title: The insulin like growth factor system in cirrhosis. Relation to changes in body composition following adrenoreceptor blockade.
abstract: OBJECTIVE
  Circulating levels of IGF-I and IGFBP-3 are low in cirrhosis and are related to liver dysfunction. Metabolic disturbances include malnutrition with altered body composition and osteopenia. Since the effects of IGF-I may be associated to changes in body composition and bone mineral content (BMC) in cirrhotic patients, we investigated the relations between changes in the IGF-system and body composition and the effects of long-term alpha- and beta-blockade.
  
  
  METHODS
  The study was designed as a combined cross-sectional and prospective randomised controlled study of 62 patients with cirrhosis. Twenty-three of these patients were randomised to treatment with beta- or combined alpha/beta-blocker for 3 months. Haemodynamics, body composition, and systemic and hepatic IGF-I and IGFBP-3 levels were determined in all patients. In the subgroup changes in body composition and IGF-I/IGFBP-3 levels after 3 months of beta- or combined alpha/beta-blockade were additionally examined.
  
  
  RESULTS
  Both the hepatic and the systemic IGF systems were suppressed and correlated with liver dysfunction and anthropometrics (p<0.05-0.001). Multivariate analyses revealed that changes in the IGF-system were determined by metabolic liver dysfunction as well as anthropometrics. In the follow-up study, hepatic venous IGF-I (p=0.05) and IGFBP-3 (p=0.02) increased after 3 months only in the group who received beta-blocker. In both groups, fat body mass increased significantly after 3 months (p=0.05-0.001).
  
  
  CONCLUSIONS
  In cirrhosis, the IGF-system is associated with both anthropometrics and synthetic capacity of the liver. Changes in IGF-I relate to changes in anthropometrics and there seems to be a differential effect depending on the type of adrenoreceptor blockade. Future longitudinal studies are needed to unravel these mechanisms in cirrhosis.
authors.affiliation: Centre of Functional and Diagnostic Imaging and Research, Section of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Bonefeld
authors.forename: Lise
authors.initials: L
authors.lastname: Hobolth
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D001823:Body Composition / Q000187:drug effects*; D015519:Bone Density; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use; D000077261:Carvedilol; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011412:Propanolamines; D000077261:Carvedilol; D007334:Insulin-Like Growth Factor I; D011433:Propranolol