The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in XXXX with @entity2012 .

@entity1 @entity844 @entity2365 @entity442 @entity2012 @entity99 @entity413
CONTEXT: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum @entity442 concentrations in most @entity1 with @entity2012 . The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described. @entity1 AND METHODS: We assessed basal and insulin-stimulated (euglycemic clamp) substrate metabolism in seven @entity1 with active @entity2012 before and after 4-wk pegvisomant treatment (15 mg/d) in an open design. RESULTS: After pegvisomant, @entity442 decreased, whereas GH increased ( @entity442 , 621 +/- 82 vs. 247 +/- 33 microg/liter, P = 0.02; GH, 5.3 +/- 1.5 vs. 10.8 +/- 3.3 microg/liter, P = 0.02). Basal serum insulin and plasma @entity413 levels decreased after treatment (insulin, 54 +/- 5.9 vs. 42 +/- 5.3 pmol/liter, P = 0.001; @entity413 , 5.7 +/- 0.1 vs. 5.3 +/- 0.0 mmol/liter, not significant), whereas @entity2365 kinetics were unaltered. During the clamp, the @entity413 infusion rate increased after pegvisomant (3.1 +/- 0.5 vs. 4.4 +/- 0.6 mg/kg.min, P = 0.02), whereas the suppression of endogenous @entity413 production tended to increase (0.7 +/- 0.0 vs. 0.5 +/- 0.1 mg/kg.min, not significant). Total resting energy expenditure decreased after pegvisomant treatment (1703 +/- 109 vs. 1563 +/- 101 kcal/24 h, P = 0.03), but the rate of lipid oxidation did not change significantly. CONCLUSIONS: 1) Pegvisomant treatment for 4 wk improves peripheral and @entity99 in @entity2012 . 2) This is associated with a decrease in resting energy expenditure, whereas free @entity844 metabolism is unaltered. 3) The data support the important direct effects of GH on @entity413 metabolism and add additional benefits to pegvisomant treatment for @entity2012 .
