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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:2130-2135.)
© 1995 American Heart Association, Inc.

Articles

Abnormal Reverse Cholesterol Transport in Controlled Type II Diabetic Patients

Studies on Fasting and Postprandial LpA-I Particles

Elisabeth Cavallero; Fernando Brites; Bernard Delfly; Nathalie Nicolaïew; Christelle Decossin; Catherine De Geitere; Jean-Charles Fruchart; Regina Wikinski; Bernard Jacotot; Graciela Castro

From the Service de Médecine Interne, Nutrition, Métabolisme Lipidique (E.C., N.N., B.J.), Hôpital Henri-Mondor Créteil, France; the Department of Clinical Biochemistry (F.B., R.W.), Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; and INSERM (B.D., C.D., C. De G., J.-C.F., G.C.), Institut Pasteur de Lille, France.

Correspondence to Graciela Castro, INSERM Unité 325, Institut Pasteur, 1, rue du Professeur Calmette, Lille Cedex, France.

Abstract The high incidence and prevalence of coronary heart disease in diabetes mellitus is clearly established. The usual lipid pattern found in type II diabetic patients is a moderate increase in fasting triglyceride levels associated with low HDL cholesterol levels. These abnormalities are further amplified in the postprandial state. To study the effect of these alterations on reverse cholesterol transport, we isolated lipoprotein containing apoA-I but not apoA-II (LpA-I) particles by immunoaffinity chromatography from the plasma of well-controlled type II diabetic patients and nondiabetic matched control subjects. Different parameters involved in this antiatherogenic pathway were measured in both fasting and postprandial states. Diabetic patients had reduced levels of LpA-I particles that were protein enriched and phospholipid depleted. Gradient gel electrophoresis showed that control LpA-I particles had five distinct populations, whereas diabetic particles lacked the largest one. LpA-I isolated from diabetic plasma exhibited a decreased capacity to induce cholesterol efflux from Ob 1771 adipose cells both in fasting (15.1±10.0% versus 7.5±2.7%, P<.05) and postprandial (17.7±11.2% versus 7.7±3.9%, P<.05) states, whereas only control particles showed significantly higher ability to promote cholesterol efflux after the test meal (P=.02). Lecithin:cholesterol acyltransferase activity measured with an exogenous substrate showed a 54% increase and an 18% decrease postprandially for control subjects and patients, respectively. Thus, the different abnormalities found in the fasting state were further amplified in the postprandial situation. This resulted in LpA-I particles with aberrant size and composition and decreased ability to accomplish their antiatherogenic role in type II diabetic patients.

Key Words: type II diabetes • postprandial • LpA-I • cholesterol efflux

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