Growth hormone, insulinlike growth factor-1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease.
The liver is the major source of circulating insulinlike growth factor-I (IGF-I) and has been suggested as a major source of at least two of the major binding proteins that modify its bioavailability. We aimed to assess the direct effects of liver dysfunction on serum levels of IGF-1 and its major binding proteins by measuring fasting levels of growth hormone, IGF-1, IGFBP-1, IGFBP-3, insulin, C peptide, and glucose in 35 patients with cirrhosis and during an oral glucose tolerance test in 16 of those patients. Serum levels of growth hormone (GH) were high in the patients: median, 12.0 mU/L (range, 1 to 87) compared with normals, 0.95 mU/L (0.1 to 20) (P < .0005) and serum IGF-1 levels were low: 81 ng/mL (38 to 153) versus 193 ng/mL (151 to 235) (P < .0001). Serum IGFBP-3 levels were low in the patients: 1.59 mg/L (0.46 to 4.43) compared with normals, 5.41 (4.34 to 6.11) (P < .0001), and there was a significant negative correlation between IGFBP-3 levels and Childs Pugh score (r = .63 P < .0001). Fasting IGFBP-1 levels were significantly higher in the patients 31 ng/mL (11 to 92) than normals, 14 (7 to 20) (P < .0001). There was no correlation between fasting insulin and IGFBP-1 levels despite high fasting insulin levels. A decrease in IGFBP-1 levels was seen during the glucose tolerance test (GTT) in all patients. In conclusion, there are significant changes in the levels of two of the major IGF-1 binding proteins that may further limit the bioavailability of already low circulating IGF-1 levels. Substrate availability appears to be a stronger influence on fasting IGFBP-1 levels than does insulin, and the close correlation of IGFBP-3 with liver function indicates a dominant regulatory role of the hepatocyte.
Donaghy
A
A
Institute of Liver Studies, King's College Hospital and Medical School, London, United Kingdom.
Ross
R
R
Gimson
A
A
Hughes
S C
SC
Holly
J
J
Williams
R
R
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D002908:Chronic Disease; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013002:Somatomedins / Q000378:metabolism
D001786:Blood Glucose; D002096:C-Peptide; D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone