THE EFFECT OF LINAGLIPTIN ON ARRHYTHMIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Yıl 2024, Cilt: 25 Sayı: 2, 201 – 207, 29.04.2024

Oğuz Kaan Kaya , Gökhan Köker

https://doi.org/10.18229/kocatepetip.1195333

Öz

OBJECTIVE: Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that prevents the inactivation of incretin hormones and also stimulates the release of glucose-dependent insulin. Electrocardiographic abnormalities such as P wave dispersion and QT dispersion are associated with ventricular tachyarrhythmias and atrial fibrillation, respectively. In this study, we seek to determine if the introduction of linagliptin has any impact on the P wave dispersion and QT dispersion in individuals with Type 2 diabetes mellitus (Type 2 DM).
MATERIAL AND METHODS: The study included 60 random patients (28 females- 46.7 % , 18 hypertension- 30 %, 16 smokers- 26.7 % ) who were admitted to the Training and Research Hospital internal medicine policlinic between October 2019 and May 2021 and who started linagliptin. The patients’ electrocardiograms were taken at the start and the conclusion of the sixth month. Echocardiography was performed at treatment initiation and at the 6th month.
RESULTS: When basal and 6th month electrocardiograms were compared, significant changes were observed in P wave dispersion (0.0435 ± 0.014 – 0.0312 ± 0.011 p<0.01), QT interval dispersion (0.0496 ± 0.01 – 0.0402 ± 0.01 p<0.01) and QTc interval dispersion (0.051 ± 0.01 – 0.038 ± 0.14 p<0.01).
CONCLUSIONS: We demonstrated in this study that linagliptin had no detrimental effects on heart rhythm. Our study will be a guide for longer follow-up studies.

Anahtar Kelimeler

Dipeptidyl peptidase-4 (DPP-4) inhibitor, Type 2 diabetes mellitus, P wave dispersion, QT dispersion.

Kaynakça

• 1. International Diabetes Federation . IDF Diabetes Atlas, 6th edn, 2014 Update. Brussels, Belgium. http://www.idf.org/diabetesatlas. Date of access: 27 May 2013.
• 2. Inzucchi SE, Bergenstal RM, Buse JB, et al Management of hyperglycemia in type 2 diabetes, 2015: A patient‐centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38: 140–49.
• 3. Deeks DE. Linagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2012 10;72(13):1793-824.
• 4. Aroor AR, Sowers JR, Jia G, DeMarco VG. Pleiotropic effects of the Dipeptidyl peptidase-4 inhibitors on the cardiovascular system. Am J Physiol Heart Circ Physiol. 2014;(15):477–92.
• 5. Deacon CF, Holst JJ. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin Investig Drugs. 2010;19(1):133–40.
• 6. Tukek T, Akkaya V, Demirel S, Sozen AB, Kudat H, Atilgan et al. Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. Am J Cardiol. 2000;(85):896–99.
• 7. Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion. J Am Coll Cardiol. 2000;(36):1749-66.
• 8. Andrikopoulos GK, Dilaveris PE, Richter DJ, Gialafos EJ, Synetos AG, et al. Increased variance of P wave duration on the electrocardiogram distinguishes patients with idiopathic paroxysmal atrial fibrillation. Pacing Clin Electrophysiol. 2000;(23):1127-32.
• 9. Kawano S, Hiraoka M, Sawanobori T: Electrocardiographic features of p waves from patients with transient atrial fibrillation. Jpn Heart J. 1988:(29);57-67.
• 10. Dilaveris PE, Gialafos EJ, Sideris S, et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J. 1998;(135):733–38.
• 11. Garson A. How to measure the QT interval-What is normal? Am J Cardiol. 1993;(72):14-6.
• 12. Tse G, Lai ETH, Tse V, Yeo JM. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus. Journal of Diabetes Research 2016 Aug 23.
• 13. Celebi S, Celebi OO, Aydogdu S, Diker E. A peculiar medical cardioversion of atrial fibrillation with glucose infusion–a rare cause of atrial fibrillation: hypoglycemia. Am J Emerg Med. 2001;(29):134.
• 14. Benjamin EJ, Levy D, Vaziri SM, D'agostino RB, Belanger AJ, et al. Independent risk factors for atrial fibrillation in a population‐based cohort: the Framingham Heart Study. 1994;271(11):840‐44.
• 15. Schnabel RB, Sullivan LM, Levy D, Pencina MJ, Massaro JM, et al. Development of a risk score for atrial fibrillation (Framingham Heart Study): a community‐based cohort study. The Lancet. 2009;373(9665): 739‐ 45.
• 16. Soltysinska E, Speerschneider T, Winther SV, Thomsen MB. Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice. Cardiovascular Diabetology. 2014;13(1):122.
• 17. Nakao YM, Ueshima K, Nohara R, Mizunuma Y, Segawa I, et al. Holter monitoring for the screening of cardiac disease in diabetes mellitus: The non‐invasive Holter monitoring observation of new cardiac events in diabetics study. Diabetes and Vascular Disease Research. 2015; 12(6): 396‐404.
• 18. Simon F, Bette L, Dean RC, Robyn N, et al. NICE‐Sugar Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012; (367):1108‐1118.
• 19. Nordin C. The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidence. Diabetologia. 2010;53(8): 1552‐61.
• 20. Chow E, Bernjak A, Williams S, Fawdry RA, Hibbert S, et al. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk. Diabetes. 2014; 63(5): 1738‐47.
• 21. Zhang Y, Han H, Wang J, Wang H, Yang B, et al. Impairment of human ether à‐go‐go‐related gene (HERG) K+ channel function by hypoglycemia and hyperglycemia. Similar phenotypes but different mechanisms. Journal of Biological Chemistry. 2003;278(12):10417‐26.
• 22. Jermendy G, Toth L, Voros P, Perenyi J, Kammerer L, et al (1991). Prospective study of cardiac autonomic neuropathy in diabetes mellitus (Review) (in Hungarian). Orv Hetil . 1991;23 (25):1351–58.
• 23. Stevens MJ, Raffel DM, Allman KC, Dayanikli F, Ficaro E, et al(1998). Cardiac sympathetic dysinnervation in diabetes: implications for enhanced cardiovascular risk. Circulation. 98(10):961–68.
• 24. Schnell O, Hammer K, Muhr-Becker D, Ziegler A, Weiss M, et al (2002). Cardiac sympathetic dysinnervation in Type 2 diabetes mellitus with and without ECG-based cardiac autonomic neuropathy. J Diabetes Complications. 2002;16(3):220–27.
• 25. Fusilli L, Lyons M, Patel B, et al. Ventricular vulnerability in diabetes and myocardial norepinephrine release. Am J Med Sci. 1998;298(4):207–14.
• 26. Jermendy G, Toth L, Voros P, Koltai MZ, Pogatsa G. Cardiac autonomic neuropathy and QT interval length. A follow-up study in diabetic patients. Acta Cardiol. 1991; 46(2):189–200.
• 27. Ong JJ, Sarma JS, Venkataraman K, Levin SR, Singh BN. Circadian rhythmicity of heart rate and QTc interval in diabetic otonomic neuropathy: implications for the mechanism of sudden death. Am Heart J. 1993; 125(3):744–52.
• 28. Sharma SN (1992). Ventricular fibrillation with hypoglycemia. J Assoc Physicians India. 1992; 40(10):701.
• 29. Rydén L, Grant PJ, Anker SD, Berne C, Cosentino F, et al. ESC Guidelines on diabetes, pre‐diabetes, and cardiovascular diseases developed in collaboration with the EASD. European Heart Journal. 2013; 34(39): 3035‐87.

TİP 2 DİABETES MELLİTUSLU HASTALARDA LİNAGLİPTİN'İN ARİTMİ ÜZERİNE ETKİSİ

Yıl 2024, Cilt: 25 Sayı: 2, 201 – 207, 29.04.2024

Oğuz Kaan Kaya , Gökhan Köker

https://doi.org/10.18229/kocatepetip.1195333

Öz

AMAÇ: Linagliptin, inkretin hormonlarının inaktivasyonunu engelleyen ve ayrıca glukoza bağımlı insülin salınımını uyaran bir dipeptidil peptidaz-4 (DPP-4) inhibitörüdür. P dalga dispersiyonu ve QT dispersiyonu, atriyal fibrilasyon ve ventriküler taşiaritmilerle ilişkili elektrokardiyografik bulgulardır. Bu çalışmadaki amacımız, Tip 2 diabetes mellituslu (Tip 2 DM) hastalarda linagliptin uygulamasının P dalga dispersiyonu ve QT dispersiyonu üzerine bir etkisinin olup olmadığını araştırmaktır.
GEREÇ VE YÖNTEM: Çalışmaya Ekim 2019 – Mayıs 2021 tarihleri arasında Eğitim ve Araştırma Hastanesi dahiliye polikliniğine başvuran ve linagliptin başlanan 60 rastgele hasta (28 kadın- %46,7, 18 hipertansiyon- %30, 16 sigara içen- %26,7) dahil edildi. Hastaların 6. ayın başında ve sonunda elektrokardiyogramları çekildi. Hastaların linagliptin başlandığı anda ve 6. ayda ekokardiyografileri yapıldı.
BULGULAR: Bazal ve 6. ay elektrokardiyogramları karşılaştırıldığında, P dalga dispersiyonu (0.0435 ± 0.014 – 0.0312 ± 0.011 p<0.01), QT dispersiyonu (0.0496 ± 0.01 – 0.0402 ± 0.01 p<0.01) ve QTc dispersiyonunda ( 0.051 ± 0.01 – 0.038 ± 0.14 p<0.01) anlamlı değişiklikler olduğunu saptadık.
SONUÇ: Bu çalışmada linagliptinin aritmi üzerine olumsuz bir etkisinin olmadığını gösterdik. Çalışmamız daha uzun soluklu çalışmalar için yol gösterici olacaktır.

Anahtar Kelimeler

Dipeptidil peptidaz-4 (DPP-4) inhibitörü, Tip 2 diabetes mellitus, P dalga dispersiyonu, QT dispersiyonu.

Kaynakça

• 1. International Diabetes Federation . IDF Diabetes Atlas, 6th edn, 2014 Update. Brussels, Belgium. http://www.idf.org/diabetesatlas. Date of access: 27 May 2013.
• 2. Inzucchi SE, Bergenstal RM, Buse JB, et al Management of hyperglycemia in type 2 diabetes, 2015: A patient‐centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38: 140–49.
• 3. Deeks DE. Linagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2012 10;72(13):1793-824.
• 4. Aroor AR, Sowers JR, Jia G, DeMarco VG. Pleiotropic effects of the Dipeptidyl peptidase-4 inhibitors on the cardiovascular system. Am J Physiol Heart Circ Physiol. 2014;(15):477–92.
• 5. Deacon CF, Holst JJ. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin Investig Drugs. 2010;19(1):133–40.
• 6. Tukek T, Akkaya V, Demirel S, Sozen AB, Kudat H, Atilgan et al. Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. Am J Cardiol. 2000;(85):896–99.
• 7. Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion. J Am Coll Cardiol. 2000;(36):1749-66.
• 8. Andrikopoulos GK, Dilaveris PE, Richter DJ, Gialafos EJ, Synetos AG, et al. Increased variance of P wave duration on the electrocardiogram distinguishes patients with idiopathic paroxysmal atrial fibrillation. Pacing Clin Electrophysiol. 2000;(23):1127-32.
• 9. Kawano S, Hiraoka M, Sawanobori T: Electrocardiographic features of p waves from patients with transient atrial fibrillation. Jpn Heart J. 1988:(29);57-67.
• 10. Dilaveris PE, Gialafos EJ, Sideris S, et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J. 1998;(135):733–38.
• 11. Garson A. How to measure the QT interval-What is normal? Am J Cardiol. 1993;(72):14-6.
• 12. Tse G, Lai ETH, Tse V, Yeo JM. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus. Journal of Diabetes Research 2016 Aug 23.
• 13. Celebi S, Celebi OO, Aydogdu S, Diker E. A peculiar medical cardioversion of atrial fibrillation with glucose infusion–a rare cause of atrial fibrillation: hypoglycemia. Am J Emerg Med. 2001;(29):134.
• 14. Benjamin EJ, Levy D, Vaziri SM, D'agostino RB, Belanger AJ, et al. Independent risk factors for atrial fibrillation in a population‐based cohort: the Framingham Heart Study. 1994;271(11):840‐44.
• 15. Schnabel RB, Sullivan LM, Levy D, Pencina MJ, Massaro JM, et al. Development of a risk score for atrial fibrillation (Framingham Heart Study): a community‐based cohort study. The Lancet. 2009;373(9665): 739‐ 45.
• 16. Soltysinska E, Speerschneider T, Winther SV, Thomsen MB. Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice. Cardiovascular Diabetology. 2014;13(1):122.
• 17. Nakao YM, Ueshima K, Nohara R, Mizunuma Y, Segawa I, et al. Holter monitoring for the screening of cardiac disease in diabetes mellitus: The non‐invasive Holter monitoring observation of new cardiac events in diabetics study. Diabetes and Vascular Disease Research. 2015; 12(6): 396‐404.
• 18. Simon F, Bette L, Dean RC, Robyn N, et al. NICE‐Sugar Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012; (367):1108‐1118.
• 19. Nordin C. The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidence. Diabetologia. 2010;53(8): 1552‐61.
• 20. Chow E, Bernjak A, Williams S, Fawdry RA, Hibbert S, et al. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk. Diabetes. 2014; 63(5): 1738‐47.
• 21. Zhang Y, Han H, Wang J, Wang H, Yang B, et al. Impairment of human ether à‐go‐go‐related gene (HERG) K+ channel function by hypoglycemia and hyperglycemia. Similar phenotypes but different mechanisms. Journal of Biological Chemistry. 2003;278(12):10417‐26.
• 22. Jermendy G, Toth L, Voros P, Perenyi J, Kammerer L, et al (1991). Prospective study of cardiac autonomic neuropathy in diabetes mellitus (Review) (in Hungarian). Orv Hetil . 1991;23 (25):1351–58.
• 23. Stevens MJ, Raffel DM, Allman KC, Dayanikli F, Ficaro E, et al(1998). Cardiac sympathetic dysinnervation in diabetes: implications for enhanced cardiovascular risk. Circulation. 98(10):961–68.
• 24. Schnell O, Hammer K, Muhr-Becker D, Ziegler A, Weiss M, et al (2002). Cardiac sympathetic dysinnervation in Type 2 diabetes mellitus with and without ECG-based cardiac autonomic neuropathy. J Diabetes Complications. 2002;16(3):220–27.
• 25. Fusilli L, Lyons M, Patel B, et al. Ventricular vulnerability in diabetes and myocardial norepinephrine release. Am J Med Sci. 1998;298(4):207–14.
• 26. Jermendy G, Toth L, Voros P, Koltai MZ, Pogatsa G. Cardiac autonomic neuropathy and QT interval length. A follow-up study in diabetic patients. Acta Cardiol. 1991; 46(2):189–200.
• 27. Ong JJ, Sarma JS, Venkataraman K, Levin SR, Singh BN. Circadian rhythmicity of heart rate and QTc interval in diabetic otonomic neuropathy: implications for the mechanism of sudden death. Am Heart J. 1993; 125(3):744–52.
• 28. Sharma SN (1992). Ventricular fibrillation with hypoglycemia. J Assoc Physicians India. 1992; 40(10):701.
• 29. Rydén L, Grant PJ, Anker SD, Berne C, Cosentino F, et al. ESC Guidelines on diabetes, pre‐diabetes, and cardiovascular diseases developed in collaboration with the EASD. European Heart Journal. 2013; 34(39): 3035‐87.

Toplam 29 adet kaynakça vardır.

Ayrıntılar

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