Effects of octreotide on serum insulin-like growth factor I and insulin-like growth factor binding proteins in patients with cirrhosis.
Hyperinsulinaemia and reduced insulin sensitivity are common features in patients with cirrhosis. Octreotide, a long-acting somatostatin analogue, is used in cirrhotic patients in the treatment of bleeding oesophageal varices. Octreotide has potent effects on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis in healthy subjects. but the effects on the GH/IGF-I axis in patients with cirrhosis have been described only briefly. The effects of a 12 h infusion of octreotide (bolus 0.75 microg/kg followed by 0.75 microg/kg/h) in 25 subjects (normals n=9, compensated cirrhotics n=8, decompensated cirrhotics n=8) were compared with those in placebo-treated controls (n=19) during fasting conditions. IGF-I, free IGF-I, IGF binding proteins (IGFBPs), insulin, C-peptide, GH and glucose were measured. Insulin resistance was calculated using the HOMA method. Octreotide reduced levels of total IGF-I in patients with compensated cirrhosis (p=0.03) and free IGF-I in decompensated cirrhosis (p<0.01). Insulin resistance was significantly reduced in normal subjects. whereas the reduction in insulin resistance did not reach statistical significance in patients with cirrhosis. In normal subjects, octreotide increased the IGFBP-1 area under curve threefold (p<0.01) and decreased IGFBP-3 levels (p<0.01), but these effects were blunted in the cirrhotic patients. Similarly, the reduction of insulin and C-peptide was blunted in the cirrhotic patients, whereas a significant reduction in GH was demonstrated in all groups. The effects of octreotide on the GH/IGF-I axis are mitigated in patients with cirrhosis and this may be a reflection of relative hyperinsulinaemia during octreotide treatment in these patients.
Ottesen
L H
LH
Department of Hepatology V and Centre for Clinical Pharmacology, Aarhus University Hospital, Denmark. lo@farm.au.dk
Frystyk
J
J
Kiszka-Kanowitz
M
M
Grønbaek
H
H
Bendtsen
F
F
Flyvbjerg
A
A
D000328:Adult; D015153:Blotting, Western; D002096:C-Peptide / Q000097:blood; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D015203:Reproducibility of Results
D002096:C-Peptide; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D010919:Placebos; D007334:Insulin-Like Growth Factor I; D015282:Octreotide