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

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Abstract
Aim The 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 (HbA1C ≥ 7.5% and < 11.5% and triglycerides ≥ 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.

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