Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis.
OBJECTIVE
Liver cirrhosis is characterized by reduced circulating IGF-I and this has been linked to an adverse clinical outcome. Therefore, we investigated the dynamic changes in circulating total, free, and bioactive IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binary complex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis.


METHODS
Seven Caucasian males with liver cirrhosis and seven healthy males matched for age (54.4+/-3.2 vs 54.6+/-4.4 years) and body mass index (25.3+/-1.2 vs 25.9+/-1.3 kg/m2) were studied. Blood samples were drawn at 0, 30, 60, 90, 120, 150, and 180 min for determination of serum total and free IGF-I, IGFBP-1, IGFBP-2, and binary complex, while bioactive IGF-I was measured at 0, 30, 60, 120, and 180 min.


RESULTS
In comparison with healthy subjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower, while IGFBP-1 (268%) was higher (P<0.05), IGFBP-2 (172%) tended to be higher (P>0.05), and the binary complex unchanged (approximately 100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchanged in both study groups during the OGTT. Bioactive IGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT (P<0.05). A similar tendency was observed in healthy controls (P=0.052). Concomitantly, IGFBP-1, binary complex, and IGFBP-1 saturation index decreased significantly in both groups. The disappearance of the binary complex was about twofold faster than that of IGFBP-1 (P < 0.05).


CONCLUSIONS
Despite unchanged concentrations of total and free IGF-I, bioactive IGF-I declined significantly after an oral glucose load in patients with liver cirrhosis and the same tendency was observed in healthy subjects. We speculate that the reduction in bioactive IGF-I may be related to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I.
Chen
Jian-Wen
JW
Medical Department M (Endocrinology and Diabetes) & Medical Research Laboratory, Clinical Institute, Aarhus University Hospital, Denmark. wen@iekf.au.dk
Nielsen
Michael F
MF
Caumo
Andrea
A
Vilstrup
Hendrik
H
Christiansen
Jens Sandahl
JS
Frystyk
Jan
J
D001786:Blood Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; C032231:IGFBP1 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I