Long-term cardiovascular effects of insulin sensitizer troglitazone on non-diabetic individuals with insulin resistance: double blind, prospective randomized study.
OBJECTIVES
The study was undertaken to assess the long-term cardiovascular effects of troglitazone on non-diabetic individuals with insulin resistance.


BACKGROUND
It has been suggested that treatment with troglitazone or similar insulin-sensitizing agents may prevent cardiovascular complications in non-diabetic individuals with insulin resistance. However, the long-term cardiovascular effects of these agents on non-diabetic individuals remain to be defined.


METHODS
A total of 137 African-American offspring of type 2 diabetic parents, with normal glucose tolerance and insulin resistance, were randomly divided to receive troglitazone 200 mg/day (n = 40), or placebo (n = 97) for 24 months. Brachial artery blood pressure (sphygmomanometry); aortic pulse wave velocity (carotid to femoral artery, Doppler), left ventricular diameters and mass (echocardiography); ascending and abdominal aortic distensibility (echocardiography, blood pressure); and metabolic and lipid profile were assessed at baseline, 12, and 24 months after randomization (delta 12, delta 24 respectively).


RESULTS
The pulse wave velocity increased significantly in the troglitazone group compared to placebo group (p < 0.05). Changes from baseline in the troglitazone group were significant (delta 12 = 1.09 +/- 0.36 m/sec, delta 24 = 2.08 +/- 0.45 m/sec, ANOVA p < 0.001), while pulse wave velocity remained unchanged in the placebo group. This increase in pulse wave velocity is consistent with a decrease in the elastic properties of the aorta.


CONCLUSIONS
Long-term administration of troglitazone to non-diabetic African-Americans with insulin resistance was associated with a decrease in the elastic properties of the aorta. Long-term therapy with troglitazone or similar agents for the prevention of cardiovascular complications in non-diabetic individuals with insulin resistance has to be critically evaluated.