Yeni Tanı Almış Tip 2 Diabetes Mellitus Hastalarında Plazma E Vitamini ve Plazma Nitrit/Nitrat Anyon Düzeylerinin Değerlendirilmesi

Abstract

Amaç: Oksidatif stres, tip 2 Diabetes mellitus (T2DM) başlangıcını indükler. Hem plazma E vitamini (EV) hem de nitrit/nitrat anyon (NOx) seviyeleri, farklı mekanizmalar yoluyla diyabetin neden olduğu endotelyal hasarı belirlemek için çok önemli faktörler olabilir. Bu nedenle bu çalışmada yeni tanı almış T2DM hastalarının plazma EV ve NOx konsantrasyonlarını değerlendirmeyi ve hastaların lipid profilleri ile herhangi bir korelasyon olup olmadığını anlamayı amaçladık. Gereç ve Yöntemler: Hastalar (n=15) ve kontroller (n=15) üniversitemiz diyabet polikliniğine sağlık muayenesi için ilk geldiklerinde kan örnekleri alındı ve plazma EV ve NOx düzeylerinin saptanması için kullanıldı. Hasta dosyaları hem demografik verileri hem de biyokimyasal parametreleri kaydetmek için değerlendirildi. Veriler Kolmogorov-Smirnov testine göre normal dağıldı. Bu nedenle hasta ve kontrol verilerinin karşılaştırılmasında Student t testi ve korelasyon analizi için Pearson testi uygulandı. Bulgular: Yeni tanı konmuş T2DM hastalarında total kolesterol (TK) ve trigliserit düzeyleri anlamlı olarak yükselirken (sırasıyla p=0,036 ve p<0,001), HDL-kolesterol düzeyleri ise anlamlı düzeyde azaldı (p<0,001). T2DM hastalarında plazma NOx seviyelerindeki artış TK seviyeleri ile pozitif korelasyon gösterdi (r=0,392, p=0,032). Diyabet grubunda plazma EV seviyeleri azaldı. Plazma EV ve TK (r=-0,415, p=0,022) ve ayrıca trigliserit (r=-0,380, p=0,039) düzeyleri arasında anlamlı bir negatif korelasyon bulundu. Sonuç: Bu çalışma, EV'nin hücre zarı üzerindeki koruyucu etkisinin T2DM'de azaldığını göstermektedir. Plazma NOx seviyelerinin yükselmesi, hiperglisemide artan nitrik oksit sentaz seviyelerine bağlıdır. Plazma EV ve NOx seviyeleri arasında bir ilişki bulunmamakla birlikte, özellikle yüksek TK seviyeleri olan hastalarda T2DM'nin neden olduğu vasküler hasarı anlamada spesifik biyobelirteçler olarak kullanılabilirler.

Keywords

• E vitamini
• nitritler
• nitratlar
• kolesterol
• diabetes mellitus;tip 2

Project Number

BAP 2015-92436924-01

The Evaluation of Plasma Vitamin E and Plasma Nitrite/Nitrate Anion Levels in Newly Diagnosed Type 2 Diabetes Mellitus Patients

Abstract

Aim: Oxidative stress induces the onset of type 2 Diabetes mellitus (T2DM). Both plasma vitamin E (VE) and nitrite/nitrate anion (NOx) levels might be crucial factors to determine diabetes induced endothelial damage through different mechanisms. Therefore, in this study, we aimed to evaluate plasma VE and NOx concentrations of newly diagnosed T2DM patients and to understand whether any correlation exists with the patients’ lipid profiles. Material and Methods: Blood samples were taken when the patients (n=15) and the controls (n=15) first came to our university’s diabetes policlinic for investigation and were used to detect plasma VE and NOx levels. Patients’ files were evaluated to record both the demographic data and biochemical parameters. The data was distributed normally according to Kolmogorov-Smirnov test. Therefore, Student t test was chosen to compare patient and control data and Pearson test was applied for correlation analysis. Results: In newly diagnosed T2DM patients, total cholesterol (TC) and triglyceride levels were found to be significantly elevated (p=0.036, and p<0.001, respectively), whereas, HDL-cholesterol levels were significantly reduced (p<0.001). Plasma NOx levels increased in T2DM patients and this was in positive correlation with TC levels (r=0.392, p=0.032). Plasma VE levels reduced in the diabetic group. A significant negative correlation was found between plasma VE and TC (r=-0.415, p=0.022) as well as triglyceride (r=- 0.380, p=0.039) levels. Conclusion: This study demonstrates that the protective effect of VE on cell membrane decreases in T2DM. The elevation of plasma NOx levels is due to increased nitric oxide synthase levels in hyperglycemia. Although no correlation was found between plasma VE and NOx levels, they can be used as specific biomarkers in understanding T2DM induced vascular damage especially in patients with high TC levels.

Keywords

• vitamin E
• nitrites
• nitrates
• cholesterol
• diabetes mellitus;type 2

Supporting Institution

Zonguldak Bulent Ecevit University Scientific Research Project (BAP) Unit

Project Number

BAP 2015-92436924-01

Thanks

We would like to thank Cinar Severcan (PhD) for his help in statistical analysis.

References

1. [1]. Q. Jiang. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy, Free Radic. Biol. Med. 2014;72:76–90. https://doi.org/10.1016/j.freeradbiomed.2014.03.035.
2. [2]. J. Ishwarlal, A. William, K. Manpreet. Management of hypertriglyceridemia in the diabetic patient, Curr Diab Rep. 2010;10:316–320. https://doi.org/10.1007/s11892-010-0124-4.
3. [3]. K. Ogurtsova, J.D. da Rocha Fernandes, Y. Huang, U. Linnenkamp, L. Guariguata, N.H. Cho, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040, Diabetes Res Clin Pract. 2017;128:40-50. https://doi.org/10.1016/j.diabres.2017.03.024.
4. [4]. M. Bueno, J. Wang, A.L. Mora, M.T. Gladwin. Nitrite signaling in pulmonary hypertension: mechanisms of bioactivation, signaling, and therapeutics. Antioxid Redox Signal. 2013;18:1797-809. https://doi.org/ 10.1089/ars.2012.4833.
5. [5]. H.A. Hadi, J.A. Suwaidi. Endothelial dysfunction in diabetes mellitus, Vasc Health Risk Manag. 2007;3:853–876.
6. [6]. P. Vallance, N. Chan. Endothelial function and nitric oxide: clinical relevance, Heart. 2001; 85:342-50. https://doi.org/10.1136/heart.85.3.342.
7. [7]. American Diabetes Association. 1. Improving care and promoting health in populations: Standards of Medical Care in Diabetes—2021, Diabetes Care. 2021;44(Suppl.1):S7–S14. https://doi.org/10.2337/dc21-S001.
8. [8]. R.G. Martinek. Method for the determination of vitamin E (total tocopherols) in serum, Clin Chem. 1964; 10: 1078-1086. https://doi.org/10.1093/clinchem/10.12.1078.

9. [9]. L.C. Green, D.A. Wagner, J. Glogowski, P.L. Skipper, J.S. Wishnok, S.R. Tannenbaum. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids, Anal Biochem. 1982;126:131-138. https://doi.org/10.1016/0003-2697(82)90118-x.
10. [10]. D. Giustarini, R. Rossi, A. Milzani, I. Dalle-Donne. Nitrite and nitrate measurement by Griess reagent in human plasma: evaluation of interferences and standardization, Methods Enzymol. 2008; 440:361-80. https://doi.org/ 10.1016/ S0076-6879(07)00823-3.
11. [11]. R.B. D'Agostino, R.F. Hamman, A.J. Karter, L. Mykkanen, L.E. Wagenknecht, S.M. Haffner. Cardiovascular disease risk factors predict the development of type 2 diabetes: the insulin resistance atherosclerosis study, Diabetes Care. 2004; 27:2234–2240.
12. [12]. R. Xingxing, C. Zeng Ai, Z. Shuang, H. Tingting, L. Yangxue, L. Wei, et al. Association between triglyceride to HDL-C ratio (TG/HDL-C) and insulin resistance in chinese patients with newly diagnosed type 2 diabetes mellitus. PLoS One. 2016;11(4):e0154345. https://doi.org/10.1371/journal.pone.0154345.
13. [13]. S. Safari, M. Amini, A. Aminorroaya, A. Feizi. Patterns of changes in serum lipid profiles in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients, Lipids Health Dis. 2020; 19;193. https://doi.org/ 10.1186/s12944-020-01371-y.
14. [14]. I.J. Goldberg. Diabetic dyslipidemia: causes and consequences, The Journal of Clinical Endocrinology & Metabolism. 2001; 86:965–971. https://doi.org/ 10.1210/jcem.86.3.7304.
15. [15]. K. Maejima, S. Nakano, M. Himeno, S. Tsuda, H. Makiishi, T. Ito, et al. Increased basal levels of plasma nitric oxide in Type 2 diabetic subjects. Relationship to microvascular complications, J Diabetes Complications. 2001; 15:135-43. https://doi.org/10.1016/s1056-8727 (01)00144-1.
16. [16]. F. Cosentino, K. Hishikawa, Z.S. Katusic, T.F. LuÈsher. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells, Circulation. 1997; 96:25-28. https://doi.org/10.1161/01.cir.96.1.25.
17. [17]. R. Zhang, X.J. Wang, H.D. Zhang, X.Q. Sun, QH Zhao, L. Wang, et al. Profiling nitric oxide metabolites in patients with idiopathic pulmonary arterial hypertension, Eur Respir J. 2016;48:1386–1395. https://doi.org/10.1183/13993003.00245-2016.
18. [18]. S. Tanaka, A. Yashiro, Y. Nakashima, H. Nanri, M. Ikeda, A. Kuroiwa. Plasma nitrite/nitrate level is inversely correlated with plasma low-density lipoprotein cholesterol level, Clin Cardiol. 1997; 20:361-5. https://doi.org/10.1002/clc.4960200412.
19. [19]. J.T. Salonen, K. Nyyssonen, T.P. Tuomainen, P.H. Maenpaa, H. Korpela, G.A. Kaplan, et al. Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men, BMJ, 1995;311:1124-1127. https://doi.org/10.1136/bmj.311.7013.1124.
20. [20]. Nourooz-Zadeh, A. Rahimi, J. Tajaddini-Sarmadi, H. Tritschler, P. Rosen, B. Halliwell, D.J. Betteridge. Relationships between plasma measures of oxidative stress and metabolic control in NIDDM, Diabetologia,1997;40:647-653. https://doi.org/10.1007/s001250050729.
21. [21]. P. Martin-Gallan, A. Carrascosa, M. Gussinye, C. Dominguez. Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications, Free Radic. Biol. Med., 2003; 34:1563-1574. https://doi.org/10.1016/s0891-5849 (03) 00185-0.
22. [22]. J. Arnlov, B. Zethelius, U. Riserus, S. Basu, C. Berne, B. Vessby, et al. Serum and dietary beta-carotene and alpha-tocopherol and incidence of type 2 diabetes mellitus in a community-based study of Swedish men: report from the Uppsala Longitudinal Study of Adult Men (ULSAM) study, Diabetologia, 2009;52:97-105. https://doi.org/10.1007/s00125-008-1189-3.
23. [23]. E.J. Mayer-Davis, T. Costacou, I. King, D.J. Zaccaro, R.A. Bell. Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: the Insulin Resistance and Atherosclerosis Study (IRAS), Diabetes Care, 2002; 25:2172-2177. https://doi.org/10.2337/diacare.25.12.2172.
24. [24]. S. Liu, I.M. Lee, Y. Song, M. Van Denburgh, N.R. Cook, J.E. Manson, et al. Vitamin E and risk of type 2 diabetes in the women's health study randomized controlled trial, Diabetes. 2006; 55:2856-2862. https://doi.org/10.2337/db06-0456.
25. [25]. M. Rafraf, B. Bazyun, M.A. Sarabchian, A. Safaeiyan, P. Gargari. Vitamin E improves serum Paraoxonase-1 activity and some metabolic factors in patients with type 2 diabetes: no effects on nitrite/nitrate levels, Journal of the American College of Nutrition. 2016; 35:521-528. https://doi.org/10.1080/07315724.2015.1116896.
26. [26]. W. Engelen, B.M. Keenoy, J. Vertommen, I. De Leeuw. Effects of long-term supplementation with moderate pharmacologic doses of vitamin E are saturable and reversible in patients with type 1 diabetes. Am. J. Clin. Nutr. 2000; 72:1142-1149. https://doi.org/10.1093/ajcn/72.5.1142.