Alper Ozdemir, Hale Aral, Fusun Erdenen, Rabia Bilge Ozdemir, Omer Emecen, Guvenc Guvenen, Cuneyt Muderrisoglu

The effects of glycemic control on malondialdehyde modified low-density- lipoprotein-immunglobulin G levels in type 2 diabetics

The effects of glycemic control on malondialdehyde modified low-density-lipoprotein-immunglobulin G levels in type 2 diabetics

Objective: The aim of this study is investigation of effect of glycemic control on the levels of malondialdehyde-low-density-lipoprotein-immunglobulin G (MDA-LDL-IgG) which is supposed to be positively correlated with myocardial infarction risk in subjects with type 2 diabetes mellitus (DM).Material and Method: We evaluated the levels of glucose, triglyceride, total cholesterol, high-density-lipoprotein-cholesterol (HDL-C), low-density-lipoprotein-cholesterol (LDL-C), hemoglobin A1c (A1C) and MDA-LDL-IgG in subjects with well-controlled DM (W-DM, <7% HbA1c, n=18), poorly-controlled DM (P-DM, >7% HbA1c, n=22) and in non-diabetics (Non-DM, n=15).Results: There were no significant differences between P-DM and W-DM groups for triglyceride, total cholesterol and LDL-C levels but these tests were significantly low in the Non-DM group compared to other groups (respectively, p=0.002, p<0.001 and p=0.001). There was no significant difference between W-DM and Non-DM groups for MDA-LDL-IgG levels, but in P-DM group they were significantly higher compared to W-DM and Non-DM (p=0.002). There was a positive correlation between A1C andMDA-LDL-IgG levels (r=0.463, p= p=0.001).Conclusion: These findings suggest that the normalization of blood glucose levels in type 2 diabetics may persuade the reduced rate of the formation of new antigenic epitopes on the LDL via non-enzymatic glycosylation. The regulation of diabetes may be improved by reducing antibody formation against the MDA-LDL although there is no effect on lipid levels. A1C may not only be a good indicator of blood glucose control but also a good predictor for diabetes-related macro vascular complications.

Keywords:

Type 2 diabetes mellitus; A1C; glycemic control; Cholesterol; MDA; LDL,

PDF

___

1. Calti Gur C, Polat H, Muderrisoglu C, Altunoglu E, Yilmaz M. In Patients with Type-2 Diabetes, Diabetes Regulation, Hba1c, Duration of Diabetes, BMI, Dyslipidemia, and Microalbuminuria Compared with Macrovascular Complications. Istanbul Medical Journal. 2013 Dec 19;14(4):243–7.
2. Çeti̇nkalp DŞ. Tip 1 Diyabet ve Otoimmunite. Turkiye Klinikleri J Endocrin-Special Topics. 2010;3(2):51–8.
3. Dursunoğlu D, Evrengül H, Kaftan A, Kiliç M, Sermez Y. Koroner Ateroskleroz ve Diyabet. Turkiye Klinikleri J Cardiol. 2004;17(1):55–60.
4. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014 [Internet]. 2014. Available from: http://www.cdc.gov/diabetes/data/statistics/2014statisticsre port.html
5. Çeviker T, Sametoğlu F, Aksoy F, Özdemir AT, Aral H, Güvenen G. The Evaluation of TNF-α and CRP as Inflammatory Markers in Type 2 Diabetes-Related Complications. Istanbul Med J. 2008;9(4):58–60.
6. Gurcan Z, Polat H, Muderrisoglu C, Besler M, Ozgul RB. A Comparison of Insulin Resistance Between Hemodialysis and Peritoneal Dialysis Patients. Istanbul Medical Journal. 2011;12(2):65–8.
7. Poda M. Kalitsal Dislipdemi Fenotipleri ve Genetik İlişkiler Üzerine (Derleme). Deneysel Tip Araştirma Enstitüsü Dergisi. 2011;1(2):14–9.
8. Goldstein JL, Brown MS. History of Discovery: The LDL Receptor. Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):431–8.
9. Brown MS, Goldstein JL. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–61.
10. Parmaksiz İ. Advanced Glycation End-Products in Complications of Diabetes Mellitus. MMJ. 2011;24(3):141–8.
11. Kurban S, Mehmetoğlu İ. Okside Düşük Dansiteli Lipoprotein Otoantikorlari ve Klinik Önemi. Turkiye Klinikleri J Med Sci. 2005;25(1):73–84.
12. Binder CJ, Shaw PX, Chang M-K, Boullier A, Hartvigsen K, Hörkkö S, et al. Thematic review series: The Immune System and Atherogenesis. The role of natural antibodies in atherogenesis. J Lipid Res. 2005 Jul 1;46(7):1353–63.
13. Hansson GK, Libby P, Schönbeck U, Yan Z-Q. Innate and Adaptive Immunity in the Pathogenesis of Atherosclerosis. Circulation Research. 2002 Aug 23;91(4):281–91.
14. Andersson J, Libby P, Hansson GK. Adaptive immunity and atherosclerosis. Clinical Immunology. 2010 Ocak;134(1):33–46.
15. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837–53.
16. Lathief S, Inzucchi SE. Approach to diabetes management in patients with CVD. Trends in Cardiovascular Medicine [Internet]. [cited 2015 Nov 13];0(0). Available from: http://www.tcmonline.org/article/S1050173815001504/abst ract
17. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. New England Journal of Medicine. 2008 Oct 9;359(15):1577–89.
18. Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes. New England Journal of Medicine. 2011 Mar 3;364(9):818–28.
19. Palinski W, Rosenfeld ME, Ylä-Herttuala S, Gurtner GC, Socher SS, Butler SW, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1372–6.
20. Virella G, Lopes-Virella MF. Lipoprotein autoantibodies: measurement and significance. Clin Diagn Lab Immunol. 2003 Jul;10(4):499–505.
21. Li W, Febbraio M, Reddy SP, Yu D-Y, Yamamoto M, Silverstein RL. CD36 participates in a signaling pathway that regulates ROS formation in murine VSMCs. J Clin Invest. 2010 Nov;120(11):3996–4006.
22. Lopes-Virella MF, Baker NL, Hunt KJ, Lyons TJ, Jenkins AJ, Virella G, et al. High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes. Diabetes Care. 2012 Jun;35(6):1333–40.
23. Lopes-Virella MF, Hunt KJ, Baker NL, Moritz T, Virella G. The Levels of MDA - LDL in Circulating Immune Complexes predict Myocardial Infarction in the VADT study. Atherosclerosis. 2012 Oct;224(2):526–31.
24. Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, et al. Essentials of Glycobiology. 2009 [cited 2015 Nov 17]; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1908/
25. Bucala R, Makita Z, Koschinsky T, Cerami A, Vlassara H. Lipid advanced glycosylation: pathway for lipid oxidation in vivo. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6434–8.
26. Saad AF, Virella G, Chassereau C, Boackle RJ, LopesVirella MF. OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. J Lipid Res. 2006 Sep;47(9):1975–83.
27. Erciyas F, Taneli F, Arslan B, Uslu Y. Glycemic control, oxidative stress, and lipid profile in children with type 1 diabetes mellitus. Arch Med Res. 2004 Apr;35(2):134–40.