc Med 2017;18(8):565-71.
• 24. Mertoglu C, Gunay M. Neutrophil-Lymphocyte ratio and Platelet-Lymphocyte ratio as useful predictive markers of prediabetes and diabetes mellitus. Diabetes Metab Syndr 2017;11(1):127-31.
• 25. Li X, Shen J, Lu Z, Chen M, Fang X, Wang G. High neutrophil-to-lymphocyte ratio is associated with increased carotid artery intima-media thickness in type 2 diabetes. J Diabetes Investig 2017;8(1):101-107.
• 26. DiGangi C. Neutrophil-lymphocyte ratio: Predicting cardiovascular and renal complications in patients with diabetes. J Am Assoc Nurse Pract 2016;28(8):410-4.
• 27. Balta S, Ozturk C.The platelet-lymphocyte ratio: A simple, inexpensive and rapid prognostic marker for cardiovascular events. Platelets 2015;26(7):680-1.
• 28. Akboga MK, Canpolat U, Yayla C, et al. Association of Platelet to Lymphocyte Ratio With Inflammation and Severity of Coronary Atherosclerosis in Patients With Stable Coronary Artery Disease. Angiology 2016;67(1):89-95.
• 29. Hudzik B, Szkodzinski J, Gorol J, et al. Platelet-to-lymphocyte ratio is a marker of poor prognosis in patients with diabetes mellitus and ST-elevation myocardial infarction. Biomark Med 2015;9(3):199-207.
• 30. Jaikumkao, K, Pongchaidecha, A, Chueakula, N, et al. Dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, slows the progression of renal complications through the suppression of renal inflammation, endoplasmic reticulum stress and apoptosis in prediabetic rats. Diabetes Obes Metab. 2018;20:2617–26.
• 31. Ye Y, Bajaj M, Yang HC, Perez-Polo JR, Birnbaum Y. SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor. Cardiovasc Drugs Ther 2017;31(2):119-32.
• 32. Sa-Nguanmoo P, Tanajak P, Kerdphoo S,et al. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats. Toxicol Appl Pharmacol. 2017;333:43-50.
• 33. Díaz-Rodríguez E, Agra RM, Fernández ÁL, Adrio B, García-Caballero T, González-Juanatey JR, Eiras S. Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability. Cardiovasc Res 2018;114(2):336-46.
• 34. Solini A, Giannini L, Seghieri M, et al. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol 2017;16(1):138.
• 35. Sano M, Goto S. Possible Mechanism of Hematocrit Elevation by Sodium Glucose Cotransporter 2 Inhibitors and Associated Beneficial Renal and Cardiovascular Effects. Circulation. 2019;139(17):1985-7.