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


CONCLUSIONS
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.
Lipid Metabolism Laboratory, Heart Institute, Medical School Hospital, University of São Paulo, São Paulo, Brazil. marilia_coliveira@yahoo.com.br.
Marilia C O
MC
Sprandel
Clinical Cardiology Division, Heart Institute, Medical School Hospital, University of São Paulo, São Paulo, Brazil. whady.hueb@incor.usp.br.
Whady A
WA
Hueb
Clinical Cardiology Division, Heart Institute, Medical School Hospital, University of São Paulo, São Paulo, Brazil. alexandre.segre@incor.usp.br.
Alexandre
A
Segre
Clinical Cardiology Division, Heart Institute, Medical School Hospital, University of São Paulo, São Paulo, Brazil. jramires@incor.usp.br.
José A F
JA
Ramires
Clinical Cardiology Division, Heart Institute, Medical School Hospital, University of São Paulo, São Paulo, Brazil. roberto.kalil@incor.usp.br.
Roberto
R
Kalil-Filho
Lipid Metabolism Laboratory, Heart Institute, Medical School Hospital, University of São Paulo, São Paulo, Brazil. ramarans@usp.br.|Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. ramarans@usp.br.
Raul C
RC
Maranhão
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053299:Apolipoprotein B-100 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002788:Cholesterol Esters / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002932:Cineangiography; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D010316:Particle Size; D012307:Risk Factors
C569471:APOB protein, human; D053299:Apolipoprotein B-100; D015415:Biomarkers; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL