Öz
Amaç
Yeni tanı konmuş tip 2 diabetes mellitus (T2DM) hastalarında glutatyon peroksidaz (GPx), süperoksit dismutaz (SOD) ve total antioksidan kapasite (TAK) gibi antioksidanların düzeylerini incelemek ve oral antidiyabetikler ile insülin tedavisinin antioksidan moleküller ve ekokardiyografik ölçümler üzerindeki etkilerini karşılaştırmaktır.
Yöntem
Yeni tanı konmuş (son 4 hafta içinde tanı konmuş) T2DM 81 hasta antidiyabetik rejime göre 3 gruba ayrılmıştır (grup 1: Sadece metformin alan ve HbA1c <8,5, grup 2: Metformin artı vildagliptin alan ve HbA1c 8.5-10 arasında ve grup 3: Metformin artı vildagliptin artı premiks insülin alan ve HbA1c >10). Hastaların serum GPx, SOD, TAK düzeyleri ve ejeksiyon fraksiyonu (EF), sol ventrikül diyastol sonu kalınlığı (LVEDT) ve asendan aort çapı (AAD) gibi ekokardiyografik ölçümleri ilk vizitte ve çalışmanın 6. ayında incelenmiştir.
Bulgular
SOD, GPx ve TAC değerlerinin başlangıç ve 6. ay ortalamaları arasında 3 grupta istatistiksel olarak anlamlı bir fark bulunmazken, çalışma süresi boyunca ortalama SOD, GPx ve TAC seviyelerindeki azalma grup 1 hariç tüm gruplarda anlamlıydı. Grupların ekokardiyografik ölçümleri benzerdi ancak AAD’deki ortalama artış tüm gruplarda anlamlıydı ve aort çapındaki en düşük genişleme de sadece metformin grubundaydı. Çalışma süresi boyunca EF ve LVEDT’deki değişiklikler anlamlı değildi. Grup 1’de SOD ve AAD arasındaki korelasyon anlamlı bulunmuştur.
Sonuç
Metformin tedavisi, yeni tanı konmuş diyabet hastalarında SOD ve GPx seviyelerini korumakta ve AAD’deki genişleme, diğer kombinasyonlara kıyasla tekli metformin tedavisi ile en aza indirilmektedir. Ekokardiyografi parametreleri, asendan aort çapının DM’nin kardiyovasküler komplikasyonlarının güvenilir ve erken bir belirteci olduğunu ortaya koymuştur.
Anahtar Kelimeler:
Asendan aort çapı, glutatyon peroksidaz, metformin, süperoksit dismutaz, total antioksidan kapasite
Kaynaklar
1
Satman I, Omer B, Tutuncu Y, Kalaca S, Gedik S, Dinccag N, et al; TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013 b;28(2):169-180.
2
Vasan RS, Enserro DM, Xanthakis V, Beiser AS, Seshadri S. Temporal trends in the remaining lifetime risk of cardiovascular disease among middle-aged adults across 6 decades: the Framingham study. Circulation. 2022;145(17):1324-1338.
3
Heller GV. Evaluation of the patient with diabetes mellitus and suspected coronary artery disease. Am J Med. 2005;118(Suppl 2):9S-14S.
4
Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16(2):434-444.
5
Newsholme P, Cruzat VF, Keane KN, Carlessi R, de Bittencourt PI Jr. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J. 2016;473(24):4527-4550.
6
Kosova F, Altan N, Sepici A, Engin A, Kocamanoglu N. Thyroid hormones-mediated effects of insulin on antioxidant enzymes from diabetic rat hearts. Bratisl Lek Listy. 2013;114(4):183-188.
7
Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress- A concise review. Saudi Pharm J. 2016;24(5):547-553.
8
Scott LJ. Teriflunomide: a review in relapsing-remitting multiple sclerosis. Drugs. 2019;79(8):875-886.
9
Margis R, Dunand C, Teixeira FK, Margis-Pinheiro M. Glutathione peroxidase family - an evolutionary overview. FEBS J. 2008;275(15):3959-3970.
10
Parohan M, Anjom-Shoae J, Nasiri M, Khodadost M, Khatibi SR, Sadeghi O. Dietary total antioxidant capacity and mortality from all causes, cardiovascular disease and cancer: a systematic review and dose–response meta-analysis of prospective cohort studies. Eur J Nutr. 2019;58(6):2175-2189.
11
Helmut S. Total antioxidant capacity: appraisal of a concept. J Nutr. 2007;137(6):1493-1495.
12
Fang ZY, Schull-Meade R, Downey M, Prins J, Marwick TH. Determinants of subclinical diabetic heart disease. Diabetologia. 2005;48:394-402.
13
Hickson SS, Butlin M, Graves M IB, Taviani V, Avolio AP, McEniery CM, et al. The relationship of age with regional aortic stiffness and diameter. JACC Cardiovasc Imaging. 2010;3(12):1247-1255.
14
Nelson AJ, Worthley MI, Cameron JD. Regional differences in aortic geometry pathologic or compensatory? JACC Cardiovasc Imaging. 2011;4(5):562-563; author reply 563-564.
15
Günay Ş, Güllülü NS. Yaşlılarda aort anevrizmalarına yaklaşım [Approach to aortic aneurysms in the elderly]. Turk Kardiyol Dern Ars. 2017;45(Suppl 5):93-95. Turkish.
16
Clerc OF, Fuchs TA, Stehli J, Benz DC, Gräni C, Messerli M, et al. Non-invasive screening for coronary artery disease in asymptomatic diabetic patients: a systematic review and meta-analysis of randomised controlled trials. Eur Heart J Cardiovasc Imaging. 2018;19(8):838-846.
17
Singh H, Singh R, Singh A, Singh H, Singh G, Kaur S, et al. Role of oxidative stress in diabetes-induced complications and their management with antioxidants. Arch Physiol Biochem. 2024;130(6):616-641.
18
Hamamcıoğlu AC. The role of oxidative stres and antioxidants in diabetes. Turk J Diab Obes. 2017;1:7-13.
19
Kimura F, Hasegawa G, Obayashi H, Adachi T, Hara H, Ohta M, et al. Serum extracellular superoxide dismutase in patients with type 2 diabetes: relationship to the development of micro- and macrovascular complications. Diabetes Care. 2003;26(4):1246-1250.
20
Gómez-Marcos MA, Blázquez-Medela AM, Gamella-Pozuelo L, Recio-Rodriguez JI, García-Ortiz L, Martínez-Salgado C. Serum superoxide dismutase is associated with vascular structure and function in hypertensive and diabetic patients. Oxid Med Cell Longev. 2016;2016:9124676.
21
González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci. 2023;24(11):9352.
22
Pieme CA, Tatangmo JA, Simo G, Biapa Nya PC, Ama Moor VJ, Moukette Moukette B, et al. Relationship between hyperglycemia, antioxidant capacity and some enzymatic and non-enzymatic antioxidants in African patients with type 2 diabetes. BMC Res Notes. 2017;10(1):141.
23
Memisoğullari R, Taysi S, Bakan E, Capoglu I. Antioxidant status and lipid peroxidation in type II diabetes mellitus. Cell Biochem Funct. 2003;21(3):291-296.
24
Nobar M, Pour A, Nobar M, Beig F, Mirhashemi S. Total antioxidant capacity, süperoxide dismutase and glutathion peroxidase in diabetic patients. Medical Journal of Islamic Academy of Sciences. 1999;12(4):109-114.
25
Kumawat M, Sharma TK, Singh I, Singh N, Ghalaut VS, Vardey SK, et al. Antioxidant enzymes and lipid peroxidation in type 2 diabetes mellitus patients with and without nephropathy. N Am J Med Sci. 2013 5(3):213-219.
26
Rani AJ, Mythili SV. Study on total antioxidant status in relation to oxidative stress in type 2 diabetes mellitus. J Clin Diagn Res. 2014;8(3):108-110.
27
Wong FN, Chua KH, Tan JAMA, Wong CM, Kuppusamy UR. Glycaemic control in type 2 diabetic patients with chronic kidney disease: the impacts on enzymatic antioxidants and soluble RAGE. PeerJ. 2018;6:e4421.
28
Doddigarla Z, Parwez I, Ahmad J. Correlation of serum chromium, zinc, magnesium and SOD levels with HbA1c in type 2 diabetes: a cross sectional analysis. Diabetes Metab Syndr. 2016;10(1 Suppl 1):S126-S129.
29
Karam HM, Radwan RR. Metformin modulates cardiac endothelial dysfunction, oxidative stress and inflammation in irradiated rats: a new perspective of an antidiabetic drug. Clin Exp Pharmacol Physiol. 2019;46(12):1124-1132.
30
Altınkaynak SE. Tip 2 diabetes mellitus’lu hastalarda rosiglitazon veya metformin tedavisinin leptin, total antioksidan kapasite, süperoksit dismutaz, paraoksonaz ve lipid peroksidasyonu üzerindeki etkisinin incelenmesi. Gazi Üniversitesi Sağlık Bilimleri Enstitüsü Biyokimya Ana Bilim Dalı, Ankara, 2009.
31
Hatipoğlu H. The effects of metformin+insülin glargine and metformin+sitagliptin therapies on oxidative stres, antioxidants, paraoxonase, aryl esterase in patients with type 2 diabetes mellitus. Internal Medicine Speciality Thesis. Internal Medicine Department of Medical School of Harran University, Şanlıurfa, Turkey, 2010.
32
Ghavimi H, Sheidaei S, Vaez H, Zolali E, Asgharian P, Hamishehkar H. Metformin-attenuated sepsis-induced oxidative damages: a novel role for metformin. Iran J Basic Med Sci. 2018;21(5):469-475.
33
Dogan Turacli I, Candar T, Yuksel EB, Kalay S, Oguz AK, Demirtas S. Potential effects of metformin in DNA BER system based on oxidative status in type 2 diabetes. Biochimie. 2018;154:62-68.
34
Bartosz G. Non-enzymatic antioxidant capacity assays: Limitations of use in biomedicine. Free Radic Res. 2010;44(7):711-720.
35
Zhang Y, Xie YJ, Meng DD, Zhang HH, Chen H, Liu E. Clinical study of treatment switching from premixed insulin to basal insulin combined with oral hypoglycemic drugs in patients with type 2 diabetes. Diabetol Metab Syndr. 2014;6(1):37.
36
Scioli MG, Storti G, D’Amico F, Rodríguez Guzmán R, Centofanti F, Doldo E, et al. Oxidative stress and new pathogenetic mechanisms in endothelial dysfunction: potential diagnostic biomarkers and therapeutic targets. J Clin Med. 2020;9(6):1995.
37
Cooper JN, Buchanich JM, Youk A, Brooks MM, Barinas-Mitchell E, Conroy MB, et al. Reductions in arterial stiffness with weight loss in overweight and obese young adults: potential mechanisms. Atherosclerosis. 2012;223(2):485-490.
38
Vlachopoulos C, Alexopoulos N, Stefanadis C. Diabetes mellitus and aorta: does size matter? Cardiology. 2009;112(2):135-137.
39
Miao X, Wang Y, Sun J, Sun W, Tan Y, Cai L, et al. Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of metallothionein and nuclear factor (erythroid-derived 2)-like 2. Cardiovasc Diabetol. 2013;12:54.
40
Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, et al. Reduced ascending aortic strain and distensibility: earliest manifestations of vascular aging in humans. Hypertension. 2010;55(2):319-326.
41
Jensen MT, Fung K, Aung N, Sanghvi MM, Chadalavada S, Paiva JM, et al. Changes in cardiac morphology and function in individuals with diabetes mellitus: the UK biobank cardiovascular magnetic resonance substudy. Circ Cardiovasc Imaging. 2019;12(9):e009476.
42
Buczyńska A, Sidorkiewicz I, Krętowski AJ, Adamska A. Examining the clinical relevance of metformin as an antioxidant intervention. Front Pharmacol. 2024;15:1330797.
43
Kaya MG, Calapkorur B, Karaca Z, Yildirim S, Celik A, Akpek M, et al. The effects of treatment with drospirenone/ethinyl oestradiol alone or in combination with metformin on elastic properties of aorta in women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2012;77(6):885-892.
44
Bjornstad P, Schäfer M, Truong U, Cree-Green M, Pyle L, Baumgartner A, et al. Metformin improves insulin sensitivity and vascular health in youth with type 1 diabetes mellitus. Circulation. 2018;138(25):2895-2907.
45
Dallak M, Haidara MA, Bin-Jaliah I, Eid RA, Amin SN, Abdel Latif NS, et al. Metformin suppresses aortic ultrastrucural damage and hypertension induced by diabetes: a potential role of advanced glycation end products. Ultrastruct Pathol. 2019;43(4-5):190-198.
46
Sena CM, Matafome P, Louro T, Nunes E, Fernandes R, Seiça RM. Metformin restores endothelial function in aorta of diabetic rats. Br J Pharmacol. 2011;163(2):424-437.
47
Anderson JJA, Couper JJ, Giles LC, Leggett CE, Gent R, Coppin B, et al. Effect of metformin on vascular function in children with type 1 diabetes: a 12-month randomized controlled trial. J Clin Endocrinol Metab. 2017;102(12):4448-4456.
48
Petrie JR, Chaturvedi N, Ford I, Brouwers MCGJ, Greenlaw N, Tillin T, et al; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(8):597-609. Erratum in: Lancet Diabetes Endocrinol. 2017;5(8):e5. Erratum in: Lancet Diabetes Endocrinol. 2017;5(11):e7.
49
Gordin D, Saraheimo M, Tuomikangas J, Soro-Paavonen A, Forsblom C, Paavonen K, et al. Insulin exposure mitigates the increase of arterial stiffness in patients with type 2 diabetes and albuminuria: an exploratory analysis. Acta Diabetol. 2019;56(11):1169-1175.
50
Fu J, Yu MG, Li Q, Park K, King GL. Insulin’s actions on vascular tissues: physiological effects and pathophysiological contributions to vascular complications of diabetes. Mol Metab. 2021;52:101236.
51
Silvares RR, Pereira EN, Flores EE, Estato V, Reis PA, Silva IJ, et al. Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high-fat diet-/streptozotocin-induced diabetes. Int J Exp Pathol. 2016;97(3):266-277.
52
Lloyd S, Brocks C, Chatham JC. Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart. Am J Physiol Heart Circ Physiol. 2003;285(1):H163-H172.
53
Mannucci E, Targher G, Nreu B, Pintaudi B, Candido R, Giaccari A, et al; SID-AMD Joint Panel for Italian Guidelines on Treatment of Type 2 Diabetes. Effects of insulin on cardiovascular events and all-cause mortality in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. 2022;32(6):1353-1360.
54
Schernthaner G, Brand K, Bailey CJ. Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure. Metabolism. 2022;130:155160.
55
Park K, Li Q, Evcimen ND, Rask-Madsen C, Maeda Y, Maddaloni E, et al. Exogenous insulin infusion can decrease atherosclerosis in diabetic rodents by improving lipids, inflammation, and endothelial function. Arterioscler Thromb Vasc Biol. 2018;38(1):92-101.
