Abnormal distribution of VLDL subfractions in Type 1 (insulin-dependent) diabetic patients: could plasma lipase activities play a role?

Summary Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit S_f]>400, B: S_f, 175–400, C: S_f 100–175, D: S_f 20–100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbA_1c 6.9±0.5%) (mean±SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values. Compared to control subjects, diabetic patients showed a reduced total lipid concentration of VLDL of intermediate size (B and C) reaching statistical significance only for VLDL C (0.16±0.02 vs 0.24±0.03 mmol/l; p <0.05). Expressing each VLDL subfraction as percent of the total VLDL lipid concentration, a significant decrease in particles of intermediate size (C) (20.5±1.6 vs 27.9±1.5%; p <0.005) was present, which was compensated by an increase in the smallest ones (D) (50.5±2.7 vs 37.4±3.1%; p <0.05). VLDL of smaller size were also the only particles with an abnormal composition consisting of a significant increase in esterified cholesterol (12.2±0.8 vs 8.7±1.2%, p <0.01). Post-heparin hepatic lipase activity was significantly reduced in diabetic patients as compared to control subjects (232.9±27.9 vs 332±42.3 mU/ml; p <0.05) while post-heparin lipoprotein lipase activity was similar in the two groups. Furthermore, hepatic lipase activity was inversely related to the percentage of smaller VLDL (D)(r=–0.72; p <0.01) in diabetic patients and this relationship was independent of changes in intermediate VLDL (VLDL C). In conclusion the data suggest that Type 1 diabetic patients, although normolipidaemic and in good blood glucose control, show a shift in the distribution of VLDL subclasses toward VLDL of a smaller size which also have an abnormal composition. The different distribution of VLDL subfractions seems to be related to a reduced hepatic lipase activity.