Accessibility of human apolipoprotein B-100 epitopes in insulin-dependent diabetes: relation with the surface lipid environment of atherogenic particles.

The physicochemical modifications (composition and conformation) of lipoproteins containing apolipoprotein B-100 (apo B-100) were studied in normocholesterolaemic adequately controlled Type 1 insulin-dependent diabetic patients. Thirty-one normocholesterolaemic (serum cholesterol < 6.50 mmol/l) diabetic male patients and 31 age-and body mass index-adjusted healthy normolipaemic male controls were studied. Cholesterol and choline-containing phospholipids were measured in total serum and in two lipoprotein subfractions containing or not apo B (LpB and LpnoB respectively). These subfractions were separated by precipitation with concanavalin A. Total apo B-100 and two lipoprotein particles defined according to their apo B-100 epitope accessibility were determined using respectively anti-apo B polyclonal and two monoclonal antibodies that reacted with specific epitopes on the apo B molecule. Despite a classical lipid profile (cholesterol and triglyceride levels), which was quite normal in plasma from patients as compared to controls, a depletion of choline-containing phospholipid content in serum and more specifically in LpB particles was observed in diabetic patients. Decreased cholesterol content was also observed in LpB particles. Immunological analysis demonstrated an increased number of lipoprotein particles (a condition previously related to coronary artery disease) and decreased immunoaccessibility of a conformationally expressed apo B-100 epitope. These conformational changes were correlated with modifications of the surface phospholipid environment of LpB particles. It is concluded that subtle abnormalities in the composition and conformation of atherogenic apo-B-containing lipoproteins occur in Type 1 diabetes mellitus. These structural modifications may be one factor accounting for the increased rate of atherosclerosis in diabetes, despite the existence of a normal classical lipid profile.