title: Normalisation of insulin-like growth factor-I does not improve insulin action in cirrhosis.
abstract: OBJECTIVE
  Cirrhosis of the liver is characterised by insulin resistance and low levels of insulin-like growth factor I (IGF-I). Lack of IGF-I may contribute to this insulin resistance, as IGF-I increases insulin sensitivity. This study aimed to determine the effects of normalisation of IGF-I on insulin action in cirrhosis.
  
  
  METHODS
  This article is a randomised sequence-crossover placebo controlled study. Eight patients with cirrhosis and eight controls were studied following treatment with IGF-I (50 μg/kg twice daily) or saline. Insulin action, glucose utilisation and endogenous glucose production were measured during the euglycaemic hyperinsulinaemic clamp.
  
  
  RESULTS
  The patients with cirrhosis had normal fasting glucose level, but increased levels of insulin (P < 0.05) and C-peptide (P < 0.05). Insulin resistance resulted from a defect in glycogen synthesis, whereas insulin-mediated suppression of glucose production was unaltered. In cirrhosis, IGF-I treatment normalised free (from 0.07 ± 0.01 to 0.26 ± 0.05 μg/L) and total IGF-I (from 73 ± 6 to 250 ± 39 μg/L), whereas in controls, the IGF-I level increased into the upper physiological range (free IGF-I from 0.23 ± 0.02 to 0.61 ± 0.06 μg/L; total IGF-I from 200 ± 19 to 500 ± 50 μg/L) (all P-values < 0.05). In cirrhosis, IGF-I treatment did not change fasting glucose, insulin or C-peptide levels (P > 0.05). In the controls, insulin and C-peptide levels decreased (P < 0.05). IGF-I treatment did not improve insulin sensitivity in cirrhosis.
  
  
  CONCLUSIONS
  Because normalisation of IGF-I levels did not affect insulin sensitivity lack of IGF-I is unlikely to result in insulin resistance in cirrhosis. IGF-I supplementation is therefore unlikely to improve insulin action in patients with cirrhosis.
authors.affiliation: Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus C, Denmark. nielsenm@post7.tele.dk
authors.forename: Michael F
authors.initials: MF
authors.lastname: Nielsen
authors.forename: Niels K
authors.initials: NK
authors.lastname: Aagaard
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Grøfte
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Jacob
authors.initials: J
authors.lastname: Greisen
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Peter
authors.initials: P
authors.lastname: Holland-Fischer
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015200:Fluoroimmunoassay; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D018709:Statistics, Nonparametric
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007334:Insulin-Like Growth Factor I