MODIFIED LOW-DENSITY LIPOPROT EINS IN DI ABETES MELLITUS TYPE 2

 Objective: to compare the level of modified low-density lipoproteins (mLDL) in patients with diabetes mellitus type 2 (DM2) and without DM2; to identify the factors affecting mLDL сontent.

Materials and methods. The study involved 64 patients; they were divided into 2 groups. The main group included 32 patients with DM2 (15 men and 17 women, median age – 65 years), the control group 2 included 32 patients without DM2 (15 men and 17 women, median age – 60.5 years). All patients (100 %) had arterial hypertension. Both groups were generally comparable in the main clinical and laboratory characteristics. Mann–Whitney test, Spearman correlation coefficient were used for statistical data processing.

Results. In patients with DM2 mLDL level was significantly higher (р <0.001) and correlated with blood glucose concentration (p = 0.021), glycated hemoglobin values (p <0.001) and body-weight index (p = 0.007). In patients without DM2 mLDL level correlated with bodyweight index (p <0.001). No correlation between mLDL level and standard LDL content was found in patients with DM2 and in patients without DM2 (p = 0.714 and p = 0.758 respectively).

Conclusion. DM2 is significantly associated with an increased mLDL level that is affected by parameters of carbohydrate metabolism and body-weight index. In persons without hyperlipidemia mLDL level increases in case of hyperglycemia.

1. Njajou O. T., Kanaya A. M., Holvoet P. et al. Association between oxidized LDL, obesity and type 2 diabetes in a populationbased cohort, the Health Aging and Body Composition study. Diabetes Metab Res Rev 2009;25(8):733–9. DOI: 10.1002/dmrr.1011.

2. Hulthe J., Fagerberg B. Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines (AIR Study). Arterioscler Thromb Vasc Biol 2002;22(7):1162–7.DOI: 10.1161/ 01.ATV.0000021150.63480. CD.

3. Ceriello A., Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004;24:816–23. DOI: 10.1161/01.ATV.0000122852.22604.78.

4. Holvoet P., Jenny N. S., Schreiner P. J. et al. The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007;194(1):245–52. DOI: 10.1016/j.atherosclerosis.2006.08.002.

5. Dandona P., Aljada A., Chaudhuri A. et al. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005;111:1448–54. DOI: 10.1161/01.CIR.0000158483.13093.9D.

6. Holvoet P., Kritchevsky S. B., Tracy R. P. et al. The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort. Diabetes 2004;53:1068–73. DOI: 10.2337/diabetes.53.4.1068.

7. Hoogeveen R. C., Ballantyne C. M., Bang H. et al. Circulating oxidized lowdensity lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Diabetologia 2007;50:36–42. DOI: 10.1007/s00125‑006‑0533‑8.

8. Holvoet P., Harris T. B., Tracy R. P. et al. Association of high coronary heart disease risk status with circulating oxidized LDL in the well-functioning elderly: findings from the Health, Aging, and Body Composition study. Arterioscler Thromb Vasc Biol 2003;23:1444–8. DOI: 10.1161/01.ATV.0000080379.05071.22.

9. Holvoet P., Mertens A., Verhamme P. et al. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2001;21:844–8. DOI: 10.1161/01.ATV. 21.5.844.

10. Leiva E., Wehinger S., Guzmán L., Orrego R. Role of oxidized LDL in atherosclerosis, hypercholesterolemia. Ed. Dr. Sekar Ashok Kumar. London: InTech Open, 2015. DOI: 10.5772/59375. URL: https://www.intechopen.com/books/hypercholesterolemia/role-of-oxidized-ldl-inatherosclerosis. [Accessed: 04.06.2018].

11. Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997;272(34):20963–6. DOI: 10.1074/jbc. 272.34.20963.

12. Actis Dato S. M., Rebolledo O. R. Lipoprotein glycation and glycoxidation: their importance in diabetes mellitus (In Spanish). Medicina (BAires) 2000;60(5 Pt 1):645–56.

13. Ametov A. S., Kurochkin I. O., Zubkov A. A. Diabetes mellitus and cardiovascular diseases. Russkij medicinskij zhurnal = Russian Medical Journal 2014;22(13):943–58. (In Russ.).

14. Mogilenko D. A., Kudriavtsev I. V., Trulioff A. S. et al. Modified low density lipoprotein stimulates complement C3 expression and secretion via liver X receptor and Toll-like receptor 4 activation in human macrophages. J Biol Chem 2012; 287(8):5954–68. DOI: 10.1074/jbc.M111.289322.

15. Aukrust P., Gullestad L., Lappegård K. T. et al. Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment. Circulation 2001;104(13):1494–500. DOI: 10.1161/hc3801.096353.

16. Sawamura T., Kume N., Aoyama T. et al. An endothelial receptor for oxidized lowdensity lipoprotein. Nature 1997;386(6620):73–7. DOI: 10.1038/386073a0.

17. Fujita Y., Yamaguchi S., Kakino A. et al. Lectin-like oxidized LDL receptor 1 is involved in CRP-mediated complement activation. Clin Chem 2011;57(10): 1398–405. DOI: 10.1373/ clinchem.2011.168625.

18. Obradovic M. M., Trpkovic A., Bajic V. et al. Interrelatedness between C-reactive protein and oxidized low-density lipoprotein. Clin Chem Lab Med 2015;53(1):29–34. DOI: 10.1515/cclm-2014-0590.

19. Sanda G. M., Deleanu M., Simionescu M. Sima A. V. Oxidized LDL induce C-reactive protein secretion in human macrophages through mechanisms involving oxidative stress. Annals of R. S. C. B. 2015;19(3):9–20. DOI: 10.ANN/RSCB-2015-0028: RSCB.

20. Lu J., Wang X., Wang W. et al. LOX-1 abrogation reduces cardiac hypertrophy and collagen accumulation following chronic ischemia in the mouse. Gene Ther 2012;19(5):522–31. DOI: 10.1038/gt.2011.133.

21. Zhang R., Zhang Y. Y., Huang X. R. et al. C-reactive protein promotes cardiac fibrosis and inflammation in angiotensin II-induced hypertensive cardiac disease. Hypertension 2010;55(4):953–60. DOI: 10.1161/HYPERTENSIONAHA. 109.140608.

22. Dedov I. I., Shestakova M. V., Mayorov A. Yu. et al. Standards of specialized diabetes care. Sakharniy diabet = Diabetes Mellitus 2017;20(1S):1–121. DOI: 10.14341/DM20171S8. (In Russ.).

23. Shoybonov B. B., Shoybonova B. V. Method of determination of atherogenicity of the human blood. Patent of the Russian Federation No. 2497116 from 27.10.2013. Bulletin No. 30. 10 p. URL: http://www.freepatent.ru/images/patents/494/2497116/patent-2497116.pdf. Accessed: 04.06.2018. (In Russ.).

24. Eliashevich S. O., Drapkina O. M., Shoybonov B. B. The circulating level of modified LDL and C3-convertase stabilization among patients with abdominal obesity. Problemy endokrinologii = Problems of Endocrinology 2016;62(5):44–5. DOI: 10.14341/probl201662544-45. (In Russ.).

25. Evans J. D. Straightforward Statistics for the Behavioral Sciences. Pacific Grove, СА: Brooks/Cole Pub. Co, 1996. 600 p.

26. Frostegård J., Wu R., Lemne C. et al. Circulating oxidized low-density lipoprotein is increased in hypertension. Clin Sci (Lond) 2003;105(5):615–20. DOI: 10.1042/CS20030152.

27. Liguori A., Abete P., Hayden J. M. et al. Effect of glycaemic control and age on low-density lipoprotein susceptibility to oxidation in diabetes mellitus type 1. Eur Heart J 2001;22(22):2075–84. DOI: 10.1053/euhj.2001.2655.

28. Babakr A. T., Elsheikh O. M., Almarzouki A. A. et al. Relationship between oxidized low-density lipoprotein antibodies and obesity in different glycemic situations. Diabetes Metab Syndr Obes 2014;7:513–20. DOI: 10.2147/DMSO.S70904.

29. Linton M. F., Yancey P. G., Davies S. S. et al. The role of lipids and lipoproteins in atherosclerosis. [Updated 2015 Dec 24]. In: De Groot L. J., Chrousos G., Dungan K. et al. eds. Endotext [Internet]. South Dartmouth(MA): MDText.com, Inc., 2000. URL: https://www.ncbi.nlm.nih.gov/books/NBK343489. [Accessed: 04.06.2018].