RESUMEN
Fibrates, activators of the nuclear receptor PPARalpha, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPARalpha activation improves insulin resistance and vascular function, we determined the effects of fenofibrate in healthy adults with insulin resistance induced by short-term glucocorticoid administration. Eighteen normal-weight subjects were studied in four stages: at baseline, after 21 days of fenofibrate (160 mg/day) alone, after 3 days of dexamethasone (8 mg/day) added to fenofibrate, and after 3 days of dexamethasone added to placebo (dexamethasone alone). Dexamethasone alone caused hyperinsulinemia, increased glucose, decreased glucose disposal, and reduced insulin-induced suppression of hepatic glucose production as determined by hyperinsulinemic euglycemic clamp and increased systolic blood pressure as determined by ambulatory monitoring, features associated with an insulin-resistant state. Fenofibrate improved fasting LDL and total cholesterol in the setting of dexamethasone treatment but had no significant effect on levels of insulin or glucose, insulin-stimulated glucose disposal, or insulin suppression of glucose production during clamps, or ambulatory monitored blood pressure. In the absence of dexamethasone, fenofibrate lowered fasting triglycerides and cholesterol but unexpectedly increased systolic blood pressure by ambulatory monitoring. These data suggest that PPARalpha activation in humans does not correct insulin resistance induced by glucocorticoids and may adversely affect blood pressure.
Asunto(s)
Presión Sanguínea/fisiología , Glucocorticoides/farmacología , Resistencia a la Insulina/fisiología , PPAR alfa/metabolismo , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Dexametasona/farmacología , Femenino , Fenofibrato/farmacología , Antebrazo/irrigación sanguínea , Técnica de Clampeo de la Glucosa , Humanos , Hipolipemiantes/farmacología , Masculino , Flujo Sanguíneo Regional/fisiologíaRESUMEN
This study tested the hypothesis that the mitral valve E point-to-septal separation (EPSS) can be used to quantify the left ventricular (LV) ejection fraction (EF) on a continuous scale rather than simply as "normal" or "reduced." After excluding 5 patients with mitral valve prostheses, asymmetric septal hypertrophy, or significant aortic insufficiency, EPSS was measured in 42 patients by 3 independent observers on a cardiac magnetic resonance image identical to the echocardiographic parasternal long-axis view. In each patient, the reference standard LVEF was calculated from the magnetic resonance short-axis cross-sectional stack images by Simpson's rule and ranged from 11% to 72%. For all 42 patients, linear regression revealed the relation magnetic resonance imaging (MRI) LVEF = 75.5 - 2.5. EPSS (millimeters). Correlation between EPSS and the MRI LVEF for the 3 observers agreed closely, ranging from r = 0.78 to r = 0.82 (SEE 9 to 10), with similar regression coefficients. After blinded segmental wall motion scoring of the gated magnetic resonance cine images of the left ventricle in each patient, correlations, SEEs, and regression coefficients were found to be very similar in the 21 patients with the most homogenous wall motion, compared with the 21 patients with the most heterogenous wall motion. In conclusion, clinically useful quantitative prediction of the LVEF as a continuous variable can be obtained from the EPSS with a simple linear regression equation in a substantial portion of patients and may be a useful adjunct for assessment of LV function.