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

  1. Anton FH Stalenhoef, MD
  1. Department of Internal Medicine, University Hospital Nijmegen Nijmegen, The Netherlands
  2. Division of General Internal Medicine, and the Department of Pharmacology, University Hospital Nijmegen Nijmegen, The Netherlands
  1. 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.


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.

  • Received August 6, 1997.
  • Revision received January 15, 1998.
  • Accepted January 15, 1998.
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