INSULIN-INDUCED VASODILATATION AND ENDOTHELIAL FUNCTION IN OBESITY INSULIN RESISTANCE - EFFECTS OF TROGLITAZONE/

Insulin resistance is associated with a decreased vasodilator response to insulin. Because insulin's vasodilator effect is nitric oxide depe ndent, this impairment may reflect endothelial dysfunction. Troglitazo ne, an insulin-sensitiser, might thus improve insulin-dependent and/or endothelium-dependent vascular function in insulin resistant obese su bjects. For 8 weeks, fifteen obese subjects were treated with either 4 00 mg troglitazone once daily or placebo, in a randomised, double-blin d, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses (plethysmography) to intra-arterial adm inistered acetylcholine and sodium nitroprusside; insulin sensitivity and insulin-induced vascular and neurohumoral responses (clamp); vasoc onstrictor responses to N-G-monomethyl-L-arginine (L-NMMA) during hype rinsulinaemia; and ambulatory 24-h blood pressure (ABPM). Baseline dat a (placebo) of obese subjects were compared with those obtained in lea n control subjects. Obese subjects were insulin resistant compared wit h leans (whole-body glucose uptake: 26.8 +/- 3.0 vs. 53.9 +/- 4.3 mu m ol.kg(-1).min(-1), p < 0.001). Troglitazone improved whole-body glucos e uptake (to 31.9 +/- 3.3 mu mol.kg(-1).min(-1), p = 0.028), and forea rm glucose uptake (from 1.09 +/- 0.54 to 2.31 +/- 0.69 mu mol.dL(-1).m in(-1), p = 0.006). Insulin-induced vasodilatation was blunted in obes e subjects (percent increase in forearm blood flow (FBF) in lean 66.5 +/- 23.0%, vs. 10.1 +/- 11.3 % in obese, p = 0.04), but did not improv e during troglitazone. Vascular responses to acetylcholine, sodium nit roprusside and L-NMMA did not differ between the obese and lean group, nor between both treatment periods in the obese individuals. In concl usion, in insulin resistant obese subjects, endothelial vascular funct ion is normal despite impaired vasodilator responses to insulin. Trogl itazone improved insulin sensitivity but it had no effects on endothel ium-dependent and-independent vascular responses. These data do not su pport an association between insulin resistance and endothelial functi on.