Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus

Authors: Marilia C O Sprandel, Whady A Hueb, Alexandre Segre, José A F Ramires, Roberto Kalil-Filho, Raul C Maranhão

Published in: Cardiovascular Diabetology | Issue 1/2015

Login to get access

Abstract

Background

We previously showed that unesterified-cholesterol transfer to high-density lipoprotein (HDL), a crucial step in cholesterol esterification and role in reverse cholesterol transport, was diminished in non-diabetic patients with coronary artery disease (CAD). The aim was to investigate whether, in patients with type 2 diabetes mellitus (T2DM), the occurrence of CAD was also associated with alterations in lipid transfers and other parameters of plasma lipid metabolism.

Methods

Seventy-nine T2DM with CAD and 76 T2DM without CAD, confirmed by cineangiography, paired for sex, age (40–80 years), BMI and without statin use, were studied. In vitro transfer of four lipids to HDL was performed by incubating plasma of each patient with a donor emulsion containing radioactive lipids during 1 h at 37 °C. Lipids transferred to HDL were measured after chemical precipitation of non-HDL fractions and the emulsion. Results are expressed as % of total radioactivity of each lipid in HDL.

Results

In T2DM + CAD, LDL-cholesterol and apo B were higher than in T2DM. T2DM + CAD also showed diminished transfer to HDL of unesterified cholesterol (T2DM + CAD = 7.6 ± 1.2; T2DM = 8.2 ± 1.5 %, p < 0.01) and of cholesteryl-esters (4.0 ± 0.6 vs 4.3 ± 0.7, p < 0.01). Unesterified cholesterol in the non-HDL serum fraction was higher in T2DM + CAD (0.93 ± 0.20 vs 0.85 ± 0.15, p = 0.02) and CETP concentration was diminished (2.1 ± 1.0 vs 2.5 ± 1.1, p = 0.02). Lecithin-cholesterol acyltransferase activity, HDL size and lipid composition were equal.

Conclusion

Reduction in T2DM + CAD of cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport and altogether with simultaneous increased plasma unesterified cholesterol may facilitate CAD development in T2DM.
Literature
1.
go back to reference Pasterkamp G (2013) Methods of accelerated atherosclerosis in diabetic patients. Heart 99:743–749CrossRefPubMed Pasterkamp G (2013) Methods of accelerated atherosclerosis in diabetic patients. Heart 99:743–749CrossRefPubMed
2.
go back to reference Leança CC, Nunes VS, Panzoldo NB, Zago VS, Parra ES, Cazita PM et al (2013) Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects. Cardiovasc Diabetol 12:173PubMedCentralCrossRefPubMed Leança CC, Nunes VS, Panzoldo NB, Zago VS, Parra ES, Cazita PM et al (2013) Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects. Cardiovasc Diabetol 12:173PubMedCentralCrossRefPubMed
3.
go back to reference Mooradian AD (2009) Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 5:150–159CrossRefPubMed Mooradian AD (2009) Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 5:150–159CrossRefPubMed
4.
go back to reference Fruchart JC, Davignon J, Hermans MP, Al-Rubeaan K, Amarenco P, Assmann G et al (2014) Residual macrovascular risk in 2013: what have we learned? Cardiovasc Diabetol 13:26PubMedCentralCrossRefPubMed Fruchart JC, Davignon J, Hermans MP, Al-Rubeaan K, Amarenco P, Assmann G et al (2014) Residual macrovascular risk in 2013: what have we learned? Cardiovasc Diabetol 13:26PubMedCentralCrossRefPubMed
5.
go back to reference Yassine HN, Belopolskaya A, Schall C, Stump CS, Lau SS, Reaven PD (2014) Enhanced cholesterol efflux to HDL through the ABCA1 transporter in hypertriglyceridemia of type 2 diabetes. Metabolism 63:727–734PubMedCentralCrossRefPubMed Yassine HN, Belopolskaya A, Schall C, Stump CS, Lau SS, Reaven PD (2014) Enhanced cholesterol efflux to HDL through the ABCA1 transporter in hypertriglyceridemia of type 2 diabetes. Metabolism 63:727–734PubMedCentralCrossRefPubMed
6.
go back to reference Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR (1977) High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 62:707–714CrossRefPubMed Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR (1977) High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 62:707–714CrossRefPubMed
7.
go back to reference Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD et al (1989) High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79:8–15CrossRefPubMed Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD et al (1989) High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79:8–15CrossRefPubMed
8.
go back to reference Acharjee S, Boden WE, Hartigan PM, Teo KK, Maron DJ, Sedlis SP et al (2013) Low Levels of high density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: a post hoc analysis from the COURAGE Trial. J Am Coll Cardiol 62:1826–1833CrossRefPubMed Acharjee S, Boden WE, Hartigan PM, Teo KK, Maron DJ, Sedlis SP et al (2013) Low Levels of high density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: a post hoc analysis from the COURAGE Trial. J Am Coll Cardiol 62:1826–1833CrossRefPubMed
9.
go back to reference Kontush A, Chapman MJ (2006) Functionally defective high-density lipoprotein: a newtherapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 58:342–374CrossRefPubMed Kontush A, Chapman MJ (2006) Functionally defective high-density lipoprotein: a newtherapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 58:342–374CrossRefPubMed
10.
go back to reference Rosenson RS, Brewer HB Jr, Davidson WS, Fayad ZA, Fuster V, Goldstein J et al (2012) Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125:1905–1919PubMedCentralCrossRefPubMed Rosenson RS, Brewer HB Jr, Davidson WS, Fayad ZA, Fuster V, Goldstein J et al (2012) Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125:1905–1919PubMedCentralCrossRefPubMed
12.
go back to reference Siebel AL, Natoli AK, Yap FY, Carey AL, Reddy-Luthmoodoo M, Sviridov D et al (2013) Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion. Circ Res 113:167–175CrossRefPubMed Siebel AL, Natoli AK, Yap FY, Carey AL, Reddy-Luthmoodoo M, Sviridov D et al (2013) Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion. Circ Res 113:167–175CrossRefPubMed
13.
go back to reference Abbasi A, Dallinga-Thie GM, Dullaart RP (2015) Phospholipid transfer protein activity and incident type 2 diabetes mellitus. Clin Chim Acta 439:38–41CrossRefPubMed Abbasi A, Dallinga-Thie GM, Dullaart RP (2015) Phospholipid transfer protein activity and incident type 2 diabetes mellitus. Clin Chim Acta 439:38–41CrossRefPubMed
14.
15.
go back to reference Low H, Hoang A, Forbes J, Thomas M, Lyons JG, Nestel P et al (2012) Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models. Diabetologia 55:2513–2521CrossRefPubMed Low H, Hoang A, Forbes J, Thomas M, Lyons JG, Nestel P et al (2012) Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models. Diabetologia 55:2513–2521CrossRefPubMed
16.
go back to reference Lo Prete AC, Dina CH, Azevedo CH, Puk CG, Lopes NH, Hueb WA et al (2009) In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in statin treatment. Lipids 44:917–924CrossRefPubMed Lo Prete AC, Dina CH, Azevedo CH, Puk CG, Lopes NH, Hueb WA et al (2009) In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in statin treatment. Lipids 44:917–924CrossRefPubMed
17.
go back to reference Maranhao RC, Freitas FR (2014) HDL metabolism and atheroprotection: predictive value of lipid transfers. Adv Clin Chem 65:1–41CrossRefPubMed Maranhao RC, Freitas FR (2014) HDL metabolism and atheroprotection: predictive value of lipid transfers. Adv Clin Chem 65:1–41CrossRefPubMed
18.
go back to reference Maranhao RC, Freitas FR, Strunz CM, Santos RD, Mansur AJ, Mansur AP et al (2012) Lipid transfers to HDL are predictors of precocious clinical coronary heart disease. Clin Chim Acta 413:502–505CrossRefPubMed Maranhao RC, Freitas FR, Strunz CM, Santos RD, Mansur AJ, Mansur AP et al (2012) Lipid transfers to HDL are predictors of precocious clinical coronary heart disease. Clin Chim Acta 413:502–505CrossRefPubMed
19.
go back to reference Hueb WA, Bellotti G, de Oliveira SA, Arie S, de Albuquerque CP, Jatene AD et al (1995) The Medicine, Angioplasty or Surgery Study (MASS): a prospective, randomized trial of medical therapy, balloon angioplasty or bypass surgery for single proximal left anterior descending artery stenoses. J Am Coll Cardiol 26:1600–1605CrossRefPubMed Hueb WA, Bellotti G, de Oliveira SA, Arie S, de Albuquerque CP, Jatene AD et al (1995) The Medicine, Angioplasty or Surgery Study (MASS): a prospective, randomized trial of medical therapy, balloon angioplasty or bypass surgery for single proximal left anterior descending artery stenoses. J Am Coll Cardiol 26:1600–1605CrossRefPubMed
20.
go back to reference Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed
21.
go back to reference Lima E, Maranhão RC (2004) Rapid, simple laser-light scattering method for HDL particle size in whole plasma. Clin Chem 50:1086–1091CrossRefPubMed Lima E, Maranhão RC (2004) Rapid, simple laser-light scattering method for HDL particle size in whole plasma. Clin Chem 50:1086–1091CrossRefPubMed
22.
go back to reference Bragdon JH, Eder HA, Gould RG, Havel RJ (1956) Lipid nomenclature: recommendations regarding the reporting of serum lipids and lipoproteins made by the Committee on Lipid and Lipoprotein Nomenclature of the American Society for the Study of Arteriosclerosis. Circ Res 4:129CrossRefPubMed Bragdon JH, Eder HA, Gould RG, Havel RJ (1956) Lipid nomenclature: recommendations regarding the reporting of serum lipids and lipoproteins made by the Committee on Lipid and Lipoprotein Nomenclature of the American Society for the Study of Arteriosclerosis. Circ Res 4:129CrossRefPubMed
23.
go back to reference Marotta T, Russo BF, Ferrara LA (2010) Triglyceride-to-HDL-cholesterol ratio and metabolic syndrome as contributors to cardiovascular risk in overweight patients. Obesity 18:1608–1613CrossRefPubMed Marotta T, Russo BF, Ferrara LA (2010) Triglyceride-to-HDL-cholesterol ratio and metabolic syndrome as contributors to cardiovascular risk in overweight patients. Obesity 18:1608–1613CrossRefPubMed
24.
go back to reference Hermans MP, Ahn SA, Rousseau MF (2014) Novel unbiased equations to calculate triglyceride-rich lipoprotein cholesterol from routine non-fasting lipids. Cardiovasc Diabetol 13:56PubMedCentralCrossRefPubMed Hermans MP, Ahn SA, Rousseau MF (2014) Novel unbiased equations to calculate triglyceride-rich lipoprotein cholesterol from routine non-fasting lipids. Cardiovasc Diabetol 13:56PubMedCentralCrossRefPubMed
25.
go back to reference Seviour PW, Teal TK, Richmond W, Elkeles RS (1988) Serum lipids, lipoproteins and macrovascular disease in non-insulin-dependent diabetics: a possible new approach to prevention. Diabet Med 5:166–171CrossRefPubMed Seviour PW, Teal TK, Richmond W, Elkeles RS (1988) Serum lipids, lipoproteins and macrovascular disease in non-insulin-dependent diabetics: a possible new approach to prevention. Diabet Med 5:166–171CrossRefPubMed
26.
go back to reference Kahri J, Syvanne M, Taskinen MR (1994) Plasma cholesteryl ester transfer protein activity in non-insulin-dependent diabetic patients with and without coronary artery disease. Metabolism 43:1498–1502CrossRefPubMed Kahri J, Syvanne M, Taskinen MR (1994) Plasma cholesteryl ester transfer protein activity in non-insulin-dependent diabetic patients with and without coronary artery disease. Metabolism 43:1498–1502CrossRefPubMed
27.
go back to reference Frohlich J, Dobiasova M (2003) Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography. Clin Chem 49:1873–1880CrossRefPubMed Frohlich J, Dobiasova M (2003) Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography. Clin Chem 49:1873–1880CrossRefPubMed
28.
go back to reference Ng DS (2012) The role of lecithin: cholesterol acyltransferase in the modulation of cardiometabolic risks—a clinical update and emerging insights from animal models. Biochim Biophys Acta 1821:654–659CrossRefPubMed Ng DS (2012) The role of lecithin: cholesterol acyltransferase in the modulation of cardiometabolic risks—a clinical update and emerging insights from animal models. Biochim Biophys Acta 1821:654–659CrossRefPubMed
29.
go back to reference Savel J, Lafitte M, Pucheu Y, Pradeau V, Tabarin A, Couffinhal T (2012) Very low levels of HDL cholesterol and atherosclerosis, a variable relationship—a review of LCAT deficiency. Vasc Health Risk Manag 8:357–361PubMedCentralPubMed Savel J, Lafitte M, Pucheu Y, Pradeau V, Tabarin A, Couffinhal T (2012) Very low levels of HDL cholesterol and atherosclerosis, a variable relationship—a review of LCAT deficiency. Vasc Health Risk Manag 8:357–361PubMedCentralPubMed
30.
go back to reference Rousset X, Shamburek R, Vaisman B, Amar M, Remaley AT (2011) Lecithin cholesterol acyltransferase: an anti- or pro-atherogenic factor? Curr Atheroscler Rep 13:249–256PubMedCentralCrossRefPubMed Rousset X, Shamburek R, Vaisman B, Amar M, Remaley AT (2011) Lecithin cholesterol acyltransferase: an anti- or pro-atherogenic factor? Curr Atheroscler Rep 13:249–256PubMedCentralCrossRefPubMed
31.
go back to reference Couto RD, Dallan LA, Lisboa LA, Mesquita CH, Vinagre CG, Maranhao RC (2007) Deposition of free cholesterol in the blood vessels of patients with coronary artery disease: a possible novel mechanism for atherogenesis. Lipids 42:411–418CrossRefPubMed Couto RD, Dallan LA, Lisboa LA, Mesquita CH, Vinagre CG, Maranhao RC (2007) Deposition of free cholesterol in the blood vessels of patients with coronary artery disease: a possible novel mechanism for atherogenesis. Lipids 42:411–418CrossRefPubMed
32.
go back to reference Santos RD, Hueb W, Oliveira AA, Ramires JA, Maranhao RC (2003) Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease. J Lipid Res 44:464–469CrossRefPubMed Santos RD, Hueb W, Oliveira AA, Ramires JA, Maranhao RC (2003) Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease. J Lipid Res 44:464–469CrossRefPubMed
33.
go back to reference Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K et al (2011) Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. New Eng J Med 364:127–135PubMedCentralCrossRefPubMed Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K et al (2011) Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. New Eng J Med 364:127–135PubMedCentralCrossRefPubMed
34.
go back to reference Triolo M, Kwakernaak AJ, Perton FG, de Vries R, Dallinga-Thie GM, Dullaart RP et al (2013) Low normal thyroid function enhances plasma cholesteryl ester transfer in type 2 diabetes mellitus. Atherosclerosis 228:466–471CrossRefPubMed Triolo M, Kwakernaak AJ, Perton FG, de Vries R, Dallinga-Thie GM, Dullaart RP et al (2013) Low normal thyroid function enhances plasma cholesteryl ester transfer in type 2 diabetes mellitus. Atherosclerosis 228:466–471CrossRefPubMed
35.
go back to reference Dullaart RP, de Vries R, Dallinga-Thie GM, van Tol A, Sluiter WJ (2007) Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein activity are associated with leptin in type 2 diabetes mellitus. Biochim Biophys Acta 1771:113–118CrossRefPubMed Dullaart RP, de Vries R, Dallinga-Thie GM, van Tol A, Sluiter WJ (2007) Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein activity are associated with leptin in type 2 diabetes mellitus. Biochim Biophys Acta 1771:113–118CrossRefPubMed
36.
go back to reference Inukai Y, Ito K, Hara K, Yamazaki A, Takebayashi K, Aso Y et al (2007) Serum cholesteryl ester transfer protein concentrations are associated with serum levels of total cholesterol, beta-lipoprotein and apoproteins in patients with type 2 diabetes mellitus. Med Princ Pract. 16:367–372CrossRefPubMed Inukai Y, Ito K, Hara K, Yamazaki A, Takebayashi K, Aso Y et al (2007) Serum cholesteryl ester transfer protein concentrations are associated with serum levels of total cholesterol, beta-lipoprotein and apoproteins in patients with type 2 diabetes mellitus. Med Princ Pract. 16:367–372CrossRefPubMed
37.
go back to reference Morton RE (1988) Free cholesterol is a potent regulator of lipid transfer protein function. J Biol Chem 263:12235–12241PubMed Morton RE (1988) Free cholesterol is a potent regulator of lipid transfer protein function. J Biol Chem 263:12235–12241PubMed
Metadata
Title
Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus
Authors
Marilia C O Sprandel
Whady A Hueb
Alexandre Segre
José A F Ramires
Roberto Kalil-Filho
Raul C Maranhão
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0270-8

Other articles of this Issue 1/2015

Cardiovascular Diabetology 1/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.