Tip 2 Diyabetli Hastalarda SGLT2 İnhibitörlerinin Hematolojik Parametreler Üzerindeki Etkileri: Retrospektif Bir Çalışma
Yıl 2024,
Cilt: 8 Sayı: 2, 154 - 162, 30.08.2024
Baris Karagün
,
Okan Sefa Bakıner
Öz
Amaç: SGLT2 (Sodyum-Glukoz Kotransporter 2) inhibitörleri, tip 2 diyabetes mellitus (DM) hastalarında kardiyovasküler olayları azaltmada ve böbrek sonuçlarını iyileştirmede önemli faydalar göstermiştir. Ancak, bu ilaçların hematopoez üzerindeki etkileri tam olarak anlaşılmamıştır. Bu çalışma, SGLT2 inhibitörlerinin tip 2 DM hastalarındaki hematokrit, eritrosit sayısı düzeyleri ve çeşitli hematolojik parametreler üzerindeki etkilerini araştırmayı amaçladı.
Gereç ve Yöntemler: Çalışmaya SGLT2 inhibitörleri kullanan toplam 116 tip 2 DM hastası dahil edilmiştir. Demografik ve klinik özellikler ile laboratuvar parametreleri, başlangıçta ve kontrol muayenelerinde toplanmıştır. Hastalar, aldıkları spesifik SGLT2 inhibitörüne (dapagliflozin veya empagliflozin) göre gruplandırılmış ve başlangıç ile kontrol değerleri arasında karşılaştırmalar yapılmıştır.
Sonuçlar: Çalışma, SGLT2 inhibitörleri kullanan hastalar arasında hematokrit ve eritrosit sayısı düzeylerinde başlangıç değerlerine kıyasla anlamlı bir artış olduğunu buldu (p=0.002; p<0.001). Bu artış, dapagliflozin ile tedavi edilen hastalara kıyasla empagliflozin ile tedavi edilen hastalarda daha belirgindi. Ayrıca, ortalama trombosit hacmi (MPV) ve kırmızı hücre dağılım genişliği (RDW) değerleri SGLT2 inhibitörü kullanımından sonra azaldı ve bu durum potansiyel olarak olumlu kardiyovasküler etkileri gösterebilir (p=0.038; p=0.005).
Sonuç: SGLT2 inhibitörleri, hematopoez üzerinde önemli etkiler göstererek DM hastalarında hematokrit ve eritrosit sayısı düzeylerinde artışa yol açar. Bu bulgular, SGLT2 inhibitörlerinin hematolojik etkilerini anlamamıza katkıda bulunur ve tip 2 DM hastalarında glisemik kontrolün ötesindeki potansiyel faydalarını vurgular. Bu bulguların altında yatan mekanizmaları ve klinik sonuçları açıklığa kavuşturmak için daha fazla araştırma gereklidir.
Kaynakça
-
1. Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson
SC, vd. SGLT2 mediates glucose reabsorption in the early proximal
tubule. J Am Soc Nephrol JASN. Ocak 2011;22(1):104-12.
-
2. DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic
and cardiovascular considerations of SGLT2 inhibition. Nat
Rev Nephrol. Ocak 2017;13(1):11-26.
-
3. Tang J, Ye L, Yan Q, Zhang X, Wang L. Effects of Sodium-Glucose
Cotransporter 2 Inhibitors on Water and Sodium Metabolism.
Front Pharmacol. 23 Şubat 2022;13:800490.
-
4. Dekkers CCJ, Sjöström CD, Greasley PJ, Cain V, Boulton
DW, Heerspink HJL. Effects of the sodium-glucose co-transporter-
2 inhibitor dapagliflozin on estimated plasma volume
in patients with type 2 diabetes. Diabetes Obes Metab.
2019;21(12):2667-73.
-
5. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca
MP, vd. SGLT2 inhibitors for primary and secondary prevention
of cardiovascular and renal outcomes in type 2 diabetes:
a systematic review and meta-analysis of cardiovascular outcome
trials. Lancet Lond Engl. 05 Ocak 2019;393(10166):31-9.
-
6. Pozzi A, Cirelli C, Merlo A, Rea F, Scangiuzzi C, Tavano E,
vd. Adverse effects of sodium-glucose cotransporter-2 inhibitors
in patients with heart failure: a systematic review and meta-
analysis. Heart Fail Rev. 01 Ocak 2024;29(1):207-17.
-
7. Packer M. Mechanisms of enhanced renal and hepatic erythropoietin
synthesis by sodium-glucose cotransporter 2 inhibitors.
Eur Heart J. 21 Aralık 2023;44(48):5027-35.
-
8. Scholtes RA, Muskiet MHA, van Baar MJB, Hesp AC, Greasley
PJ, Karlsson C, vd. Natriuretic Effect of Two Weeks of
Dapagliflozin Treatment in Patients With Type 2 Diabetes
and Preserved Kidney Function During Standardized Sodium
Intake: Results of the DAPASALT Trial. Diabetes Care.
2021;44(2):440-7.
-
9. Ekanayake P, Mudaliar S. Increase in hematocrit with SGLT-
2 inhibitors - Hemoconcentration from diuresis or increased
erythropoiesis after amelioration of hypoxia? Diabetes Metab
Syndr Clin Res Rev. 2023;17(2):102702.
-
10. Kocatepe K, Bayraktaroğlu T, Karagözoğlu1 K, Tekin S, Topaloğlu
Ö. Tip 2 Diyabetiklerde Sodyum Glukoz Transporter
2 İnhibisyonu İle Ortaya Çikan Hemokonsantrasyon Ne Kadar
Önemlidir?: Olgu Sunumu ve Literatürün Gözden Geçirilmesi.
İçinde 2024. Erişim Adresi: Http://Www.Temhk.Org/
-
11. Dai ZC, Chen JX, Zou R, Liang XB, Tang JX, Yao CW. Role
and mechanisms of SGLT-2 inhibitors in the treatment of diabetic
kidney disease. Front Immunol. 2023;14:1213473.
-
12. O’Neill J, Fasching A, Pihl L, Patinha D, Franzén S, Palm F.
Acute SGLT inhibition normalizes O2 tension in the renal
cortex but causes hypoxia in the renal medulla in anaesthetized
control and diabetic rats. Am J Physiol Renal Physiol.
2015;309(3):F227-234.
-
13. 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.
-
14. Mazer CD, Hare GMT, Connelly PW, Gilbert RE, Shehata N,
Quan A, vd. Effect of Empagliflozin on Erythropoietin Levels,
Iron Stores, and Red Blood Cell Morphology in Patients With
Type 2 Diabetes Mellitus and Coronary Artery Disease. Circulation.
2020;141(8):704-7.
-
15. Gangat N, Szuber N, Alkhateeb H, Al-Kali A, Pardanani
A, Tefferi A. JAK2 wild-type erythrocytosis associated with
sodium-glucose cotransporter 2 inhibitor therapy. Blood.
2021;138(26):2886-9.
-
16. Ghanim H, Abuaysheh S, Hejna J, Green K, Batra M, Makdissi
A, Chaudhuri A, Dandona P. Dapagliflozin Suppresses Hepcidin
And Increases Erythropoiesis. J Clin Endocrinol Metab.
2020;105(4):dgaa057.
-
17. Son M, Lee YS, Hong AR, Yoon JH, Kim HK, Kang HC,
vd. Improved Erythrocyte Deformability Induced by Sodium-
Glucose Cotransporter 2 Inhibitors in Type 2 Diabetic
Patients. Cardiovasc Drugs Ther. Şubat 2022;36(1):59-67.
-
18. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel
S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl
UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin,
Cardiovascular Outcomes, and Mortality in Type
2 Diabetes. N Engl J Med. 2015;373(22):2117-28.
-
19. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A,
Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL,
Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson
IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine
MS; DECLARE–TIMI 58 Investigators. Dapagliflozin and
Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med.
2019;380(4):347-357.
-
20. Heerspink Hiddo J.L., Stefánsson Bergur V., Correa-Rotter
Ricardo, Chertow Glenn M., Greene Tom, Hou Fan-Fan, vd.
Dapagliflozin in Patients with Chronic Kidney Disease. N
Engl J Med. 07 Ekim 2020;383(15):1436-46.
-
21. The EMPA-KIDNEY Collaborative Group, Herrington WG,
Staplin N, Wanner C, Green JB, Hauske SJ, vd. Empagliflozin
in Patients with Chronic Kidney Disease. N Engl J Med. 12
Ocak 2023;388(2):117-27.
-
22. Taşkaldıran I, Kuşkonmaz Ş, Çulha C. Use of Sodium Glucose
Co-Transporter 2 Inhibitor (SGLT2i) in Geriatric Population.
Türkiye Diyabet Ve Obezite Derg. 29 Ağustos 2021;5(2):158-
64.
-
23. Soyaltin UE, Çetinkalp Ş, Şimşir IY, Kandemir A, Seziş M.
A Sweet Dream with SGLT2 Inhibitors. Türkiye Diyabet Ve
Obezite Derg. 29 Ağustos 2021;5(2):237-40.
-
24. Kaneto H, Obata A, Kimura T, Shimoda M, Kinoshita T, Matsuoka
T aki, vd. Unexpected Pleiotropic Effects of SGLT2 Inhibitors:
Pearls and Pitfalls of This Novel Antidiabetic Class.
Int J Mol Sci. Ocak 2021;22(6):3062.
-
25. Yaribeygi H, Maleki M, Nasimi F, Butler AE, Jamialahmadi T,
Sahebkar A. Sodium-glucose co-transporter 2 inhibitors and
hematopoiesis. J Cell Physiol. 2022;237(10):3778-87.
-
26. Heyman SN, Armaly Z, Hamo-Giladi DB, Abassi Z. Novel
perspectives regarding the physiologic mechanisms by which
gliflozins induce reticulocytosis and erythrocytosis. Am J
Physiol Endocrinol Metab. 01 Kasım 2023;325(5):E621-3.
-
27. Gupta R, Gupta A, Shrikhande M, Tyagi K, Ghosh A, Misra A.
Marked erythrocytosis during treatment with sodium glucose
cotransporter-2 inhibitors-report of two cases. Diabetes Res
Clin Pract. Nisan 2020;162:108127.
-
28. Wang X, Fu R, Liu H, Ma Y, Qiu X, Dong Z. The effects of sodium
glucose co-transporter (SGLT) 2 inhibitors on hematocrit
levels: a systematic review and meta-analysis of randomized
controlled trials. Ann Palliat Med. Haziran 2021;10(6):6467-
81.
-
29. Korniluk A, Koper-Lenkiewicz OM, Kamińska J, Kemona H,
Dymicka-Piekarska V. Mean Platelet Volume (MPV): New
Perspectives for an Old Marker in the Course and Prognosis
of Inflammatory Conditions. Mediators Inflamm. 17 Nisan
2019;2019:1-14.
-
30. Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW,
Konkle B, vd. Mean platelet volume as a predictor of cardiovascular
risk: a systematic review and meta-analysis. J Thromb
Haemost JTH. Ocak 2010;8(1):148-56.
-
31. Danese E, Lippi G, Montagnana M. Red blood cell distribution
width and cardiovascular diseases. J Thorac Dis. Ekim
2015;7(10):E402.
-
32. Symeonidis A, Kouraklis-Symeonidis A, Psiroyiannis A, Leotsinidis
M, Kyriazopoulou V, Vassilakos P, vd. Inappropriately
low erythropoietin response for the degree of anemia in
patients with noninsulin-dependent diabetes mellitus. Ann
Hematol. Şubat 2006;85(2):79-85.
Effects of SGLT2 Inhibitors on Hematologic Parameters in Patients with Type 2 Diabetes Mellitus: A Retrospective Study
Yıl 2024,
Cilt: 8 Sayı: 2, 154 - 162, 30.08.2024
Baris Karagün
,
Okan Sefa Bakıner
Öz
Aim: SGLT2 (Sodium-Glucose Cotransporter 2) inhibitors have demonstrated significant benefits in reducing cardiovascular events and improving renal outcomes in patients with type 2 diabetes mellitus (DM). However, their effects on hematopoiesis are not fully understood. This study aimed to investigate the impact of SGLT2 inhibitors on hematocrit, erythrocyte count levels, and various hematologic parameters in patients with type 2 DM
Methods: A total of 116 patients with type 2 DM using SGLT2 inhibitors were included in the study. Demographic and clinical characteristics, as well as laboratory parameters, were collected at baseline and during control examinations. The patients were stratified based on the specific SGLT2 inhibitor received (dapagliflozin or empagliflozin), and comparisons were made between baseline and control values.
Results: The study found a significant increase in hematocrit and erythrocyte count levels among patients using SGLT2 inhibitors compared to baseline values (p=0.002; p<0.001). This increase was more pronounced in patients treated with empagliflozin compared to dapagliflozin. Additionally, mean platelet volume (MPV) and red cell distribution width (RDW) values decreased following SGLT2 inhibitor use, potentially indicating favorable cardiovascular effects (p=0.038; p=0.005).
Conclusion: SGLT2 inhibitors exert significant effects on hematopoiesis, leading to increased hematocrit and erythrocyte count levels in patients with DM. These findings contribute to our understanding of the hematologic effects of SGLT2 inhibitors and highlight their potential benefits beyond glycemic control in patients with type 2 DM. Further research is warranted to elucidate the underlying mechanisms and clinical implications of these findings.
Kaynakça
-
1. Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson
SC, vd. SGLT2 mediates glucose reabsorption in the early proximal
tubule. J Am Soc Nephrol JASN. Ocak 2011;22(1):104-12.
-
2. DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic
and cardiovascular considerations of SGLT2 inhibition. Nat
Rev Nephrol. Ocak 2017;13(1):11-26.
-
3. Tang J, Ye L, Yan Q, Zhang X, Wang L. Effects of Sodium-Glucose
Cotransporter 2 Inhibitors on Water and Sodium Metabolism.
Front Pharmacol. 23 Şubat 2022;13:800490.
-
4. Dekkers CCJ, Sjöström CD, Greasley PJ, Cain V, Boulton
DW, Heerspink HJL. Effects of the sodium-glucose co-transporter-
2 inhibitor dapagliflozin on estimated plasma volume
in patients with type 2 diabetes. Diabetes Obes Metab.
2019;21(12):2667-73.
-
5. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca
MP, vd. SGLT2 inhibitors for primary and secondary prevention
of cardiovascular and renal outcomes in type 2 diabetes:
a systematic review and meta-analysis of cardiovascular outcome
trials. Lancet Lond Engl. 05 Ocak 2019;393(10166):31-9.
-
6. Pozzi A, Cirelli C, Merlo A, Rea F, Scangiuzzi C, Tavano E,
vd. Adverse effects of sodium-glucose cotransporter-2 inhibitors
in patients with heart failure: a systematic review and meta-
analysis. Heart Fail Rev. 01 Ocak 2024;29(1):207-17.
-
7. Packer M. Mechanisms of enhanced renal and hepatic erythropoietin
synthesis by sodium-glucose cotransporter 2 inhibitors.
Eur Heart J. 21 Aralık 2023;44(48):5027-35.
-
8. Scholtes RA, Muskiet MHA, van Baar MJB, Hesp AC, Greasley
PJ, Karlsson C, vd. Natriuretic Effect of Two Weeks of
Dapagliflozin Treatment in Patients With Type 2 Diabetes
and Preserved Kidney Function During Standardized Sodium
Intake: Results of the DAPASALT Trial. Diabetes Care.
2021;44(2):440-7.
-
9. Ekanayake P, Mudaliar S. Increase in hematocrit with SGLT-
2 inhibitors - Hemoconcentration from diuresis or increased
erythropoiesis after amelioration of hypoxia? Diabetes Metab
Syndr Clin Res Rev. 2023;17(2):102702.
-
10. Kocatepe K, Bayraktaroğlu T, Karagözoğlu1 K, Tekin S, Topaloğlu
Ö. Tip 2 Diyabetiklerde Sodyum Glukoz Transporter
2 İnhibisyonu İle Ortaya Çikan Hemokonsantrasyon Ne Kadar
Önemlidir?: Olgu Sunumu ve Literatürün Gözden Geçirilmesi.
İçinde 2024. Erişim Adresi: Http://Www.Temhk.Org/
-
11. Dai ZC, Chen JX, Zou R, Liang XB, Tang JX, Yao CW. Role
and mechanisms of SGLT-2 inhibitors in the treatment of diabetic
kidney disease. Front Immunol. 2023;14:1213473.
-
12. O’Neill J, Fasching A, Pihl L, Patinha D, Franzén S, Palm F.
Acute SGLT inhibition normalizes O2 tension in the renal
cortex but causes hypoxia in the renal medulla in anaesthetized
control and diabetic rats. Am J Physiol Renal Physiol.
2015;309(3):F227-234.
-
13. 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.
-
14. Mazer CD, Hare GMT, Connelly PW, Gilbert RE, Shehata N,
Quan A, vd. Effect of Empagliflozin on Erythropoietin Levels,
Iron Stores, and Red Blood Cell Morphology in Patients With
Type 2 Diabetes Mellitus and Coronary Artery Disease. Circulation.
2020;141(8):704-7.
-
15. Gangat N, Szuber N, Alkhateeb H, Al-Kali A, Pardanani
A, Tefferi A. JAK2 wild-type erythrocytosis associated with
sodium-glucose cotransporter 2 inhibitor therapy. Blood.
2021;138(26):2886-9.
-
16. Ghanim H, Abuaysheh S, Hejna J, Green K, Batra M, Makdissi
A, Chaudhuri A, Dandona P. Dapagliflozin Suppresses Hepcidin
And Increases Erythropoiesis. J Clin Endocrinol Metab.
2020;105(4):dgaa057.
-
17. Son M, Lee YS, Hong AR, Yoon JH, Kim HK, Kang HC,
vd. Improved Erythrocyte Deformability Induced by Sodium-
Glucose Cotransporter 2 Inhibitors in Type 2 Diabetic
Patients. Cardiovasc Drugs Ther. Şubat 2022;36(1):59-67.
-
18. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel
S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl
UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin,
Cardiovascular Outcomes, and Mortality in Type
2 Diabetes. N Engl J Med. 2015;373(22):2117-28.
-
19. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A,
Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL,
Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson
IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine
MS; DECLARE–TIMI 58 Investigators. Dapagliflozin and
Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med.
2019;380(4):347-357.
-
20. Heerspink Hiddo J.L., Stefánsson Bergur V., Correa-Rotter
Ricardo, Chertow Glenn M., Greene Tom, Hou Fan-Fan, vd.
Dapagliflozin in Patients with Chronic Kidney Disease. N
Engl J Med. 07 Ekim 2020;383(15):1436-46.
-
21. The EMPA-KIDNEY Collaborative Group, Herrington WG,
Staplin N, Wanner C, Green JB, Hauske SJ, vd. Empagliflozin
in Patients with Chronic Kidney Disease. N Engl J Med. 12
Ocak 2023;388(2):117-27.
-
22. Taşkaldıran I, Kuşkonmaz Ş, Çulha C. Use of Sodium Glucose
Co-Transporter 2 Inhibitor (SGLT2i) in Geriatric Population.
Türkiye Diyabet Ve Obezite Derg. 29 Ağustos 2021;5(2):158-
64.
-
23. Soyaltin UE, Çetinkalp Ş, Şimşir IY, Kandemir A, Seziş M.
A Sweet Dream with SGLT2 Inhibitors. Türkiye Diyabet Ve
Obezite Derg. 29 Ağustos 2021;5(2):237-40.
-
24. Kaneto H, Obata A, Kimura T, Shimoda M, Kinoshita T, Matsuoka
T aki, vd. Unexpected Pleiotropic Effects of SGLT2 Inhibitors:
Pearls and Pitfalls of This Novel Antidiabetic Class.
Int J Mol Sci. Ocak 2021;22(6):3062.
-
25. Yaribeygi H, Maleki M, Nasimi F, Butler AE, Jamialahmadi T,
Sahebkar A. Sodium-glucose co-transporter 2 inhibitors and
hematopoiesis. J Cell Physiol. 2022;237(10):3778-87.
-
26. Heyman SN, Armaly Z, Hamo-Giladi DB, Abassi Z. Novel
perspectives regarding the physiologic mechanisms by which
gliflozins induce reticulocytosis and erythrocytosis. Am J
Physiol Endocrinol Metab. 01 Kasım 2023;325(5):E621-3.
-
27. Gupta R, Gupta A, Shrikhande M, Tyagi K, Ghosh A, Misra A.
Marked erythrocytosis during treatment with sodium glucose
cotransporter-2 inhibitors-report of two cases. Diabetes Res
Clin Pract. Nisan 2020;162:108127.
-
28. Wang X, Fu R, Liu H, Ma Y, Qiu X, Dong Z. The effects of sodium
glucose co-transporter (SGLT) 2 inhibitors on hematocrit
levels: a systematic review and meta-analysis of randomized
controlled trials. Ann Palliat Med. Haziran 2021;10(6):6467-
81.
-
29. Korniluk A, Koper-Lenkiewicz OM, Kamińska J, Kemona H,
Dymicka-Piekarska V. Mean Platelet Volume (MPV): New
Perspectives for an Old Marker in the Course and Prognosis
of Inflammatory Conditions. Mediators Inflamm. 17 Nisan
2019;2019:1-14.
-
30. Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW,
Konkle B, vd. Mean platelet volume as a predictor of cardiovascular
risk: a systematic review and meta-analysis. J Thromb
Haemost JTH. Ocak 2010;8(1):148-56.
-
31. Danese E, Lippi G, Montagnana M. Red blood cell distribution
width and cardiovascular diseases. J Thorac Dis. Ekim
2015;7(10):E402.
-
32. Symeonidis A, Kouraklis-Symeonidis A, Psiroyiannis A, Leotsinidis
M, Kyriazopoulou V, Vassilakos P, vd. Inappropriately
low erythropoietin response for the degree of anemia in
patients with noninsulin-dependent diabetes mellitus. Ann
Hematol. Şubat 2006;85(2):79-85.