Zehra SERDAR, Emre SARANDÖL, Sürmen Esma GÜR, Melahat DİRİCAN

Lecithin: Cholesterol acyltransferase activity and cholesteryl ester transfer rate in patients with diabetes mellitus

Several factors may be responsible for the high prevalence of atherosclerosis in diabetes mellitus, including alterations in reverse cholesterol transport. In the present study, the activity of plasma lecithin:cholesterol acyltransferase (LCAT) and the cholesteryl ester transfer rate, and concentrations of lipids and lipoproteins were measured in 11 patients with insulin-dependent diabetes mellitus (type 1), 42 patients with noninsulin-dependent diabetes mellitus (type 2) and compared with those in age-matched control groups (Control I, n = 14; and Control II, n = 29, respectively). No statistically significant differences were observed in plasma total cholesterol, triglyceride, ester cholesterol or very low density lipoprotein (VLDL)-cholesterol concentrations between the diabetic and control groups. High density lipoprotein (HDL)- and HDL2-cholesterol levels were significantly lower in the diabetic patients. Plasma free cholesterol and low density lipoprotein (LDL)-cholesterol concentrations were higher in the type 2 diabetics than in the control subjects. LCAT activity was significantly lower in both groups of diabetic patients than in the control groups. The mass of cholesteryl ester transferred from HDL to VLDL + LDL was significantly greater in the diabetic groups than in the controls. In conclusion, the decrease in LCAT activity and the increase in cholesteryl ester transfer observed with both type 1 and type 2 diabetics could affect the reverse cholesterol transport of HDL and contribute to the development of atherosclerosis in diabetes.

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1. Bierman EL. George Lyman Duff Memorial Lecture: Atherogenesis in diabetes. Arterioscler Thromb 12: 647- 656, 1992. 2. Tall AR. Plasma cholesteryl ester transfer protein. J Lipid Res 34: 1255- 1274, 1993. 3. Kwiterovich PO. The antiatherogenic role of high-density lipoprotein cholesterol. Am J Cardiol 82: 13Q-21Q, 1998.
4. Franceschini G, Maderna P, Sirtori CR. Reverse cholesterol transport: physiology and pharmacology. Atherosclerosis 88: 99-107, 1991. 5. Jonas A. Lecithin-cholesterol acyltransferase in the metabolism of high-density lipoproteins. Biochim Biophys Acta 1084: 205-220, 1991. 6. Fielding CJ, Reaven GM, Liu G, Fielding PE. Increased free cholesterol in plasma low and very low density lipoproteins in non-insulin dependent diabetes mellitus: its role in the inhibition of cholesteryl ester transfer. Proc Natl Acad Sci USA 81: 2512-2516, 1984. 7. Yamashita S, Hirano K, Sakai N, Matsuzawa Y. Molecular biology and pathophysiological aspects of plasma cholesteryl ester transfer protein. Biochim Biophys Acta 1529: 257-275, 2000. 8. Goldstein JL, Ho YK, Brown MS, Innerarity TL, Mahley RW. Cholesteryl ester accumulation in macrophages resulting from receptor-mediated uptake and degradation of hypercholesterolemic canine beta-very low density lipoproteins. J Biol Chem 255: 1839-1848, 1980. 9. Andreoli TE, Carpenter CCJ, Bennett JC, Plum F. Cecil Essentials of Medicine eviri Editr: Tuzcu M. evik MatbaasÝ, 4th Ed, 2000, pp: 533-546 10. Warnick GR, Benderson J, Albers JJ. Dextran sulfate-Mg2 + precipitation procedure for quantitation of highdensity lipoprotein cholesterol. Clin Chem 28: 1379-1388, 1982. 11. Olmos JM, Lasuncion MA, Herrera E. Dextran sulfate complexes with potassium phosphate to interfere in determinations of high-density lipoprotein cholesterol. Clin Chem 38: 233-237, 1992. 12. Kerscher L, Schiefer S, Draeger B, Maier J, Ziegenhorn J. Precipitation methods for the determination of LDLcholesterol. Clin Biochem 18: 118-125, 1985. 13. Hitz J, Steinmetz J, Siest G. Plasma lecithin: cholesterol acyltransferaseÐ reference values and effects in xenobiotics. Clin Chim Acta 133: 85- 96, 1983. 14. Bagdade JD, Ritter MC, Subbaiah PV. Accelerated cholesteryl ester transfer in patients with insulin-dependent diabetes mellitus. Eur J Clin Invest 21: 161-167, 1991. 15. Bagdade JD, Lane JT, Subbaiah PV, Otto ME, Ritter MC. Accelerated cholesteryl ester transfer in noninsulindependent diabetes mellitus. Atherosclerosis 104: 69-77, 1993. 16. Mann CJ, Yen FT, Grant AM, Bihain BE. Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia. J Clin Invest 88: 2059-2066, 1991. 17. Tall A, Granot E, Brocia R, Hesler C, Williams K, Denke M. Accelerated transfer of cholesteryl esters in dyslipidemic plasma. Role of cholesteryl ester transfer protein. J Clin Invest 79: 1217-1225, 1987. 18. Bagdade JD, Ritter MC, Subbaiah PV. Accelerated cholesteryl ester transfer in plasma of patients with hypercholesterolemia. J Clin Invest 87: 1259-1265, 1991. 19. Fielding PE, Fielding CJ, Havel RJ, Kane JP, Tun P. Cholesterol net transport, esterification, and transfer in human hyperlipidemic plasma. J Clin Invest 71: 449-460, 1983. 20. Medina WL, Nunes VS, Carrilho AJ et al. High-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins mediated by cholesteryl ester transfer protein in the fasting and postprandial periods are not altered in type 1 diabetes mellitus. Eur J Intern Med 11: 264-270, 2000. 21. Sutherland WH, Walker RJ, Lewis- Barned NJ, Pratt H, Tillman HC. Plasma cholesteryl ester transfer in patients with non-insulin dependent diabetes mellitus. Clin Chim Acta 231: 29-38, 1994. 22. Elchebly M, Porokhov B, Pulcini T, Berthezene F, Ponsin G. Alterations in composition and concentration of lipoproteins and elevated cholesteryl ester transfer in non-insulin-dependent diabetes mellitus (NIDDM). Atherosclerosis 123: 93-101, 1996. 23. Ritter MC, Bagdade JD. Contribution of glycaemic control, endogenous lipoproteins and cholestryl ester transfer protein to accelerated cholestryl ester transfer in IDDM. Eur J Clin Invest 24: 607-614, 1994. 24. Ritter MC, Bagdade JD. Changes in high density lipoprotein subfraction lipids during neutral lipid transfer in healthy subjects and in patients with insulindependent diabetes mellitus. Lipids 31: 1-7, 1996. 25. Colhoun HM, Scheek LM, Rubens MB et al. Lipid transfer protein activities in type 1 diabetic patients without renal failure and nondiabetic control subjects and their association with coronary artery calcification. Diabetes 50(3): 652-659, 2001. 26. Morton RE. Free cholesterol is a potent regulator of lipid transfer protein function. J Biol Chem 263: 12235- 12241, 1988. 27. Dullaart RP, Groener JE, Erkelens DW. Effect of the composition of very low and low density lipoproteins in man, on the rate of cholesteryl ester transfer from high density lipoproteins, studied in vitro. Eur J Clin Invest 17: 241-248, 1987. 28. Bagdade JD, Buchanan WE, Kuusi T, Taskinen MR. Persistent abnormalities in lipoprotein composition in noninsulin-dependent diabetes after intensive insulin therapy. Arteriosclerosis 10: 232-239, 1990. 29. Lottenberg SA, Lottenberg AM, Nunes VS, McPherson R, Quintao EC. Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in type II diabetics and normal controls. Atherosclerosis 127: 81-90, 1996. 30. Sammett D, Tall AR. Mechanisms of enhancement of cholesteryl ester transfer protein activity by lipolysis. J Biol Chem 260: 6687-6697, 1985.