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document
Acute effect of pegvisomant on cardiovascular risk markers in healthy men : implications for the pathogenesis of atherosclerosis in GH deficiency . Cardiovascular risk is increased in GH deficiency ( GHD ) . GHD adults are frequently abdominally obese and display features of the metabolic syndrome . Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well . We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions . This is a model for acute GHD without the alterations in body composition associated with GHD . We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting . In addition , we investigated the effect of pegvisomant under normal , i.e . fed , conditions . Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels ( 1.0 +/- 0.15 vs. 0.31 +/- 0.05 ng/ml and 0.86 +/- 0.23 vs. 0.46 +/- 0.23 ng/ml , respectively ) . Fasting in combination with pegvisomant also decreased serum free IGF-I levels ( 1.0 +/- 0.15 vs. 0.31 +/- 0.07 ng/ml ) . Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting . Pegvisomant alone had no influence on insulin sensitivity . The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant . Among serum lipid concentrations , only serum triglycerides increased significantly as a result of pegvisomant alone ( 1.0 +/- 0.2 vs. 1.6 +/- 0.4 mmol/liter ) . The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone . von Willebrand factor antigen levels declined significantly under the influence of pegvisomant alone ( 1.1 +/- 0.07 vs. 0.8 +/- 0.06 U/ml ) . In conclusion , in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease . These data suggest that the secondary metabolic changes , e.g . abdominal obesity or inflammatory factors , that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD .
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Intervention_Pharmacological
pegvisomant
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Intervention_Pharmacological
pegvisomant
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Intervention_Pharmacological
pegvisomant
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Intervention_Control
placebo
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Intervention_Pharmacological
pegvisomant
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Intervention_Pharmacological
pegvisomant
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Outcome_Physical
serum free IGF-I levels
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Outcome_Physical
serum free IGF-I levels
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Outcome_Physical
free IGF-I
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Outcome_Physical
insulin sensitivity .
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Outcome_Physical
insulin sensitivity
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Outcome_Physical
insulin sensitivity
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Outcome_Physical
serum lipid concentrations
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Outcome_Physical
serum triglycerides
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Outcome_Physical
changes in lipid concentrations
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Outcome_Physical
von Willebrand factor antigen levels
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Outcome_Physical
risk markers for cardiovascular disease .
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Outcome_Physical
abdominal obesity or inflammatory factors
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Participant_Age
GHD adults
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Participant_Sex
healthy nonobese males