Troglitazone Decreases the Proportion of Small, Dense LDL and Increases the Resistance of LDL to Oxidation in Obese Subjects

Cees JJ Tack; Paul Smits; Pierre NM Demacker; Anton FH Stalenhoef

doi:10.2337/diacare.21.5.796

Original Articles

Troglitazone Decreases the Proportion of Small, Dense LDL and Increases the Resistance of LDL to Oxidation in Obese Subjects

Cees JJ Tack, MD,
Paul Smits, MD,
Pierre NM Demacker, PHD and
Anton FH Stalenhoef, MD

Department of Internal Medicine, University Hospital Nijmegen Nijmegen, The Netherlands
Division of General Internal Medicine, and the Department of Pharmacology, University Hospital Nijmegen Nijmegen, The Netherlands

Address correspondence and reprint requests to Anton F.H. Stalenhoef, MD, Division of General Internal Medicine 541, Department of Medicine, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Diabetes Care 1998 May; 21(5): 796-799. https://doi.org/10.2337/diacare.21.5.796

Abstract

OBJECTIVE Insulin resistance is associated with a predominance of small, atherogenic LDL particles that are more prone to oxidative modification. Treatment with the insulin-sensitizer troglitazone may improve LDL composition and resistance to oxidation.

RESEARCH DESIGN AND METHODS In a randomized double-blind crossover design, 15 obese subjects were treated with either 400 mg troglitazone daily or placebo for 8 weeks. Insulin sensitivity (clamp), (apo)lipoproteins, LDL subclass pattern, plasma TBARS, and ex vivo LDL oxidation were determined.

RESULTS Troglitazone treatment improved insulin sensitivity. LDL cholesterol increased from 2.58 ± 0.18 to 2.77 ± 0.20 mmol/1 (P = 0.03) because of an increase in large (buoyant) LDL₁ (from 0.45 ± 0.04 to 0.62 ± 0.09 mmol/1, P = 0.008). Because small (dense) LDL₃ decreased, LDL₁:LDL₃ ratio increased (P = 0.02). Plasma TBARS concentration declined significantly, and the lag time of ex vivo LDL oxidation showed a small but significant increase.

CONCLUSIONS In obese subjects, treatment with troglitazone improves insulin sensitivity, increases the ratio of large buoyant to small dense LDL, and appears to enhance the resistance of the LDL particle to oxidation. These qualitative changes in lipoproteins may have a beneficial effect on cardiovascular risk profile and compensate for a small increase in LDL cholesterol.