Influence of Etofibrate on LDL-Subtype Distribution in Patients with Diabetic Dyslipoproteinemia

Abstract

Low density lipoprotein (LDL-) particles can be subfractionated in large-buoyant (lb), intermediate-dense (id) and small-dense (sd) LDL-subtypes. Fibrates improve the LDL-subtype profile by reducing proatherogenic sd-LDL which are prominent in diabetic dyslipoproteinemia. We evaluated the effect of etofibrate on the LDL-subtype distribution in patients with type 2 diabetes mellitus (n = 13, 55 ± 18 years, BMI 27.9 ± 5.5 kg/m², HbA1c 10.1 ± 3.9 %) and diabetic dyslipoproteinemia (triglycerides 343 ± 253 mg/dl, HDL-cholesterol 36 ± 7 mg/dl, LDL-cholesterol 110 ± 37 mg/dl).

Plasma lipids (enzymatic methods) and LDL-subtypes (7 LDL-subfractions, density gradient ultracentrifugation) were measured before and during etofibrate therapy (500 mg/d, 7 - 16 weeks). Etofibrate significantly (p < 0.05, Wilcoxon-test) reduced triglycerides (- 31 ± 60 %) and increased HDL-cholesterol (+ 24 ± 22 %), whereas total cholesterol and LDL-cholesterol did not change. Cholesterol concentration decreased in sd-LDL by 12 % (p < 0.05), while it increased in id- and lb-LDL (+ 26 %,+ 39 %, respectively). Thus, the LDL-subtype profile showed a relative increase of the fraction of lb- (+ 13 ± 32 %, n.s.) and id-LDL (+ 23 ± 33 %, p < 0.05) and a relative decrease of the fraction of sd-LDL (- 19 ± 18 %, p < 0.05).

We conclude that etofibrate not only decreases triglycerides and increases HDL-cholesterol but also improves the LDL-subtype profile and thus may reduce the cardiovascular risk in patients with an abundance of sd-LDL such as diabetic patients.

Key words

Diabetes mellitus - diabetic dyslipoproteinemia - diabetic dyslipidemia - LDL-subfractions - LDL-subtypes - small dense LDL - etofibrate - fibrate

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