The insulin like growth factor system in cirrhosis. Relation to changes in body composition following adrenoreceptor blockade

Growth Horm IGF Res. 2012 Dec;22(6):212-8. doi: 10.1016/j.ghir.2012.09.001. Epub 2012 Sep 30.

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.

Design: 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.

Trial registration: ClinicalTrials.gov NCT00493480.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Adrenergic alpha-Antagonists / therapeutic use
  • Adrenergic beta-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Body Composition / drug effects*
  • Bone Density
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use
  • Carvedilol
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Liver / drug effects
  • Liver / metabolism
  • Liver Cirrhosis / metabolism*
  • Male
  • Middle Aged
  • Propanolamines / pharmacology
  • Propanolamines / therapeutic use
  • Propranolol / pharmacology
  • Propranolol / therapeutic use
  • Prospective Studies

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Carbazoles
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Propanolamines
  • Carvedilol
  • Insulin-Like Growth Factor I
  • Propranolol

Associated data

  • ClinicalTrials.gov/NCT00493480