Troglitazone decreases the proportion of small, dense LDL and increases the resistance of LDL to oxidation in obese subjects.
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.


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/l (P = 0.03) because of an increase in large (buoyant) LDL1 (from 0.45 +/- 0.04 to 0.62 +/- 0.09 mmol/l, 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.
Tack
C J
CJ
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Smits
P
P
Demacker
P N
PN
Stalenhoef
A F
AF
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D008078:Cholesterol, LDL / Q000737:chemistry / Q000187:drug effects*; D002839:Chromans / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D010084:Oxidation-Reduction / Q000187:drug effects; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D008078:Cholesterol, LDL; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone; D005947:Glucose