Isolde Friedrich

Clearance of postprandial lipoproteins in normolipemics: role of the apolipoprotein E phenotype.

The hepatic clearance of triglyceride-rich lipoproteins is mediated via apolipoprotein (apo) E which occurs in three common isoforms, apoE2, apoE3 and apoE4. To study the importance of the apoE isoforms on the response curves of different triglyceride-rich lipoproteins and the effect of chylomicron remnants on the composition of HDL, 37 normolipemics were investigated after a standardized fatty meal (8 apoE2/E2, 8 apoE2/E3, 8 apoE3/E3, 7 apoE3/E4 and 6 apoE4/E4). These individuals were matched for age, body mass index, fasting triglycerides, HDL-cholesterol, and apoA-I. A delayed chylomicron remnant clearance was observed only in apoE2 homozygotes, and this delay was neither correlated with fasting lip ds nor with peak lipoprotein concentrations. In apoE2/E3 heterozygotes, in contrast, the defective isoform E2 appears to be compensated for by the normal apoE isoform E3. In non-apo-E2/E2 individuals, the chylomicron remnant response was highly correlated with the magnitude of chylomicron and VLDL responses, with fasting triglycerides, and with the triglycerides enrichment and cholesterol depletion of HDL. These correlations were not observed in apoE2/E2. From these results we conclude that the chylomicron remnant response curve is an indicator of the extent of postprandial lipemia in non-apoE2/E2 individuals only.

Pioglitazone reduces atherogenic dense low density lipoprotein (LDL) particles in patients with type 2 diabetes mellitus

Aim T he new oral antidiabetic agent pioglitazone improves insulin sensitivity and glycaemic control, lowers triglycerides and increases high density lipoprotein (HDL) cholesterol in type 2 diabetes. The effect of pioglitazone on low density lipoprotein (LDL) subfractions is investigated, herein. Methods The effect of pioglitazone monotherapy (45 mg o.d. for six months) on LDL subfractions was observed in 30 patients with poorly controlled type 2 diabetes (HbA 1C > 7.5% and 150 mg/dL). The distribution of LDL subfractions was determined by equilibrium density gradient ultracentrifugation before and during treatment. Results HbA1C (9.5% before and 7.4% on treatment, p<0.001), triglycerides (-135 mg/dL [-32.2%], p=0.002) and apo B in LDL-6 (the most dense LDL subfraction) decreased significantly. The mean diameter of LDL particles increased (19.5 nm before and 19.8 nm on treatment, p=0.005), while the mean LDL density decreased significantly (from 1.0394 kg/L to 1.0381 kg/L on treatment; p=0.033). HDL increased from 36.3 mg/dL to 44.2 mg/dL (+ 21.6%, p<0.001). Total cholesterol and LDL-cholesterol did not change significantly. Conclusions The results confirm that pioglitazone improves glycaemic control in patients with type 2 diabetes. In addition, pioglitazone reduced the proportion of atherogenic dense LDL. The effects of pioglitazone on lipoprotein metabolism may translate into a reduced risk for atherosclerotic complications in type 2 diabetes.